Document 06k321ZKEm5m1Q4kV3n4Bk33b

C- AtLLEA ^CAOHC N* HCCMMAN CHAC< M. MEEHAN WILLIAM H. *OHt*ANI, *> MALCOLM D. MACAATMUft MTDl V. ALACK MAATIN W. ACACOVlC JOHN A. CLOAEO CAAOLC C- HAAAl* MICHAcl r. moaaomC maaa ro* cvcma VOKH OVftCCM ACTKA L- k* CAtJZ CHPMSTIMC A. MtAOHtA ftHIdUY A. fUiflHOTO LAWACMCE A. MALAAIM AALAM A. IIMMONfl AETCA A, IUUC* COWAAQ U AOAWEA TCNAtMCC Q. UOMCA WARY MAIVTNA MCNAMAAA VOMM . AICNAAM* fr OOUALAA JAAACTT SMCILA A. MICLAA AL*CLL M. WOH JAM M. WAMATEO ILEMC AfHACL HCLLEA *U*AM T. CONTI IUIAM J. ALUM AATAIC* J. HVRDM A. CPtA'O TAUTrCJT OAVID H. JETT MAUACCN A. O'CONNELL kaacn c. coelacao* NINA M. CIMSTIIM*** AtAN O. MOMMNH MAAKA. IIKVIRtH1 AOMITTCO IN AEMMAYVVANIA ONLY ADMITTED IN VIAOINIA ONLY MAOMJTTCfi IN MARYIAMO ONLY LAW OFFICES Keller and Heckman 1150 X7rm STREET, N.W. SUITE lOOO WASHINGTON, D.C. 80036 (20 2) 030-5000 July 8, 1987 : *.T n*./'< eiCHTirtc trr 0AN1CL S. DIXLCII dumumo r. oeootH CHAftLCS V. NCOC* TCbO TCLCCdVICM icoai CALC AOORCSt "KCkMAMWNITCM'S OIMCT CMAt * vr Ms. Meredith N. Scheck The Vinyl Institute Wayne Interchange Plaza #2 155 Route 46 West Wayne, New Jersey 07470 Re: Final comments on EPA RCRA Toxicity Characteristic Revisions Dear Meredith: Enclosed is a copy of the comments we filed with the Environmental Protection Agency (EPA) on July 2, 1987 in response to the agency's supplemental proposed rule making revising the toxicity characteristic under the Resource Con servation and Recovery Act (RCRA). We received a number of helpful comments in response to the draft we circulated on June 22, 1987. The revisions emphasize the impact that the EPA proposal would have without realizing any environmental benefits. Because some polyvinyl chloride (PVC) waste is co-disposed with municipal solid waste, we revised the comments to indicate that industrial waste is not typically co-disposed with municipal waste in landfills. In adKfcion, our comments relating to the sampling of a sludge were jplAted due to a variety of differing viewpoints on this subject within the Institute. Finally, a recommendation that EPA adopt a small quantity trigger was added so that small amounts of wastes would be exempt. A small quantity exemption would be particularly helpful for spills or other incidental discharges. EPA has recently extended the comment period until August 16, 1987. 52 Fed Reg. 2418.1 (June 29, 1987). Thus, there is an opportunity to file supplemental comments on behalf Ms. Meredith N. Scheck July 8, 1987 Page 2 Keller and Heckman of the Institute. Naturally, individual companies can also file individual comments. If you have any comments or questions or if I can be of any further assistance, please let me know. Cordially yours, Peter L. de la Cruz cc: Robert D. Luss, Esq. W. C. Holbrook Joseph C. Ledvina Charles E. O'Connell Lewis R. Freeman, Jr. Robert W. Sherman Hugh Patrick Toner Enclosure It Sluclus |4. I. 25. It sly 0 1 1 3 0 i b 1 12 E OB 0.6 30 1.2 0.6 07 09 6.1 b 0.2 1 07 i 07 b 04 0 07 9 4.5 30 21.1 tout discovered cause. 14.25, 46). (O * observed Italy 0E 0. .* 19 T 0.5 27.4 5.0 4 52 3 2.7 t 2 70 1 0.9 ) 4 77 3 36 56.4 7 66 77.5 Tabic 3. Mo'i.iiiiy itoin cancel ol the liver end other causes among vinyl chloride worker* >n 49 nMms in me lour principal studies combined (4. 14. 25. 46) (0 = observed number of deaths. E = expected number ol dealhs. SMB * standardized mortality ratio) Cause ol death 0E Cancer ol the liver* Cancer ol other sites Other diseases Accidents, poisonings, and violence Ail causes 59 609 t 547 226 2 441 8 45 . 599.35 1 644.89 295.15 T4T B4 Including cancers ol the gallbladder In the aeries Irom the United Slates. -SMR 696 t02 64 77 e 14, Mortality Irom various cancers among vinyl chloride workers In 40 plants In (he lour principal studies combined. iSbaerved number ol deaths. E exposed number ol dealhs. SMR a standardized mortality redo) wsrr----------------------------------------------------mgs er cues o< cancer 'iMi end pharynx Mbn system {other than Itver) MSsbtleiy system tfcwwi'yiliiery system Mmmoir* ..(emphatic and hematopoietic system OE 16 16.57 125 154 59 223 229.36 211 214.09 70 6261 2 1 94 29 1954 2 0-43 57 50 87 63 63 24 Source of Information* iif 1. 2. 3. 4 ii 1. 2. 3. 4 97 1. 2. 3. 4 99 1. 2. 4 m 1. 2. 3. 4 2. 4 148 1. 2. 3 2 112 1. 2. 3. 4 131 t, 2. 3. 4 *JUSetfte< then ol the liver 609 599-35 102 t, 2. 3. 4 ^*1 a United Slates study {14). 2 a United Kingdom study {25). 