Document GrOQDB9xxnJQvE2yJ1v7Dgqv

MAN VfB York LlNDBeRci Oiio Paradise D. C. P---r.J*. o Jeroi.d Ji. hOLov. Chicago. Illinois Krica H. Steinberoer AV York. New York Cledf A. Szuch Morristown, Now Jersey Rodman Ward, Jr. Wilminffon, Delaware rk, in.V. 10279. Telephone (212) 964-9400 Drawing by Chas. Addams; The New Yorker Magazine Inc . * r.Tr-*iy-1-y j: on's midyear meeting always gives time to reflect on serious Issues con, and the group's current program in LETTERS : m. a r >ed uniform state law balancing the ment information with the need to posing- ratification of the so-called and private rights to exploration and ' r celestial bodies. produces less of substance than does invention, the airing of such topics vide range of matters. A further look *ates the scope of this Interest, as the to consider proposals that would: ilative districting for state and sp ies. rged with criminal offenses to subution or sentencing. n ; the legal status of prisoners in 1 model products liability legislation, the ABA House of Delegates are not of debates. However, they show once relation is willing to confront difficultever-changing faces of society and the e Ruling i should become more commonplace ; Court has ruled that the presence of irlminal trial is not Inherently uncon- hich cameras have not been allowed rules in light of the justices' decision, le courtrooms by the viewing public, er, that the ruling will not be the final Mow that state rules allowing cameras ;ld, broadcasters should act with conlals to be shown and in their technical room arena. in* the U.S. Supreme Court will realize proceedings. Regular views of the airate to the public one of the finest exdon. Plaintiffs Lawyer Felt Outside Counsel s Whip YOUR Jan. 28 article by Douglas Lavine, "Outside Counsel Are Feeling the Corporate Whip,", hit home with me. ' . .- . .4 - V-Lv I represented a plaintiff who suf fered lung damage due to Inhalation of PVC gas at his place of employment. I; filed a workers' compensation claim and succeeded in obtaining a judg ment for occupational, disease, at least establishing the causal relationship. I then started the third-party suit against the original companies that supplied the materials to the employer. The case Involved 24 of the biggest corporations In the world. Then It hap pened as described In your article. .. I was bombarded with Inter rogatories, unnecessary pounds of them: motions for more particulars that were minute and were covered In the other answers to the inter rogatories; requests for depositions that could have taken months, to com plete and were repetitious of the answers furnished, under oath, in the interrogatories; and many ether procrastinations and delays. All by "Eminent Firms." In fact, one firm represented two of the defendant cor porations, even though all of the defen dants filed cross-claims against each other. According to my experienced estimates, by the time we were ap proaching the voluminous depositions, the defense fees could have been at least $280,000 and by the end of the case could have reached $1 million. The cost to the plaintiff amounted to $28,000. V - c..ou.. .l.d. have jj Luckily, as the case progressed my client's medical exams showed his condition was stable and not deteriorating, and thd'possible verdict might have been, under the circum stances, between $50,000 and $78,000. ..-.'V My client and I felt that it would not be worth it to make defense counsel wealthy while we were sweating to meet our expenses on the gamble of the possible verdict. Besides, if my client's condition got worse, he would still be protected by the workers' comp judgment because he continued working at his old Job under the same circumstances. We put out a feeler to try to settle, but to no avail, even though we in dicated settlement of about $2,000 for each defendant. To save ourselves from further costs, we eventually moved to dismiss the case, to the shock of the defense attorneys. I doubt that the defendants themselves were aware of, or appreciated, what had happened. Hurrah for the Inside counsel named in your article. I wish I could get that kind of work, especially because of my policy of keeping costs low for the client. (Note: A few weeks after my client's case was discon tinued, I wound up in the hospital with a bleeding ulcer.) Emanuel Geraten Newton. N.J. I0 0 I9 2 & 2 LETTERS AND ARTICLES WELCOMED THE NATIONAL LAW JOURNAL welcomes letters on matters of in terest and concern to lawyers and those associated with the legal profession. Readers are also Invited to submit articles and analyses on issues they believe warrant the attention of our subscribers. BFG39741 The equation is simple, insists toxicologist Samuel Epstein: Chemicals more than diet and cigarets -- are killing us By DOUGLAS ILKA Mmi Staff Writer ITH his thinning hair, gold-rim- Wsad cUaaaa aad professorial sir. Dr. Saaual & Epatais hardly looks the put of a na who has takes on such of the world's scientific, industrial and political communities in an attempt to pinpoint what n*Uy causes cancer. But at 55, Dr. Epstein obviously relishes his public advocacy role. Fourteen floors up into the polluted atmosphere he so desperately wants to clean up, he pauses in his "Gold Coast" apartment on Chicago's upper north aide to ponder questions on his favorite sub* ject. The answers come with meticulous precision in a British accent muted from yean of consultation with American re- Dr. Samuel S. Epstein Archer*, labor leaden and political 'vista. times, marked Dr. Epstein as an enemy of Jontrary to what some recent studies industry and swept him to national seem to Indicate, cancer, he insists, is not prominence on radio and television talk caused by nearly everything around ua. shows. He is comfortable dealing with a Instead, he says, it is caused by e relative wide range of questions about cancer, ly small number of chemical contami science end politics. nants occurring at certain industrial sites "Subversion of the democratic decision or distributed throughout the environ making processes -- this is what I am ment by such processes as industrial mainly interested in," he says, "it so hap pollution. pens that occupational issues are a good Dr. Epstein is an internationally recog cutting edge. I've used cancer in this area nized expert on toxicology and chemical as a paragon of failed democratic decision carcinogens (cancer-causing agents). He making -- basically, showing bow very * has served since 1975 as professor of occu powerful interests can manipulate and pational and environmental medicine at subvert overall democratic decision mak the School of Public Health, University of ing. This is the unifying theme of my Illinois at-the Medical Center, Chicago. interests. He holds multiple medical degrees from *Tm just finishing a book which tries to the University of London end has had 250 come to grips with the issue of hazardous scientific papers published. wastes as an expression of technology run His The Polities of Cancer was a 1977 amok -- the failure of social controls to Sierra Club book selection which com come to grips with technology." bined equal parts science, public policy Dr. Epstein describes some of hie views and white-collar crime. The controversial on cancer, science and politics in this tome, reprinted and expanded several interview: Wji BFG39742 25262001- * v. /.V WEST/ v; WAIi|;:_vt4T 96' wide $529. Co A' 13 ": * fe. Q: Dun'i a theory that own fault, this removes from smoking, diet and other industry the onus to dean up especte of a person's life* style may have a bearing on whether or not they get the workshop. It*a obvious that it is economic self-interest Then there is in the scientific com cancer. Why do you think there has been such empha sis placed on this theory? munity a group which does not 'necessarily have any economic investment, but they have an intellectual investment to the theory -- people in the last 10, A* The role of lifestyle has beta grossly exaggerated as part of an industry strategy to minimize die importance of exposure to occupational and environmental carcinogens. Industry, for many years, has been evolving strate 20, 30 yean who should haveknown better but somehow got boxed In to the exclusivity of this theory and ignored the whole importance of occupation al factors, and they art caught with their pants down. gies to prevent regulations. One <fc What about clgaret smo* . is the control of information and *TXking?