3 = Canadian study (46). and 4 a Italian study (4), k*'l * $>, 3jtijL, Tease V Mortality from various cancers among vinyl chloride workers: Supplementary evidence (4, 7, 22, 49). (O * observed l deaths. E s expected number ol deaths. SMR = standardized morteiiiy ratio) `*'-f tyee or clast of cancer .bpeeinre syslem - jwi tuning the liver) tw Mstanmns *** 1r4 irtteaphaitc and hemato,mut system !OBr Maciudmg the liver) wdudmg me liver Federal Republic of Germany (11 plants) bE 35.0 31 6 23.5 24.6 2.1 1.3 16.5 7.7 107 24.3 87.6 B9.7 Norway (1 plani) OE 3" 1.44* 5 2.84 4 0.79 2 0.16 Sweden {1 plant) OE 3 1.78 2 0.33 6 14.33 22 20.16 5* 2.11* Italy |l plant) OE 1 1.2 0 15 0 0.1 0 0.7 4 2.0 5 57 Four countries combined (14 plants) O E SMR 39.0 31.5 4.0 4.1 2.0 16.5 22.7 119.6 34 44 3072 0.69 1.63 0.16 6.4 41 43 117.67 113 103 196 55 102 : and cases In the Norwegian study, r pi the Intestine only, r ot llte lung and brain only, for a total of four), but bed as an angiosarcoma evidence that the excess mortality from liver MT (or liver and gallbladder cancer in the US series) be attributed principally if not wholly tp the known III lord of angiosarcoma is obtained in a comparison aceu deaths with the numbers of deaths from Mpoaaramus recorded in the Register of Liver Angio sarcoma Cases (maintained on behalf of the Associa tion of Plastics Manufacturers in Europe by the Im perial Chemical Industry PLC) before the end of the follow-up period (Bennett, unpublished). Fifty-one ex cess liver cancers are recorded in the combined data, and 49 angiosarcoma are recorded in the Register for 69 Table . Mortality Item lung cancer In the series from ihs United Stataa (US) (14) and ma Unilad Kingdom (UK) (25) by characteristic* relevant lo an occupational hazard. (Osobserved number of daatna, E * expected numoer ol deaths, SMR a standardized mortality ratio) be seen than in other groups. This circumstance is illustrated by table 6, which shows that (he SMR values are slightly higher for men observed 20 yearsotjnore after first exposure than for men observedfor Data enaracttrtstic1 4 Category 1 O* E SMR Category 2 o* E SMR men employed before I9S6 in the UK dtan)HMnen first employed after 1955 (when exposufelwB) are believed to have been lower), for men emptofSa for Observed 20 years or more after first employment (1), others (2) Employed 10 years or more in me US (), others in me us (2) Employed before 1956 in me UK (1). others in the UK (2) Ever employed ss autoclave worker In the UK (1). others in me UK (2) 114 113.06 100 55 52.45 105 52 St.39 101 16 17-06 94 55 93.53 91 63 53.44 99 29 40 50 72 65 74.52 87 longer than for shorter periods in the US, and for autoclave workers in the UK (among whom the angio sarcoma cases have mostly occurred) than for other workers. The differences are all small or very small. They are, however, all in the same direction, and the probability that the rates should all be higher in the groups in which an occupational hazard is more like ly to be seen in each of the four pairs of groups is I in 16. Additional information from other sources is given in table 5. A total of 30 deaths (or cases) was observed, and this figure increases to 31.5 when allowance is Tba numoara in parentheses dasignaia the category. * Saa lootnoia to taoia i lor obaarvad daatna in th US. made for the number of deaths due to unidentified causes in the German study (SMR becoming 103). In the German study the SMR was higher for the men (he relevant periods for the three countries and the two who had been exposed for 10 years or more than for Italian plants1 that are covered by the survey. those who had been exposed for shorter periods (III . Hone of the 120 cases yet recorded in the Register against 79), and, in the Norwegian study, four of (he Were in men who were first exposed after 1969. and five cases observed occurred in men whose occupations ne of the 43 men affected in North America were were regarded as involving high exposure against 1.82 tit exposed after 1964. All may. therefore, have been of the 2.84 expected. Both the German and the Swed exposed to concentrations of several hundred parts per ish studies derived the expected numbers of deaths million, and many may have been exposed to concen from national mortality rates for a single year towards trations appreciably higher (unpublished report by Ban- the end of the study period. The expected numbers of to Air Products and Chemicals Inc in 1981). deaths are likely, therefore, to have been