^ -f- .'% ; ' another is the denial ofrisk. The f.. third element is: Blame the vic- A* There is a group ' of scientists tim. If you get cancer; it*s your who rightfully believe that own fault You drink too much. , tobscco is a very important You smoke too much. The life- . cause of disease, mortality,; mor ' style theory shifts the burden from industry' to the individual bidity and lung cancer -- which I couldn't agree with more -- Q: Who has been pushing the theory and why have they been pushing it? but they've overemphasized and exaggerated the role of tobacco to the extent that they are basi cally excluding other causes. If A* If industry maintains that the worker gels cancer, that it's his Gumtimmd M Nett Pag* U :v, ji he a 693 ftV'Y' "v. J BFG39743 Z00Z9ZSZ Cancer CwumW/ifw fncr^uv fta* you /oo* it tiie wbofe history ot tobac co, you have something like 23 retro spective epidemiological studies associ.sting cancer and tobacco, but for ah intents and purposes none ot these inquire into the role of occupation. This is ah extraordinary omission.r Q: What about diet? A: There really isn't any scientific basis for incriminating diet as a major I'lustf ofcancer, Q: The American public is being deluged with daily accounts of cancer being caused by such com ; _ mon substances as coffee and saccharin. Does everything cause : cancer? A: The number of chemicals that cause cancer are very feat and far between. We only have epidemiological data on about 24 or 25 chemicals, the chemical agents and processes that have been . shown to induce cancer. The idea that everything causes cancer is very far from the truth. Cancer, a carcinogenic twayuinnunl, unique pbenom*. not Q: How can you say it is a rare | ^ occurrence when one out of four, ' Americans will get cancer? -**w.'*j A: That's not what I said. The number of \ chemicals that induce cancer are very rare. That doesn't mean to say cancer is rare. The ability of chemicals to in duce cancer is very, very exceptional ] That's an. enormous difference. Q: What then. In your view, causes cancer?.r*\-*'}%& A: I don't think there is any question that I exposure to chemical carcinogens in the environment is the cause of the over whelming majority of human cancers. Less than 500 chemicals, in total, have been shown to induce cancer in ""*** { .. .. in tests of hundreds of thoueands of ' chemicals +y: s, *'.y: *" : 3- 'iS,0: i < V- Ii fa % f *. ' -ir m __ ep p ____ "5.--______________________________________________________________ _______ '$S$r --"=-^. y.-:Zr ,,/' .. ~J0*, . -V iX? fjf .vr, y 7*--.---i'tsht-tvidh .... /> '5sir5=r-;; 35*3| A' Iw-iuU 25262003 BFG39744 Q: It there e safe limit that : een he established for human exposure to. a careiacB? . A No, that's completely nanaeasical We just don't have sny'ssfe ' trenched establishment both in the National Cancer Institute and elsewhere -- iras such to basically defy attempts to shift funding from one area to more relevant areas ofresearch, limits for chemical carcinogens. . Q: What about Interferon, the '' figures of parts per million or ; ' so-called "miracle cancer parts per billion are yery mis* drug"?. leading. They give the impression these ere small amounts. They are not They are enormous amounts. There are a wide range of carcinogens that have been shows to be active at the hwest levels tested', and ... these levels go down to parts per billion and parts per trillion. A Interferon is one of the classic boondoggles. The American Can cer Society has spjot millions on the basis of very unsubstantial evidence. After spending 41$ millbn in research, then is a realisation, that Interferon is not the miracle drug-- it isn't going. Q: For 20 years scientists have tried to show that can- - cert are caused by viruses. With few exceptions that theory has proven, falsa. Why? to make a substantial difference in curing human cancer*. In fact most cancers prove resistant to it after a shot period of time Interferon is`programed to be a valuable and useful product from the point of view of the A While it was clear by 1974 that this Use of research was poorly profitable, the power of an en pharmaceutical industry, but for the cancer patient as signifi cance is marginal. m-- - Exposure to nude chemicals is a leading cause ofcancer, according to fir. Epstein. 3I u =--. . .S' ;____ * -'I ' 1 V' w 11 JLM. TO !: 1 ** fk'^4 6 P.M. - Here's an IMF tumteon at rk is Hu time prices you** w? AS our buyers beta slow me . . not pern* HOPING fat i * Per peeertj mcterTSherf to tbs store, ouctttosef k wiftxn. .- onm debt! S0FA4CHA v- toe numbers. Jtr: 1aS( ugly! > AMO ON THE we'S Me to reason nr tit Bum's a bru , . . it's cewr pretty she tt youne* t be - mate to ssfl " EMOOMSU '* plans . .. m ... >*>; pltttt. ptMM 3^2. at bm I---** to set*... v UNITS. you Mi them tor > you ctnl see . as $39 and up tt your uii r and SAVE *570 will be our Dining At them up tor i Suite tor Just spring Is 25% ROOM suites whole set or. from eonttow 8am out 11 4 We hope by i COST--when t on by wo IOC A FACT--tOU i As another ex mute lot U soboefton of s K, . ,,,,. : - V_?Y.2- LIMITED - - TtffiL ''i* C G UVONIA Ope i :*? 25262004 BFG39745  T-VrW *iy-*&* Cancer rw>urrf/Am Awf^V^V V A: Oat, m straight presentatioa of the Q: You seem upset with the way . facts. Another is interpretation of the ' Americans handle the cancer - situation. Why don't you return to ** EaflAsd? ' *" .1 tacts. And a third is investigation of,} the facts. These are all different roles, which different newspapers perform 'A: I dldn t uy / was upset I'm politically prestostic. In America at least you ' h--a--v--e--an open s--y--s-tem. I've -just coba,- with different degrees of skill end 7: expertise. In ay personal experienca in the last 20 years. I've found the news* papers in this country have been re-.; pitted a British edition of my book, m nr- gponsible for more important advances which I've pulled out all the American in public her'fh than the overwhelming stuff on regulation and legislation and majority of the scientific community added about 200 pages on the British political scene. From the point of view put together. In no way am l arguing against scientific research. I'm saying of policy and decision making, it is we have to "tuch information that is vastly inferior to the American scene. not being used appropriately that the Q: Can you five a few examples? key issue is implementation ofinformal tion as opposed to the need for more . A; They have a very strict libel law in scientific research. - ;- 7;-^ : England. You couldn't function as you Q: That view is not going to make do ss reporter. You'd be in jaiL They>. y0U popular among your peers, have an official secrets set that covers v* - such thinp as the amount ofchemicals A: Popularity was never one ofmy objec discharged by industry in the local tives. ' waterway. Bureaucrats can't be called into account before a congressional Q: How about their respect? committee. A: In genera/ / think / have the respect of Q: What effect will the Reagan administration have on cancer' reiearcht- - . the scientific eommunuty. In the 1960s / was respected scientifically, but peo;?ftie were made uncomfortable by my A: 1 think as far as the Netional Cancer^ ublic policy. Sow,. IS years later, I Institute is concern*, there wOlpirt-W^ ` ** ot^n!a CaU otp*bUe ably not be any major cutbacks. But 1 ' think the effects, in spite of that, are going to be quite devastating -- partic- policy. It's difficult to be too critical of * ma scientifically. It's a tittle difficult to write me off. ulsrty m reUtron to Q. How do you *n.wr critic, who cer tnd douse m [enenl Tbt Beys* ' ,re Uit , meSaIom*niac .drmnetreuen. mthout eny quKtwn. . ,, who Ukec.to bc ia the prew, who Byc^toanpascW/wJftnetcc.t- ulcM to ^ on xv wpho enjo fboernoecfict uapnsatliyosnis* eberafosruereasn.y re*gulations . *\,m *.iv ' Wi* v f- . . ..'Jlfe I ' 1^4 ' ;r'7''5 .Q: What's wrong with cost-benefit' A: That isn't a very serious question, be-v analysis?. cause essentially what I am saying now . A: It is very misleading. It emphasizes the immediate cost of compliance and uses - ' data from industry; in many cases these data are grossly exaggerated, . while employes are overlooked. It bal . ences these egeinst the so-called. benefits. The benefits of regulation, \ unlike the costs, ere delayed 10, 20 or is whst 1 was saying in 1965, when I was selling nothing. The reason I wrote the book wes to limit the demands on my time. I could have spent the rest of my life wandering around as an /father-. ant spokesman for the public interest community and for scientists who be lieve in the prevention ofdisease. 