overestimated and the SMR values correspondingly underestimated Lung cancer. The idea (hat exposure to vinyl chloride might cause cancer of the lung was suggested by Mon- as the mortality from lung cancer had been rising throughout the period of observation. son et al in 1974 (36), when (hey noted 13 cases against an expected number of 7.9 in a study of proportional mortality. The combined data shown in table 4 do not provide any support for the hypothesis, either for res piratory cancer as a whole (SMR 97) or for the speci fied data for lung cancer in the US. the UK, and Italy (SMR 99). There are, however, consistently higher risks in the subgroups of men in the US and UK series, in which occupational hazards would be more likely to 1 Twenty-nine were registered as occurring in the United States against an excess of 33; only 20. however, were iden tifiable in both series. Inquiry has, as yet, failed to reveal information about the histology of the remaining 13 in the cohort study and the origin of the nine extra deaths in the register. Nine deaths were registered as occurring in the United Kingdom gainst an excess of nine, but one of the registered cases was certified as due to a benign hemangioma and not related to the liver (code 227 in the eighth revision of the International Classification of Diseases). Ten cases were registered as occurring in Canada against an excess of eight; two were recorded as being in men who had been employed for five years, and it is possible that (he actual duration had been slightly levs than five years with con sequent exclusion from the Canadian cohort. One case was reyistcred as occutnng in one ot the two Italian plants t*H-tiiu ait excess ( less than one. Brain cancer. The idea that vinyl chloride might cause brain cancer was also suggested by Monson et al (36) when they reported five cases against 1.2 expected. The combined data that are shown in (able 4 provide some support for this hypothesis. The cases of Monson et al (36) were, however, observed in US workers and must be presumed to be included in the total reported by Environmental Health Associates (14); therefore they will have contributed a substantial proportion of the total in table 4. As a test of the hypothesis the data of Monson et al ought, therefore, to be subtracted from those in the table. Their investigation.was not a cohort study, and their expected deaths do not cor respond exactly to (hose in table 4. If, however, the observed and the expected cases are both subtracted from the totals, twenty-four observed deaths remain against approximately 18.3 expected, a difference which might easily occur by chance (P one-tailed = 0.1).^ 4 If the study of Waxweiler et a! (50) is regarded as the origin of the hypothesis. 2b tleaihs .ire let I ;iir.uni IS *)J cspcctcJ (P one-tailed - 0.07). Addition, given in tat little furthet one of the t occurred in. less than a > the excess di German stu chemical wo deaths after causes again; PVC fabrica for deaths fr< *.oncers oj t} idea that vin> U phatic and hr the lymphatic AGaffey (-J5) studies, wher from lymphot against 2.5J e* the lymphatic petted. These if the laborato suggesting that tally in anima1. imn (29). The cause lymphor ous constderat studies that arc support for the lymphatic and h< grther (37 death and very little mi fiir cancers of the fey's definition 300-203 and 2< i-1 (35 deaths age 'Moreover, hard GalTey's initial r 1.36 expected, ,,,, Little additio 'fenlu of the Gs ty obtained ; (based on IS obs titfkmance is mac [fcaown causes) a nexposed grt PVC fabricau 'exposed workers keen exposed for was most ma for five years or n the number of di a M r - pected. 5M <<'./ \[ >.' ICC is .lues more r, for r men Is are rd for id for angioother small, nd ihe in the e likeps is l % given served, ince is miHed 03). In ie men ian for ds (i 11 r of the paiions nst l -82 e Swed' deaths towards nlxrs of mated ,mated -n rising ;ht cause el glOW $ ;ted- The ide some onson ci kers and reported therefore onion o! s die data ubtractcd i was iioi 3 not cor* vever. the ubiraclcd h$ remain difference ,entailed = ` asilie origin ,94 expected Additional inforinaiiou Irom two other sources is given in table 5. The small excess reported provides little further evidence of an occupational hazard, as one of the two deaths observed in the Swedish study occurred in a young man who had been employed for less than a year when the diagnosis was made, while the excess death rate