30yean from now. It's very difficult to < . get an estimate of the number of lives * that will be saved 20 years from now.] . The whole cost-benefit analysis has, - evolved as the modem strategy of industry to block regulation. I think ve. are going to see a massive dismantling of .the whole occupational regulation apparatus. i cW. - 7% ! ' ^`7^777 ' . >m -.. Q: Many professionals criticise newspapers for printing articles _V about uoexplained clusters of cancer incidence. They say news^ papers shouldn't pretend to be scientists. What role should newspapers play? * JW?*1 %r 25262005 BFG39746 results of exposure of rats, hamsters, and mice to vinyl chloride. Ann N'Y Acad Set 1975; 210:219-220 21 Lee CC, Bhandari JC, Ilause WB. et aL Inhalation toxicity of vinyl chloride (VC) or vinylidine chloride (c (VDC) In rats and mice. Pharmacologist 1976; 15:243 22 Ilofmltcrg B. Ttoncvi T, Wind! M. Tlte pathology vinyl chloride exposed mice. Acta Vet Scand 1976; 1 328-342 Pulmonary Manifestations of Vinyl and Polyvinyl Chloride (Interstitial Lung Disease)* - Newer Aspects E. Af. Cordasca, M.D., F.C.C.P.; S. L. Danclcr, M.D.; J. Kcrkay, PU.D.: II. S. Van Ortlstrantl. M.D., F.C.CJ'.; E. V. Lucas, M.Dj T.Chcn, Ph.D.; and J. A. Gotish, M.D., F.C.CJ Newer varieties of occupational lung diseases primarily due to the vast Increase In Industrial technology have been reported recently. Preeminent among such newer agents are vinyl chloride (VC) and polyvinyl chloride. Very few cases have been reported, in Europe only, with descrip* tive histopathologic changes. To our knowledge, no path ologic studies of VC exposure have been described in the American literature. The biopsy abnormalities in our patients disclosed desquamation of alveolar macrophages into the alveolar lumina and minor interstitial and alveolar inflammatory changes. Pulmonary function ab normalities included restrictive insufficiency. Preventive therapy consists of the avoidance of further exposures, frequent industrial hygiene monitoring, and total avoid ance oftobacco smoke, as well as associated aimospheric pollutants. Thus far, none of these patients has exhibi ted evidence of pulmonary neoplasm. All three patients survived their occupational injuries, and two are still disabled to varying degrees. Urine and blood levels of phlhalic acid derivatives were elevated in two patients, the exact significance of which is not fully known. It probably represents a toxicologic response, but must be further pursued before conclusions can be reached. 7VT ewer varieties of occupational lung diseases have ' Ik-tii rc[X>rUHl recently, primarily slue lo pro found advances in industrial technology. Preeminent among such newer agents are vinyl chloride (VC) For editorial comment see page 826 and polyvinyl chloride (I`VC). substances used ex tensively in the plastics industry. More than 18 bil lion lbs were produced in 1972, with approximately 25 percent produced in the United States., 36,000 and 50,000workers were exposed at! tknrrgroctrcs or (luriugThe processing ie numler of people exposed, owing either to alteration of the finished product or de- *Kmn (lie Cleveland Clinic Foundation ami Cleveland Slate University, Cleveland; and Northeastern Universities School of Medicine, fluvcnna, Ohio. Manuscript received August 29; revision accepted January 29. Ncjirint requests: Or. Conlasro, 0-VX) Euclid Ac-cnuc, Cleve land 44106 828 COROASCO ET AL BFG39747 struction pf these products, or amply to living near plant where any of these diverse processes may t=l place, is unknown. H^^c^fTcwdcncc has been pn CAccort !maronmental Protection Agent report, approximately 90 mOlion .kg of PVC at discharged annually into die atmosphere.2 The emergence in 1974 of VC as a new occupt tional carcinogen, producing angiosarcoma of th liver, focused attention on other toxicologic maniftf tations of this group of chlorinated hydrocarbon; Pulmonary effects were first described in 1970, bu few cases have been reported characterizing lb histopathologic changes of the human respirator tract, all published from abroad, paboits wit ` famer ot either.VC ukbnuuMJr o__i__P_V_C t. ie___ _ KSpctttei!!' Lung liiopsy results anti'the implication ~"rof their exposures arc discussed. In addition, ultramicroscopic findings are included, and new bioch< mica! analyses are reported in two patients. -A summary on this subject of PVC-itwluced disease was presented by the authors at a symposium in tlic Soviet Union in October. 1978.* Materials and Methods Our experience involves the diagnosis and management rt - .ACTuawumii ni Alt.tinu. yjttenti 'Siial. am! one by open tnethiM Pulmonary function studies were done by the System* Research Laboratory method and included total vital capacity. timed vital capacity, flow rate, and diffusion capacity with carbon monoxide. Arterial blood gas determination* were performed by the Instrumentation Laboratory method, ami distribution studies were measured with tlc pitrnjx0 washout method. Routine screening tests included complete blood (GUO). urioalysis. serology. SMA-12 chemistry I'1'1" liCGs, am! sputum studies for routine bacteriology- ->*uelrt and cultures of sputum for fungi and Mycobacterium wcre also performed. Each patient also bad a sputum cytolof^ examination. Imnuimtlogic testing was performed on C3 patient and is detailed under the case discussiou. CHEST. 78: 6. DECEM8ER. 19$ , ... , A oo-yc-ar-UKi uuu all / ,hi>- . iiNliny III UNlftk 17; I mOntfr-hfrtory of .rcssixc dyspner? * cyanoaifc-At the present time the cough is dry. 5 . nntng h* paroxyx/ns; it may lie initiated liy breathing jcply or changing positions. Medical history, family history, travel history, anil review I jjjterns were noncontrihutory. She had never smoked of <I any pulmonaiy symptom# ui^tU4fn* ' " " " ' " ". "twf-prrisrwt --i -- " ^ patient has heen employed asa 1 nit ficoRE 1A. X-ray of chest Diffuse nodular pneumonitis. Ik* TV Ilf n UK :tu- A <c* u* if H- r fy.uiiE 1B and 1C. Diffuse fibrosing pneumonitis with intcrititial thickening and desquamation of cells into alveolar bnion. / . ,........................ ** < Mk-al'j. worked with adlics-.e laf lamping during tlie past year. She has never experience cough or shortness of breath in relation tiThcr worirTxpnsnrr. However, stK:~(lnrvr\<4ate that her.fatigoe is more profouml as the week goes on and tiiat each Sunday niglif is her best time. 71m fatigue has lessened nmv tiiat sIm- liinils Iter work to two-day (icrimlx, PhyxtcaJ- ` examination results were normal, except fi^. hamtt^fe^-Weie fine^iiiq^ratory crackles heard dUrM.w:ly'V' oveT^3pMRficId.O>ut RWKe proniioenllyat tfic bases. Ther** were nd wheerei^llT fThgefs'khowetl duhhing; this appar ently [till nfvtirreiTmrr I lie last six mouths. Her |<k-x were normal. Lalmratory values, whieh were nonnal, included CMC. liver and renal function tests, urinalysis, and EGG. A hyper sensitivity sensii for various fungi was negative. 71v sisli- mentation rate. Jatex fixation, rapid plasma rcugiit (Itl'lt), antinuclear autilHKly (ANA), ami Clq were all nonnaL Circulating immune complexes hy Clq-hinrling assay were negiitive. 