for brain cancer observed in the German study was less than dial observed among chemical workers not exposed to vinyl chloride (2.9 deaths after allowance for deaths from unknown causes against l .6 expected) and among workers in the PVC fabrication industry (5.9 deaths after allowance for deaths front unknown causes against I. i expected). Cancers oflymphatic and hematopoietic tissues. The idea that vinyl chloride might cause cancer of the lym phatic and hematopoietic tissues -- more specifically the lymphatic tissue -- was suggested by Tabershaw AGaffey (45) and by Waxweilcr et al (50) in two cohort studies, when they found, respectively, five deaths from lymphomas in the most heavily exposed workers against 2.54 expected and four deaths from cancers of the lymphatic and hematopoietic tissues against 2.5 ex pected. These small excesses might have been ignored if the laboratory findings had not been interpreted as suggesting that lymphomas were produced experimen tally in animats exposed to vinyl chloride by inhala tion (29). The idea that similar exposure might also cause lymphomas in humans, therefore, merits seri ous consideration. The data from the four principal studies that are summarized in table 4 provide little support lor the hypothesis when all cancers of Ihe lymphatic and hematopoietic tissues are considered to gether (57 deaths against 50.87 expected, SMK 112) and very little more is obtained from the separate data for cancers of the lymphatic system {Tabershaw & Gaffey's definition of Id) list numbers, eighth revision, 200--203 and 205 being used) (hat are shown in table I (35 deaths against 29.40 expected). The position is, moreover, hardly altered iT the data in Tabershaw & Gaffey's initial report arc subtracted (29 deaths against 23.36 expected. SMR 124). Little additional information is provided by (he results of the German study (49). (See table 5.) This study obtained an SMK of 214 for exposed workers (based on 15 observed deaths, increased to 16.5 when allowance is made for the number of deaths from un known causes) against SMR values of 77 and 34 for an unexposed group of chemical workers and a group of PVC fabricators. It showed that the excess of the exposed workers was present only for men who had been exposed for more than one year and that this ex cess was most marked for men who had been exposed (or five ytats or more (10.7 deaths after allowance for the number of deaths from unknown causes against 4.0 expected, SMR 268, Pone-tailed <0.0l). Melanoma. An excess of melanoma was reported for Norwegian workers by Hcldaas et al (22). who raised the possibility that vinyl chloride might have produced the disease. Tour cases were observed when 0.79 were expected, and three of (he four were in men whose oc cupations involved the highest exposures (against 0.51 expected). At the time of the writing of their report, one further case had been detected with onset three years after the closure of the study. Subsequent studies in other countries have, so far. reported only two deaths against 2.0 expected. (See tables 1 and 5.) Thyroid cancer. An excess of thyroid cancer was also reported in ihe Norwegian study (22), in which two cases were observed against 0. IfagKcted. The inves tigators were not aware of aayeqBpiludier indicating an excess of this type of caitofjjflfiiiey drew no con clusion from (heir observation, tjppf the three major studies (hat have been reported mice the Norwegian observation was made gave no data for thyroid can cer; the third reported two deaths against 0.43 ex pected. (See table I.) One death from thyroid cancer, it may be noted, was reported in the US by Monson et al (36). Cancers of the digestive tract. Suggestions that vinyl chloride might cause cancers of the digestive tract in general have sometimes been made, but they have not taken adequate account of the contribution of cancers of the liver to the total number of cancers of the digestive system, particularly when it is borne in mind that some liver cartcers are likely to be misdiagnosed as cancers of other organs. The combined data from the four principal studies shown in table 4 weigh heavily against the idea that any such effect has been produced. Other cancers. One of the remaining types, or classes, of cancer listed in table 4 shows a statistically signifi cant excess, namely, the heterogeneous group of "other cancers" (83 observed deaths against 65.24 ex pected. P two-sided <0.05). This excess is only mar ginally significant and may be a chance observation. The most likely explanation is. however, that a few angiosarcomas of the liver were not recognized and were diagnosed as secondary liver cancer or carci nomatosis. site unknown, the number of deaths in this category therefore being increased. Hazards of nonma/ignant disease No previous study has suggested that any nonmalignant cause of death other than cirrhosis of the liver would be likely to be increased as a result of exposure to vinyl chloride, and cirrhosis of the liver is presumed to be increased only because of the liver changes that were observed as part of the "vinyl chloride illness" (24. 31, 33). Two other possibilities have, however, been raised, namely, the production of nonmaiignant respiratory disease, because of the changes in lung function and radiographic appearances that have been Table 7. Mortalily *rom selecied nootnilignim causa* and all cauaaa m iht lour principal studlas combined. (O * observed number of daaiha. ^expected number of deaths, SMR iiindtrdind mortality ratio) Type ol disease 0 E SMR Source of information* Bronchitis. emphysema* 80 66.83 120 1, 2 Other respiratory disease 71 125.78 56 1. 2 recorded for men exposed to PVC dust (2, 26, 27, 44), and acute cardiac death, from analogy with the effect of other halogenated hydrocarbons servation of an increased mortality! infarction in the few years folkn exposure in the Swedish PVC j Relevant figures for the numbers of (Seat and other nonmalignant causes that are obtainable from the four principal studies were given in table 2. and they have been summarized in table 7. All respiratory disease Ischemic heart disease Other circulatory disease* All circulatory disease* Cirrhosis of th* liver Other disease 180 797 262 1 103 46 238 200.82 665.73 264.55 1 209.35 66.26 36807 All nonmalignant disease AM external causes 1 547 1 844.50 226 295.15 80 1, 2. 3, 4 90 1.2 95 1.2 91 1, 2, 3. 4 69 1. 2. 4 6$ 1. 2. 3, 4 84 1. 2. 3, 4 77 1. 2. 3. 4 All nonmalignant cauaaa All ceuaea 1 773 2 139.65 85 1. 2. 3, 4 2 441 2 747.85 89 1. 2. 3. 4 1 Untied States study (14), 2 a United Kingdom study (25), 3 a Canadian study (46), and 4 * Italian study (4). * Bronchitis m the United Kingdom study, emphysema in the United States study. 1 Includes cerebrovascular disease in the United Kingdom and Italian studies. Table 1. Mortality from chronic obaifuciive lung disease* in lha series irom the United States (US) (14) and the United Kingoom (UK) (25) by cnaractanstics relevant to an occupational hazard. (O = observed number ol deaths, E = expected number pi deaths, SMR = standardized mortality ratio) Dal* characteristic* Category 1 0 E SMR Category 2 0 E SMR Observed 20 years or more alter first mpioymenl In ihe US (i), others In the US 12) Employed 10 years or mors In th* US (1). othars in tha US (2) Employed before 1956 In th* UK (1). other* In the UK (2) Ever employed as an autoclave worker in the UK(1), others in me UK (2s 30 16 20 3 15.6 190 10.9 147 30.17 86 6.S5 46 11 7.0 157 25 12.0 208 10 13.60 74 33 37.22 89 Described as emphysema in the US study and as bronchitis in the United Kingdom study. * The numbers in parentheses designate the category. c Men e-e> employed as stagger or drier, occupations which would have caused the greatest occupational exposure to poiyvmyi chloride dust, experienced one death Irom bron chitic against 4 98 expected. Cirrhosis of the liver. Three of the four principal studies gave separate figures for cirrhosis of the liver, none of which showed an increased mortality (table 2); in combination (hey gave an SMR of 69 based on 46 deaths. The fourth study, which did not give sepa rate data for cirrhosis of the liver, reported four deaths from all diseases of the digestive system combined against 3.85 expected and noted that the four included two that were certified as due to cirrhosis of the liver, but actually due to angiosarcoma (46). In the two sup plementary studies in which data were given for this disease, the SMR was 82 in one, based on 15.1 deaths after allowance for the number with unknown causes (49), and 133 in the other, based on seven deaths (37). Nonmalignant respiratory disease. The data for nonmalignant respiratory disease are confusing in that the total SMR from the combined data for the four prin cipal studies is 80 and is the sort of figure that is com monly found in healthy industrial populations, yet the US study recorded a