71k* lympluKyte lransfortnation lest against 1*V<! was also negative. /TW- chest x-ray film revealed diffuse retieulrmodular changes. Doppler ultrasound examination of the fingers deiiMHistratcd tliiTrasrtl IiIimkI (low, more pro- ihmmkviI after cold es|Neuire. Fulnuinary fiuictaui stmly dis closed a restrictive abnormality (tlie vital capacfty-was 61 pmwt ol predicted normal );* Midi a diffusing capacity (l)l)n) of 11.2. Other iiew Icstxjndiiilcil Musi level fur tlie measurement oFphthalie acftl derivatives. namely | ^ phthalic -anhydride, a decomporfSoo product-of PVC. whkfa^ * measured 62.8 ng/mfj wfjidvb considerably^ cIeyatrc|J,llS^ urine test for thermoplastic preiduets revealed a remai elevation of two components--the pMhalit anhydrrfcdcriva-- five dicthylliexy! phtlialatl* known as DK1IP. and anothe^^ component that has been unidentified to date and b proliakly 4 a fatty arid ester, 71ii*s* lists were (M-ifornM-d at tin* Cleve land State University* Biochemical Laboratories. It b die opinion of the biochemists that these levels arc significant and have Irccn demonstrated in animal studies using PVC hilling wlu'ii tlu* E factors are at a range associated with tin: release of thermoplastic resins and derivatives. This aspect of the study is still lieiug assessed, ami a future report Is planned for publication. ' It was tluiught that interstitial fibrosis accounted for the patients sipis, symptoms, and ialxiratory abnormalities. It was further Drought that she also showed signs of PVC exposure hixieity with digital angiitis. We postulated that (he interstitial fibrosis may liave Ikw inducs-d hy her PVC cx|xistirc. Accordingly. sIm* underwent an o[h:ii lung biopsy of the right lower lain* for pathologic confirmation. An x-ray film of (Ik* durst disclosed a diffuse iHKhdur pneumonitis witliout localized disease (Fig 1A\. There were no- pleural or hilar abnormalities. Light microscopy (Fig 111 and 1C) demon strated difftisi* fibrosing pneumonitis with prominent terminal hmiH-liitilar cell Iiyprrplasia of the alveolar lining or desqua mation. liUMtmni(Iiiurrs<viicc was m*gative for compliment and immunoglobulins. Large numlrers of alveolar macro phages containing phagm-ytized material of undetermined composition was wen on electron microscopy (Fig 2). All cultures of lung tissue were nc*gative. Tlie jgx-vial Mood nml urine studies for tliennnplastie resins were pivsitive and will lx* fnrtlK'r pursmrl. `tin* patiirit was discliargcd uvetviiig 40 mg of prednisone per ilay. Comment: 111is patient s!Mlwed nonspecific signs and symptoms of filuosing iultrslitial piMumonitis, which was ZOOL9?.S2: * CHEST, 78: 6. DECEMBER, 1980 l f PULMONARY MANIFESTATIONS OF VINYL ANO POLYVINYL CHLORIDE 829 BFG39748 Figure 2. Alveolar macrophages with phagocytized ma terial (electron micrograph). confirmed by biopsy specimen. Tliere was apparently no evidence of a hypersensitivity reaction either by history (type II), lalxiratnry (type IV), or imnuinopathnlogy (lyjjcx II or lit), according to tin* criteria proposed by McComh4 as a modification of the Ceil and Coombs classifi cation. Digital angiitis, as demonstrated here, can lx; a manifestation of PVC toxicity. sponse, and later, corticosteroids (for suspected cocuwctiu tissne disease) with a favorable response. He returned to work after two weeks and again notice: m>-algias ami arthralgias, easy fatijsihility. exhaustion tnucf the end of the day, and stiffness in his joints. He was refeneJ to this institution fnr.furtlier evaluation. For tlx* jvajt^bl years he had lxx*n employed in tin* drn!x mold industry aii<nr:tcH*xtcmive daily use of VC spray pair: Review of systems, family history, medical history, and expsure history were otherwise negative. He had smoked hulf pack of cigarettes per day for the GiTRve'yesr*. Tiinitial physical examination result* were nonnal.Thc tin-* were clear. A rheumatology consultation revealed no exs* <I*iMv of connective (issix* disease, lalxiratory amt : genographk* examinations were positive for osteoarthnt:Nurinal or i*galive Lilxmitury test* included an KCX1. sene. T-,, X|. anti-thyroid binding gloltulin, VDRL, jedimentaties rate, latex fixation. IX cell prep, ANA, urinalysis. C8C. SMA-IS, and sennn protein electrophoresis. The chest x-ra* film showed diffuse, small, interstitial, and nodular dcnsit:i` ixxiltenxl tlinxiglbuit Ixilli lungs. The (latieiil returned In work. His symptoms were sljl'-r over tin- next two iiuuitli*; however, hni days Ix-fore h> admission, he complained of a "flu-like" syndrome, with a: increase in his generalized aching, a slight, dry congh. a" increase in shortness of breath, and chest tightness. On examination lie was afebrile, with few bibasilar crvpta.Bt rales and a palpable lymph node in tlie right supraclavicular fossa. An imiuuiMighilxiIin elcetniphorcsis now sluiwcd iurrvaxed IgA (330; normal. 150 :t 92), low normal IgM (5L normal, M5 105), and decreased IgC (950, normal. L-***" 255). Tlie remainder of lalmratory and physical examina- Case 2 A 4?-ycar-old man complained of "not feeding well." For tin; past 3S year* lx; had experienced vague feelings of not lieing in good health, with weakness, fatigue, diffuse arthalgius, and myalgias. In the last eight montlis he had noticed an accentuation of his symptoms as wed as dyspnea on exertion, wheezing, and a productive mnming cough. A diagnosis of asthmatic bronchitis was made at that time, and he was given multiple drugs without improvement. Three months before referral, he was hospitalized at another institution for further evaluation. A bronchoscopy was nega tive, and transhronchial lung hiopsy of the right lower lolte was reported to show, pigmented macrophages in the air spaces. Hie chest x-ray film showed increased interstitial markings. Sputum examination showed moderate WJlGs and alveolar macropliagcs. Lalxiratory test results, which were normal, included latex fixation, ANA, VDRL, F.OC, and sputum cytology. Scrum imimmoclcctniphorcsis revealed de creased IgM, slightly decreawd IgA, and normal lg(J. Pul monary function studies showed a decreused I'aO. with small airway disease. An exercise tolerance test was performed ami indicated that the. patient was capable of moderate exercise. He was given hronclifxlilafnr.s ami antihintii-s. with no re Ficunc 3. Thickened alveolar septum with accumulation f mononuclear c<-lls. alveolar m.icrphagcs anthracotic V*R' incut 830 CORDASCO ET AL BFG39749 CHEST, 78: 6. DECEMBER. 1980 changed and was interpreted hy fhe(, i/^ .'lassifiraliiMi as (iing 1/1. On biopsy. the lymph node showed histiocytosis consistent with chronic inflammation. He underwent a . trephine lung biopsy, whicli was rcixirtcd to show large | cumbers of alveolar macrophages in die alveolar air spaces. I Sickening of the peribronchiolar connective tissue, and altrol-ir septa with accumulation of iMoiHnnieltrar cells and I jiithracotic pigmentation, hypertrophic bronchiolar epithe( limn, and macrophages containing f;rn<- nnuiiints of lietitn- ederin and a few anthracotic pigments (Kig 3). The patient was discharged receiving corticosteroids, with fs.ltial clearing of his syniplnnis over the next 2Ji years, follow-up laboratory examination results have remained un changed. The chest x-ray film has remained abnormal. Comment: The biopsy specimen showed changes con sent with interstitial fibrosis; no immunologic testing was performed on the tissue. This patient differs from patient 1 in that his exposure was to the VC-mononKT as opposed to PVC . fumes. /*" Ccse3 This 55-year-old man was exposed to PVC dust during a ......... .......... / was-ajiionsnuiker. His initial exposure H-i-iiro-<l over a tn sii-wirfpWixlp(4illiii); in the development of continuous and progressive dyspnea of approximately ten days* duration. He had severe dyspnea In / the 2 t-lionr |XTid licfore admission. ______ ___________ Air sam^Ies^of>PVC- in tKeSmmediate operational area < varied hetv(ieen<200 and 315 parts'j^er million. Examination of (' tin- clicst slwivcnl liilusilir nMpi', inspiratory, crrjiitaul , ^ rales. Because he irntUHjrfailed-fo respond to oral aminophyl- lire- tli.