substantially increased mortality from emphysema (41 deaths and an SMR of ISO be fore any allowance was made for deaths from un known causes). No such excess was found in the UK, where 36 deaths from bronchitis gave an SMR of 82. International comparisons of chronic nonmalignant respiratory disease are complicated by the usage of dif ferent terms to describe what it is now agreed is best called chronic obstructive lung (or pulmonary) disease, but which in the past tended to be called emphysema in the US and chronic bronchitis in the United King dom. It must, therefore, be presumed that the two categories of "emphysema" and "bronchitis" used re spectively in the two large national studies were meant to describe the same thing. One must assume, there fore, that the experiences in the two countries were very different, despite the fact that both related to coht that had very similar experiences of angiosarcoma of the liver and so, presumably, fairly similar exposures to vinyl chloride. Separate figures are shown in table 8, where avail able, for the mortality observed among men wiih dif ferent durations and intensities of exposure. Unlike the data for cancer of the lung that were shown in table 5, they provide no consistent evidence of a greater risk in the groups in which an occupational hazard would & be expectec vironmenta If give anj from empf hardly bed no overall e however, th & if. bydeficienc respiratory. Other respir the questioi could he a Health Asso that they we the out-o; the coding o "Other respir included emi & emphysema t be classified to 502, and if of the emphy bitomecateg number 527.1 for both thee frouly deficit respiratory di No excess n aad asthma" v :v.,, Mwith 6.3 d< umber of de CmJfavascuta, r'v' fderotic) heart dode the vast .Macule cardia .Wg national stv ) Increased m< > of diseas i recorded ii theSMR val "d (here is no i (the subsidiary In parn mortalii item in the s, SMR 61) workers (9 > slight incret Twts recorded ) study (49),) '.* The deaths ttlrib tvx and the coi i.i> wiion for i :. at Health A lor i I l.lk V ,!. ~Jk -.M2. 26. 27,44). ogy with the effect <$ (25) and the ob it (tom myocardial ng the cessation of :ssing industry (35). f deaths from these hat are obtainable :re given in table 2, in table 7. the Tour principal itfhosis of the liver, sed mortality (table >MR of 69 bated on ch did not give separeponed four deaths ve system combined hat the four included cirrhosis of the liver. (46). )n the two supa were given for this based on IS.I deaths with unknown causes on seven deaths (37). tse. The data for non'ttfusing in that the . .4 for the four prin* i of figure that is com* iai populations, yet the lly increased martaiity nd an SMR ofj*0 be* : for deaths friim un' was found in (fee UK. tis gave an SMR or 82. chronic nonmaiignant ated by (he usage of dif* n is now agreed is best (or pulmonary) disease, o be called emphysema litis in the United King* presumed that the two nd "bronchitis" used rer<, lonal studies were meant ' )ne must assume, there*; ie two countries were very it both related to cohorts nces of angiosarcoma of1 . fairly similar exposure* n in fable B, where avail ved among men with dif* tes of exposure. Unlike the: that were shown in table: t evidence of a greater risk', ccupational hazard would t9t npecied to be concentrated. The authors of the Enital Health Associates report (14) were unable i'll** any explanation for the increased mortality emphysema, and they point out that it could ' be due lo excess cigarette smoking, as there was l overall excess for cancer of the lung. It is striking, r, that the excess is more than compensated for tendencies in the other categories of nonmaiignant 'disease (pneumonia 15 deaths,' SMR 47.0; -respiratory disease 14 deaths. SMR 42.6), and rpntton arises whether the emphysema excess be a dassificatory artifact. Environmental I Associates (14) list all the 41 deaths which show they were coded under ICO number 527 which, |tea OUt-of-daie seventh revision that was used for rwdtat of ail deaths in the study, was the code for r respiratory disease not otherwise classified" and emphysema. Under that revision, however, i that was associated with bronchitis should lifted with bronchitis under ICO numbers 500 [fv MB, and the possibility may be considered that some I Ac emphysema deaths should have been classified 'Category of respiratory disease other than ICD 327. If this were the situation, it could account i the