-r:ipy piesi*ril>ed by bis Iim-iI ]itiyNiei;inw steroids and bigli-llow oxygen with a Venturi-type mask were added, with ` considerable subsequent improvement over the next 48 to 72 lumrs. Tln-n- was a gradual reduction of tlie steroid dost* over the next two-week period as the patient showed progressive improvement. Concomitantly, there was complete resolution of the roentgcnograpiiic lesions. The pulmonary function tests in tliis person disclosed a moderate rerluction nf vital capacity and in the mid-expiratory flow rates and moderate impair- mont of diffusion capacity to 12.8. The arterial PaO. mea sured 60 mm Hg at room air. The remainder of the routine lalioratnry studies, whicli inctnd<-d an SMA-12 diemislry profile, urinalysis, serology, and CBC. were normal, except for minimal leukocytosis of 12^00 cells. Figure 4b shows his chest x-ray film at the time of the six-week exposure. The histopatliologic changes wen* compatible with a desquama tive interstitial pneumonitis. The section of his lung biopsy disclusing these findings is shown in Figure 4a. ' ^ Figure 4A. Chest x-ray film ahnormality; interstitial infil trates. ficUHJE 4B. Desquamation of cells into alveolar lumen. Discussion* Vinyl chloride (CH *= CHC1) is a monomer used ajLJh-clffrrnitsil intemurdinto in the polymerization of l^VC resin ill the production of copolymers such as ^Cran^nrfas a solvent.* i^Cmonomer under normal temperature and pressure is ijjjus (111* I3.S C). It readily polymcri*/x* under pressure at a temperature of 40 to 70 C to form PVC, a white, solid material. Altlioiigli tin* polyinerizakion process was discovered in the I800s,, I*VC production did not begin in the United States until 1928.* The list of materials made from PVC is extensive ami includes foils, films, tapes, tubing, fiber, cables, artificial leather, foam rubber, paint, varnish, toys, and automobile up holstery coverings. The acute, toxic effects of VC gas ( anesthesia and narootie-eiFect) were quickly discovered and were thought to represent the only toxic effect of exposure until 1949, when Trihukh et als in Russia reported a hepatitis-like effect following long-term exposure. Other toxic manifestations were reported during the 1960s (Tabic 1), and in 1974, the association be tween VC *x|>osnre and angiosarcoma of the liver was made. Further toxic manifestations were discov ered during epidemiologic studies that were performciMxjth on production workers and on popula tions living near the plants. The clinical spectrum of PVC-induced toxic organ damage is broad (Tabic 1). The most widely reported manifestation is a sclcrodcrma-Iikc syndrome, and the most widely dis cussed is the angiosarcoma of the liver. Table 2 lists 5 CHEST. 78: 6. DECEMBER. 1980 ij PULMONARY MANIFESTATIONS OF VINYL AND POLYVINYL CHLORIDE 831 BFG39750 252G4004 ( i C< Table 1---Toxic Effects tt/ VC and PVC Exposure by Organ System Organ Toxic Effect(s) Itefcrencv(s) Liver Hepatitis (elevated enzymes) Ifejialomcgnly or abnormal liver Kean Hepatic fibrosis Angiosarcoma 30,31 31,32 30 30,31 Sktu Dermatitis (resemble* scleroderma) 2,2*1 Vascular Digital angiitis (resembles Raynaud's) 3,29,30 Hematologic Thromtjocytopcnia 24,29 Skeletal Acroosteolyxis 3,29 Pulmonary Acute airflow nledruetion Chronic airflow obstruction Interstitial fibrosis 4,22 6.7 21.22,32 other manifestations of PVC toxicity. Other than the acute narcosis, the diseases on this list were discov ered by epidemiologic studies and were thought to represent statistically significant association. The teratogenetic effect applies to communities sur rounding PVC production plants. _Tin* effects of VC and PVC cxixisnrt: on tin; pul___monary-system fneludiTboth acute and, chronic au~ flow obstruction. "Meat wrappers asthma" is a syn drome of acute bronchospasm due to the inhalation of PVC fumes from melted plastic wrap. It closely resembles an acute hypersensitivity response that can be seen with other industrial exposures, hut no documented immunologic complexes have l>ccn re ported to date,7 with one exception: a report from abroad.* Decreased flow rates are also seen with chronic exposure. One study found a decreased FEVj/FVC ratio in 30 percent and SO percent of nonsmokers with one to 20 years and more than 20 years of exposure, respectively.* Another study found decreased flow rates in 50 percent of PVC production workers who were older than 30 years.10 Others have disputed such claims.11 We have re cently encountered three patients with PVC-in duced asthma. This is the subject of a separate . report17 Table 2--fionorgan System Toxic Manifestations of VC and PVC Exposure Effect Acute narcosis Kcfcrriire(s) 33 Increased moHalily Increased cancer rate* 10,3-1 (0,13,15,10,35 Chromosomal abnormal!! ics 5,30,33,39 Increased toralogrnirily and fetal mortality 35,37.40 The risk of pulmonary neoplasms may also U j higher in VC and PVC production workers. Anitiul 1 data are highly suggestive,**-** but the standardize! < mortality ratios (SMBs) vary from 112,** 156u" ; 160,1* to 168.'* and other studies could find ** increase in the expected amount of cancer.*2 ' Another study supports a carcinogenic effect be- 1 cause of differences in expected cell types (with no ' increase in the total number of lung cancers).3 h* 1 addition, the effect of concomitant cigarette smoky? j is unknown but probably additive. Other industrial exposures (eg, asbestos, chromium, and chloro- metliyl ether) indicate a probable synergism in cat* cinogenic effects. The cell types of lung neoplasm* . reported by Waxweiler are shown in Table 3. Interstitial fibrosing pneumonitis due to PVC <*c | VC exposure has been reported only rarely.*** primarily from the foreign literature, although noduIar infiltrates on chest x-ray film have been described in 3/37 workers in one report.*7 Of 985 workers * another study, 13.3 percent showed a similar aln#** mality (1/0 or 1/1, ILO/UC classification).*4 Inter stitial changes have also been delineated in experi mental animals.** We rqxrrt three further cases of histological!* ' proved interstitial fibrosing pneumonitis in patient* exposed to either VC or PVC fumes. Signs, symp toms; and laboratory' abnormalities 3ondt cliffr7 ~signiffcanHy in patients with interstitiaftliseasc ass>*ciat'cd~ with VC~oFTVC~cqpbsunrfrom-those-u'itl* - ^idiopathr(T ihterstrtiaI fibrosisTClsuaI~syTTiptorns in- j elude the insidious onset of dyspnea, exertional weakness, and dry cough. Physical examination re veals fine bibasilar inspiratory crackles. Other sip** of PVC toxicity may be seen as welL The chest x-ray Table 3--Lung Cancer Cases Histologically Confirmed Among Cohort Workers Exposed to Vinyl CJtlaridefPolysinyt Chloride** Case No. Histologic Diagnosis Ape at Death, Exposure, Latency, yr }T yr 1 I^irge cell undiflrrvntl-ilcd 39 14 15 2 Large evil undifferentiated 40 13 IS 3 1-uge cell undifferentiated 52 22 22 4 Large cell undifferentiated 6t 1G rr 5 Large evil undifferentiated 61 8 17 6 Adenocarcinoma 45 19 19 7 Adenocarcinoma 57 12 12 X AdciUM-ar.-iitonci 72 15 *> 6 Mesothelioma (?; |nwsibte. ir patient) ... 12 JS 25264005 I I i 832 CORDASCO ET AL BFG39751 CHEST. 78: 6. DECEMBER. 1980 Ni l Jm-shows diffuse reticulonodul;{ .fiY~ tes; pulmo- 'I 1 nary function testing demonstrates a V* ..irictive pald (jrn and depression in the DLco with variable levels n . of 1'aO*. Lung biopsy specimen discloses interstitial 0 < infiltration with mononuclear cells, fihrosis, alveolar | hvpcrplnsia, and desquamation into the alvr-olar 1 lumina. Diagnosis is best confirmed by lung biopsy. 1 | At present it is highly presumptive, but strongly ' indicated, that there is an association between the ^insures and the development of interstitial fibros* iag pneumonitis. No cause-effect relationship can "citegorically be proved with certainty in such a small series. However, the patient with a history of ; . ^jiosnre in the polymerization pnK*css coupled with flie clinical studies of oilier authors (Lilis. Melon!, and Szendc) almost certainly substantiates the diag' : posis. at least in the one patient. The mechanism of the response remains specula tive, although a dysfunction in the immune system is ; probably implicated. Of 320 workers in a VC poly merization plant, 28 were found to Iiave Raynaud's phenomenon, and 19 of the 2S were found to have circulating immune complexes.* Circulating cryo- # immunoglobulins are found in 41 percent of patients with usual interstitial fibrosis and play an ctiologic role." In addition, markers of abnormalities of the immune system (ANA. latex fixation, sedimentation rate) are found in approximately 25 to 30 percent of patients with fibrosing alveolitis.** It is tempting # but purely hypothetical to speculate on an immuno logic basis for this response, despite the total ab sence of these markers in our patients. The other ) mechanism is toxicologic, namely, dose-effect rcla( tionship to exposure. * An his review of idiopathic pulmonary' fihrosis, /`Crystal31 points to several "dues" in attempting to answer the question "What triggers the disease?" * Some "triggers" (or etiologic factors) found in pa; dents with interstitial fibrosis may indude: (1) in fection (25 to 40 percent of patients antedate their illness to a viral chest syndrome); (2) hereditary factors (familial clusterings and relative increase in HLA-12 and HLA-29); and (3) cell-mediated im mune reactions (directed against lung collagen). /Perhaps toxic exposures eventually will find their ; place in this list as more associations of the type we have just presented are brought to light. - The identification of diethylhexyl phthalate (DEHP) in the serum and urine of excessive * amount (190 times'that~of~the-contr6l) in one pa tient is interesting and presumably significant. Re cently, similaFelevations of the substance in both jenini and urine were identified in the second pa tient. The substance is a decomposition product of PVC chemically similar to dicyclohexyl adipate. It --------------' f accompanies dicy<L..,iex/r dipate, a major emission during hot-wire cuttiug-i/i meat wrap plastic, as another plasticizer present in PVC. It may also occur as a (hxximposition product during the adhesive stamp-labeling process. The major ingredient of the latter process is dicyclohoxy! phthalate. Four major thermal decomposition products of dicycloliexyl phthalate are cyc!o!iex:uiol. dieydohexyl ether, phthalic anhydride, and cyckJhexyl ben zoate. The presence of these compounds, along with DEI II', was readily demonstrated in the serum and urine of two patients. In addition, urine samples also contained significant amounts of MEHP (monoetliylliexy! phthalate)-. phthalic add, !x*nzoic acid, and O and P-hydroxy l)cnzoic add. These urine components are probably metabolites of DEHP and other plasticizers present in PVC. Complete evalua tion of the metabolism of decomposition products of PVC in man is presently being pursued at Cleveland State University. Treatment is primarily prophylactic, with imme diate removal of the affected patients from the of fending fumes being of paramount importance. Corticosteroids may be helpful in the treatment of the early stages of this disease. Other immunosup pressive agents have not been used, to our knowl edge. Tim efficacy of steroids was verified in one of our patients and is highly probable in our second patient who had long-term expostire to PVC fumes. The use of other immunosuppressive agents has not been reported to our knowledge. Prophylactically, frequent industrial hygiene monitoring is of utmost iiii|>ort;mcc for the early detection of abnormal at mospheric Icvfls in the occupational environment. Close medical surveillance of such persons exposed may prevent the occurrence of severe adverse health effects. Conclusions The awareness of newer hazards of chemical sub stances iucnsisingly present in our environment is of paramount importance to every employee, as well as to the entire community, because of the obvious occupational and public health implications. Exam ples of such newer agents have been reported. N<*wer biochemical studies of both the serum and urine, notably decomposition products of thermo plastic resins of the phthalic acid group, were ab normal in two patients. The total clinical significance of these factors is yet unknown and will be further pursued^ This is one of the first reports in this country to delineate the lustopathologic changes of the respira tory tract that constitute such excessive exposures of the VC/PVC group. Therapeutic implications in clude the necessity of earlier medical surveillance as CHEST, 78: 6. DECEMBER. 1980 PULM0NART MANIFESTATIONS OF VINYL AND POLYYINYL CHLORIDE 833- soothe?: BFG39752 Ci well as the institution of diagnostic and prophylactic PCX' production workers. Environ Health Penpect I9CY. ' industrial hygiene procedures on a more frequent 17:167-70 basis. This is of paramount importance, since VC and PVC are toxic agents. Therefore, it is of utmost significance to institute such close medical surveil 20 Duck DW. Carter JT, Coombes EJ. Mortality study at workers in a polyvinyl chloride production plant, Ln.rt 1975; 2:1197-99 21 Falk H, Warwciler R. Epidemiological studies of vinjl lance to prevent serious adverse health effects. chloride health effects io the United States. Proc R Soc Med 1976; 69:305-06 References 22 Saric M, Kulcar Z. Zorica M, Celie L Malignant tumors ri tire liver and lungs in an area with a PVC industry' 1 Berk PD (mod). Vinyl chloride-associated liver disease.. Environ Health l'erspect 1976; 17:189-92 Ann Intern Med 1976; 84:717-31 23 Mason TJ. Cancer mortality in U.S. counties with pint** 2 Zenz C. Occupational medicine principles and practices and related industries. Environ Health Ferspect 1975. application. OikaRii: Year Hook Medical Ptililislv-rx; 11:798-1 1975:789 24 Amaud A, Pommier D-S, Carbe L, Payan H, Chirpin J. I 3 Cordasco EM, Demeter S. Pulmonic manifestations of polyvinyl chloride exposures. Presented at Symposium, Polyvinyl chloride pneumoconiosis. Thorax 1978; 33:19 . 25 j Republic Hospital, Dusambc, Tajiskistan, USSR, October 1978 25 Darke CS (discussant) in Barnes AW. Vinyl chloride ltd the production of PVC. Proc R Soc Med 1976; 692^' I 4 McCoombs RP. Disease due to immunologic reactions In die hmgs. N Engl J Med 1972; 288:1186-91; 1245-52 281 26 Szende B. Lapis K. Ncmes A, Pinter A. Poeumoeoniorii I 5 Heath C, Falk JI. Creech J. Characteristics of cases of caused by the inhalation of polyvinyl chloride dust Md angiosarcoma of the liver among vinyl chloride workers in Lav 1970; 61:433-36 die United States. Ann NY Acad Sci 1975; 246:231-36 27 Lange CE. Juhe S, Stein C, Veltman C. Further results h 6 Kramer CC, Mutchler JE. The correlation of clinical and polyvinyl chloride production workers. Ann NY Acad Sci environmental measurements for workers exposed to vinyl 1975; 246:18-21 chloride. Am Ind Hyg Assoc ] 1972; 33:1930 28 Prodan L, Sochi J, Pislaru V. Ilea E, Pascu L. Experi 7 Sokol WN, Aelony Y, Beall CN. Meat-wrapper's asthma: a mental chronic poisoning with vinyl chloride (moo new syndrome? JAMA 1974;222:639-41 chlorothene). Ann NY Acad Sci 1975; 246:15963 8 Ward AM, Udnoon S. Watkins J, Walker AE, Darke CS. 29 Fulmer JD. Clinical aspects of idiopathic pulmonary fi Immunological mechanisms in the patliugcncxis of vinyl brosis, in Crystal RC (moderator). Idiopathic pulmonary chloride disease. Br Med J 1976; 1:936-38 fibrosis. Ann Intern Med 1976; 85:77973 9 Miller A, Teirstcin A, Chuang M, Sclikoff S, Warshaw R. Changes in pulmonary function in workers exposed to 30 Turner-Warwick M, Hoslam P. Antibodies in w* chronic fibrosing lung disease: L Non-organ-specific anti vinyl chloride and polyvinyl chloride. Ann NY Acad Sci bodies. Clin Allergy 1971; 1:83-95 1975; 246:42-52 10 SelikofF S, discussant in Ramcs AW. Vinyl chloride ami the production of PVC. Proc R Soc Med 1976; 69:277- 81 11 Camble J, Liu S, McMichael AJ, Waxweiler RJ. Effect of occupational and nonoccnpationa! factors on the respira tory system of vinyl chloride and Other workers. J Occup Med 1976; 18:659-70 12 Cordasco EM, Demeter S, Lira R, Wagner W. Occupa tional asthma updated. J Occup Health Safety 1980; 49:42-45 . 