excess mortality from emphysema and the deficient mortality from other nonmaiignant lory diseases. j^lddCtttu mortality from "bronchitis, emphysema, r^Mmthma" was observed in the German study (SMR j>M wtaii 6.3 deaths observed after allowance for (he Of deaths from an unknown cause) (49). V00^0trumlardisease. Data for ischemic (or arterio|ddA**c) heart disease (which may be presumed to in- i She vast majority of all deaths certified as due : cardiac disease) were given only by the two JfcMtmil studies, and they provide no evidence of j[|R4ncrc4>fd mortality. The SMR values of 90 for this diseases and of 91 for all cardiovascular dis^inc recorded in the four principal studies are typical ;SMR values of healthy industrial populations, here no suggestion of any occupational hazard tmft*irliary analyses provided by the two national IT.lA particular, there is no evidence of an in- Lmortality within one month of leaving em* In the UK study either for all workers (52 !SUR6i) or for the most heavily exposed auto- (9 deaths. SMR 42). ; Increase in ischemic heart disease mortali recorded for the exposed workers in the Ger (49), but it was less than that recorded fori i attributed to different groups of respiratory disl the corresponding SMR values that are cited in m for (he US sludy are as given by the EnvironI Health Associates (|4) and have not been adjusted sM (or (he number of deaths from an unknown r. Intake account of these deaths, the observed deaths tJMN values can both be multiplied by 1.0674. (he unexposed chemical workers and the PVC fabri cators (SMR values of 127. 131, and 158 based on V7.2, 126.7, and 109.7 deaths, respectively, after allowance for the number of deaths from unknown causes). Discussion The information that has now been obtained about the long-term health of men occupationally exposed to vinyl chloride is massive and compares favorably with that available for any othoroccupational group. Two facts are outstanding. FsnfedAe men have experienced a specific hazard of a IJAdPbswKer that is normally extremely rare, iiiimfri aiyj^lhrcoma of the liver. The rarity of this disease dndinPker conditions made (he detection of the hazard easy; but the long latency period before the disease appears after first exposure (almost always more than 10 years and usually more than 15 years) meant that a large number of men had been exposed before the hazard was detected and that it will still be many years before the extent of the pro tection provided by the reduction in exposure in the 1960s and that of the further reduction that followed (he recognition of the hazard in 1974 are known. There is. unfortunately, no effective treatment for the dis ease. and the number of cases is reflected in the num ber of deaths. Some 50 deaths have occurred among the 16 740 men who were followed in the four prin cipal studies that have been reviewed in this report, so that approximately I in 335 men have been affected, 2 V* of the deaths having been due to this one cause. Eventually many more men must be expected to de velop the disease. One estimate (38) suggests that the total may be increased 10 times, but a more realistic estimate is two to three times (19). The second outstanding observation is that the mor tality of the exposed men, other than that due to angiosarcoma of the liver, is typical of the normally healthy industrial worker -- that is not to say that no other hazard exists, but that the effect of any other hazard is small. The massive data that are now available provide no reason for thinking that any hazard other than one of cancer has been overlooked. It is, however, still dif ficult to decide whether vinyl chloride produces a risk of developing cancer other than angiosarcoma of the liver which might be small compared to the risks produced by nonoccupacional causes, but yet abso lutely almost as large as the risk of developing the nor mally very rare angiosarcoma. One of (he many hazards suggested can be dismissed, as there is no evidence to support it. namely, that of vinyl chloride as a cause of any cancer of the diges tive tract other than angiosarcoma of the liver. Two hazards (of melanoma and cancer of the thyroid) have been suggested only very recently, and few of the avail able studies have provided information about them. There is no good theoretical reason or laboratory evi dence to suggest that either should be produced by 73 yEM-239243 vinyl chloride, and, in tight of present evidence, the