13 Lee CC, Bhandari JC, Winston JM, et al. Carcinogenicity of vinyl chloride and vinylidene chloride. J Toxicol En viron Health 1978; 4.-15-30 14 Viola PL, Bigotti A, Caputo A. Oncogenic response of rat skin, lungs, and bones to vinyl chloride. Cancer Res 1971; 31:516-22 15 Maltoni C, Lefemine C. Carcinogenicity bioassays of vinyl chloride: current results. Ann NY Acad Sci 1975; 246:195-218 16 Tabershaw JR, Caffey WR. Mortality studies of workers in the manufacture of vinyl chloride and its polymers. J 31 Crystal RC. Biochemical concepts and overall perspective of Idiopathic pulmonary fibrosis, in Crystal RC. Idiopathic pulmonary fibrosis. Ann Intern Med 1970; 85:783-85 32 Veltman C, Lange C-E, Juhe S, Stein G, Bachncr V. i I 1 I Clinical manifestations and course of vinyl chloride dec ease. Ann NY Acad Sci 1975; 246:6-17 33 Lilts R, Anderson II, NidkjLsoii WJ, et al. Prevalence of disease among vinyl chloride and polyvinyl chloride workers. Ann NY Acad Sci 1975; 246:22-41 34 Creech JN. Industrial screening; in Berk PD (modeta* | tor). Vinyl chloride-associated liver disease. Ann Intern I Med 1976; 84:720-22 | 35 Marsteller HJ, Lelbach WK, Mueller, R, Gedigk P. Un usual splenomegalic liver disease as evidenced by peri- ( tonoscopy and guided liver biopsy among polyvinyl chlor ide production workers. Ann NY Acad Sci 1975; , 246:95-134 36 Wagoner JK, Infante PF, Saraoci R. Vinyl chloride *d mortality? Lancet 1976; 1:194-95 37 Infante PF, Wagoner J, Waxweiler R. Carcinogen^ mutagenic and teratogenic risks associated with ' chloride. Mutat Res 1976; 41:131-42 Occup Med 1974; 16:50918 38 Purchase 1FH, Richardson CR, Anderson D. Chros>o- 17 Waxweiler RJ, Stringer W, Wagoner JK, et si. Neoplastic risk among workers exposed to vinyl chloride. Ann NY somal and dominant lethal effects of vinyl chlorideLancet 1975;2:410-11 Acad Sci 1976; 271:40-48 39 Funes-Craviuto F, Lambert B, Lindsten J, et aL Chromo 18 Monson RR, Peters JM, Johnson MN. Proportional mortal some aberrations in workers exposed to vinyl cWorafc- ity among vinyl chloride workers. laiHri 107-1; 2:397- IjiKet 1975; 1:45! 98 40 Infante PF, Wagoner JK. McMichael AJ, Waxweiler Bl. f 19 Byron D, Engholm C. Englund A, Westerholm P. Mortal Falk H. Genetic risks of vinyl chloride. Lancet 19 "- * ity and cancer morbidity in a group of Swedish VO.M and 1:791-35 t BFG39753 ~ ~ 2 7 \(W f& W 834 CORDASCO ET AL CHEST, 78: 6. DECEMBER. 1930 SAM Ilf TO THe eDITOR Communications for this section will be published as space and priorities permit. The comments should not exceed 350 words in length, with a maximum of fine references; one figure or table can be printed. Exceptions may occur under particular circumstances. Contributions may include com ments on articles published in this periodical, or they may be reports of unique educational character. Specific permission to publish should be cited in a covering letter or appended as a postscript. Pulmonary Manifestations of Vinyl and Polyvinyl Chloride To the Editor; I would like to comment on the paper of E. M. Cordasco, et al, entitled "Pulmonary Manifestations of Vinyl and Poly vinyl Chloride (interstitial lung disease): Newer Aspects," (Chest 1981; 78:898-34) and caution against any prema ture conclusions reached from this paper. While their article supplies interesting information, it does not substantiate their main contention that the three cases represent what they call vinyl chloride/polyvinyl chloride lung disease. Instead, each case is completely different and not really comparable. The first case represents an alleged pulmonary disease from the inhalation of pyrolysis products of PVC meatwrap ping film. The second case is an apparent exposure to vinyl chloride fumes; the third case represents one where the ex posure is polyvinyl chloride resin dust Each of these materials has different properties and characteristics and should not be considered a specific entity. Furthermore, the environmental information concerning exposure in each case is extremely scanty and limited. Therefore, having three individual cases of completely different exposures, and hav ing little information on the specifics of the exposures does not constitute a designation of a disease entity. This fact should be made clear! The first patient described was a meat wrapper exposed to PV'C film thermal decomposition products as well as emissions from the adhesive heat label. The exact details of the latter exposure were not given. Blood tests for phthalic anhydride were said to be elevated. Phthalic anhydride was said to be a decomposition product of PVC. This, unfor tunately, is not the case. The thermal decomposition of plain PVC has been studied extensively and emission products have been identified.1'* PVC alone is different from PVC meat packaging film, which also contains a number of selected additives including plasticizers (di-2-ethlhexy! adi pate) which can comprise up to 30 percent of film. Major emissions from hot-wire cutting of PVC meat packaging film are hydrogen chloride and plasticizer breakdown prod ucts including di-2-ethylhexyl adipate. PVC is not part of the emissions, nor is VC. Since phthalic anhydride and phthalates are generally not part of the PVC meat wrapping film, the elevated blood phthalic anhydride level is not due . to decomposition of PVC meat wrapping film. Materials " such as DEHP, MEHP, phthalic acid and phthalic an hydride measured in tissue or blood cannot be presumed to be the result of exposure to pyrolysis products of plasti cized PVC, nor from the metabolism of phthalate plasticizers. > Phthalic plasticizers and phthalic anhydride are present in \ a number of commercial products. Unless one has informa- i tion on ware normal blood and tissue level* measurement in the blood cannot be given any ^,1 ^ nificance. The information concerning normal bl^ of the phthalate compounds is not given in the m* Phthalic anhydride is a component of many plastic and also a constituent of the thermal-activated D 2.., ^ "hot-melt" adhesives.7 Thermal activation of the D ^ is performe:d by heating the labels from the _pr.: . **1, with possible emissions being phthalic anhydride. Ou ^ ^ has studied populations exposed to this chemical and*',>* not identified cases of interstitial lung disease, but noted cases of bronchial asthma.* Furthermore, a numkZ*'T recent studies of meat wrappers have not demonstrated ^ nificant lung disease.*-1* I seriously doubt, therefore ** the interstitial lung disease described only in one case *** due to exposure to PVC meat wrapping film emission*. *** V. The second case of the individual exposed to VC mp.ray 51 paint is perplexing. There is discussion on contents of ^ spray paint, indicating that vinyl chloride is one 0f 1 main components and not just a propellant. My informal 3? indicates that vinyl chloride is not used in this type of >*~ and therefore I question the accuracy of the information ' provided by Dr. Cordasco. Unfortunately, few environmental data are given and there are no details on other environme*. tal exposures. VC is a potent carcinogen and for the pa* - several years has been excluded as a propellant for cq^. v: mercial products.11 "I The third case is also confusing. This case involves a 5$. year-old man exposed to PVC dust during a reactor cleaning operation. Apparently, the exposure was transient, over a 5-6 week period. The only information we have concerning environmental air concentrations is the statement that PVC in the immediate operational area varied between 200-300 parts per million. This level is not possible. Dust measure ments are made in particles per cubic feet of air or weight fie mg or #*g) per cubic meter of air. Cases are measured in parts per million. Prolonged exposure to PVC has been reported to cause a pneumoconiosis, as indicated by Dr. Lilis in her commentary. Prolonged exposure is necessary and a 5-6 week exposure is unlikely to result in significant luijg disease. 'In summary, therefore, I would again caution against reaching any definite conclusions from the findings in this paper. The environmental data are scanty and inconsistent and in many cases erroneous. Actual levels are lacking and all environmental contaminants have not been adequately identified. The authors have, unfortunately, fallen into the common trap befalling many practicing physicians of at tributing an occupational disease to be present because a potentially toxic material is present in the work place, and without properly and accurately determining what the actual exposures are, in what concentrations, the duration of ex posure, as well as properly excluding other agents and non- occupational causes for the disease. Stuart M. Brooks, M.D., F.C.C.P, Head, Clinical Studies Division and O't Professor of Medicine and Environmental Health, University of Cincinnati Medical Center, Cincinnati References Vandevort R, Brooks SM. Polyvinyl chloride film thermal <5* decomposition products as an occupational illness. I Occupational Med 1977; 19:188-91 2 Encyclopedia of Polymer Science and Technology: Pi*5* tics, Resins, Rubber, Fibers, Vol 12 and 14. New lork: Interscience Publishers, 1968 262 COMMUNICATIONS TO THE E0IT0R BFG39754 CHEST, 81: 2, FEBRUARY, 1982 [ r-ir i -J-nrcW SL. Thermal degradation of organic polymers. ^*'ork- Interscience Publishers, 1974 l*4/* c Quenia M. Degradation of poly ( vinyl chlor- I Kinetics of thermal and radiation-induced de!j-*-hIorination reactions at low temperatures. J AppI Sci 1970; 14:1737 LTltJ VA, Piere LE. Thermal degradation of poly i chloride). 1. Structural effects in die initiation - ^^composition chain lengths. J Polymer Sci 1970; ..' 5^tner EC, Ball C, Weiss B. Analysis of the volatile 6 iZjjbu-ttion products of vinyl plastics. J AppI Polymer Sl979; 13:377 i v. w 5M, Vandevort R. Polyvinyl chloride film thermal r-7 sition products as an occupational illness. J '?&. JwupTtional Med 1977; 19:192-96 CA, Bernstein IL, Emmett EA, Brooks SM. In * '_tKO demonstraton of specific IgE in phthalic anhydride r^rsensitivity- Am Rev Respir Dis 1976; 113:701 'I RN. Respiratory health and polyvinyl chloride Lmes. JAMA 1977; 237. 1826 ~T fauttipe PE. Finley TN, Martinez N. The search for l^atoty obstruction in meat wrappers studied on the ^ Am Rev Respir Dis 1979; 119:611 t Gtfnbie J et ai Effects of occupational and nonoccupa** lunal factors on the respiratory system of vinyl chloride ~Sr-. and Other workers. J Occupational Med 1976; 18:659-70 ^ X, ike Editor: J }i3\-e a follow-up report from Dr. Kerkay, Professor Biochemistry at Cleveland State University, who has working with his group in conjunction with our clinical r -- 0n polyvinyl chloride. He was co-audior of the paper ^ceotly published in Chest. His. comments follow: *Dr. Stuart M. Brooks* criticism of the first patient's re- jth* and biochemical data is out of context When he refers ! published data (his references 2-6) of PVC breakdown products, he cites the thermal decomposition of bulk PVC athn than the plasticized final product His reference 6 I our findings qualitatively (p 383 and 390) where &rr report the boiling off of phthalate plasticizers during &cmial decomposition of certain (plastic E & G) PVC f compounds. In his reference I, Dr. Brooks cites an article by Vrodevort and co-workers, which was published in 1977 * and deals with the thermal decomposition of meat packaging Bim There have been changes and improvements in the plasticization of meat wrapping films during the past 4 I*J wars. Our laboratory does have CC and HPLC tracings of Ac patient's blood and urine indicating die presence of phthalate and not adipate plasticizers, as confirmed by mass spectroscopy. It is true that many commercial products con ns phthalate plasticizers; however, these plasticizers are ltded out of plastics only if the plastic comes in direct contact with blood (or lipid containing solutions) or when labeled following volatilization.- We have tested blood and rine specimens from over 100 normal individuals and not oar of them showed the presence of phthalate or adipate plasticizers in greater amounts than the detection limit of w method of 40 ng/ml serum or urine.* Therefore, we as- *nt that the normal phthalate level is less than 40 ng/ml, which is undetectable. "Our Bindings of DEHP, MEHP, phthalic acid, and phthalic anhydride in this patient resulted from the exposure to *bmnal degradation products of the plasticized PVC and fnxn the metabolism of these phthalate plasticizers. "The cytologic examination of lung tissues from the three ***** presented in our paper are very similar to the changes bserved in lung tissues of dogs following intravenous in- ( jection of chemically pure bis (2-ethyIhexyl) phthalate (DEHP)."4 Now in conjunction with the special vinyl chloride paint composition that one patient had been exposed to, this has been very difficult to follow-up because the dental equip ment company, known as Weber of Canton, Ohio, has totally closed down, and I am in the process and have al most completed the process of finding additional information through the major dental equipment company in New Jersey. They have referred me to the dental school here and also through Dr. Carl Zenz of Milwaukee, Wisconsin.* A special paint which is identical to the chemical B, is now being analyzed for total and specific contents. The third case delineated the PVC occupational atmos pheric level at 200-300 parts per million, which is what we had obtained from the industrial safety director of a specific plant* Our chemist co-author discussed this in detail with die Research Chemist Supervisor of B.F. Goodrich Company of Akron, Ohio (new plasticizer division), who stated that this pollutant can be reported in micrograms per cubic meter or in parts per million. We are fully aware of die fact that as a particulate, this is appropriately reported in micrograms or milligrams per cubic feet of air. Therefore, we were in error as die occupational atmospheric reading should have been reported as micrograms per cubic feet. We have seen many patients, in consultation with two chemical plants in New York State, with vinyl chloride and potyvinyi chloride exposures.* We believe that die patient reported represented a case of subacute interstitial pneumo nitis and not de-facto pneumoconiosis. If one reads die article carefully, on page 833, paragraph 2, we alluded to die fact that the relationship is highly presumptive and not conclusive as to cause-effect relation ship in the development of interstitial fibrosing pneumonitis. We cautioned in our conclusions that the total clinical sig nificance of the factors referable to die biochemical changes were still unknown and will be pursued further. Consequently, we have felt that the published paper has left some unknown answers and in no way have implicated these agents to be direct causative factors of pneumo conioses in any of these three patients. We do feel that these histopathologic changes are probably related to the excessive exposures of die VC/PVC group of agents. There fore, we disagree with Dr. Brooks that die authors have "fallen into the common trap of attributing occupational disease to be present because of potential toxic material in the work place." Edward M. Cordasco, M.D, F.C.C.P., Director, Department of Respiratory Therapy, Pulmonary Medicine, Cleveland Clinic, Cleveland References 1 Draviam EJ, Kerkay J, Pearson KH. Separation and quantitation of urinary phthalates by HPLC. Anal Lett 1980; 13:1137 2 Michel A, Bert M, Sainrat A, Cuyot A. Role of PVC and di-2-etbyl hexyl phthalate in the smoke formation from p'asticized PVC. 3rd International PVC Convention, 1979; 365-68 3 Lewis LM, Flechtner TW, Kerkay J, Pearson KH, Nakamoto S. Bis(2-ethylhexyl) phthalate concentrations in the serum of hemodialysis patients. Clin Chem 1978; 24:741 4 Chem WS. Bis(2-ethylhexyl) phthalate levels in dogs, and in uremic and nnn-uremic patients. Ph.D. Disserta tion, Cleveland State University, 1979 OffST, 81: 2, FEBRUARY. 1982 BFG39755 COMMUNICATIONS TO THE E01T0R 263 cn Cr * O O <