simplest explanation is that the reported excesses are the chance effects that must be expected when many different types of cancer are studied in several different populations. So far as melanoma is concerned, it has to be remembered that the diseaae has become much more common in recent years in Scandinavia (where the excess was reported) due, it is believed, to the popularity of sunbathing and the increased oppor tunities for Scandinavians to travel to the warmer pans of Southern Europe and North Africa. The extent to which this change may have affected the observation in Norway needs to be examined. Two other hazards (of lymphoma and brain cancer) were suggested by the early results of some of the US studies. That vinyl chloride might produce a hazard of lymphoma was initially supported by the prelimi nary results of animal studies, but the complete results of the many investigations that have been undertaken (see reference 29) do not suggest that lymphoma or any other cancer of the hematopoietic system is liable to be produced. There is, however, some evidence that brain tumors can be produced in rats (29). The hypoth eses that lymphomas and brain cancers might be produced by vinyl chloride have been supported by the observation that both these types of cancer have caused death more often than might be expected from national mortality rates, but the excesses observed in the com: bined data from the four principal studies in this re view are small and not statistically significant, and the hypotheses remain unproved. The small excess of brain cancer is particularly difficult to evaluate, as mortal ity rates from this disease have changed rapidly over time as methods of diagnosis have improved and the suspicion of an occupational hazard (which was raised in 1975) could have influenced the findings. What ex cess has occurred has been limited to the US and Ger many, and the German findings carry little weight, as the excess was found in each of the three occupational groups studied, irrespective of the chemicals to which they were exposed. The supplementary data from the German study showing an increased mortality from lymphatic and hematopoietic cancers are more impres sive, particularly as the excess was the most marked for men who had been employed for at least five years. In these circumstances, judgment must still be sus pended until the data for each study are analyzed for each specific type of cancer, by intensity and duration of exposure, and by time since exposure began. There remains the suggestion that vinyl chloride might cause lung cancer. At first sight, this possibil ity is ruled out by'the SMR of 97 for the combined data for respiratory cancer for the four principal studies. Lung cancer is, however, normally so com mon (accounting for about 6 of the expected deaths) that an increase in mortality that was half as impor tant (numerically) as the increase in mortality from angiosarcoma of the liver might easily be overlooked (V5 tf/a confidence limits of the SMR 85--112). The in cidence of the disease varies moreover within a coun try. and there must be doubts as to whether the na tional experience provides a suitable reference for men employed in plants that are not evenly distributed about the country. In these circumstances (ttfcipannot exclude an occupational hazard unless lyd^Blkown that the mortality of the exposed mchjEgtfMpident or the factors that might be expeaedttjttippnce it if some of it were occupational in origin, namely, the intensity and duration ofexposure and the time since exposure began. It is not possible to examine these relationships in detail, as the reports do not provide all the necessary information. Such information as they do provide, which was summarized in table 6, supports the idea that exposure to vinyl chloride involves a small hazard of lung cancer. Taken in conjunction with the knowledge that lung tumors have been produced in sev eral species of animals exposed to vinyl chloride by in halation (29), it would seem that a small hazard of lung cancer probably did occur. The evidence is not, how ever, strong enough to conclude that it definitely did. If it did, the hazard was evident only for men who had been employed for many years at a time when expo sures of several hundred pans per million or more were common, and any persisting risk can be only minute and incapable of detection. The questions that have been left unanswered by this discussion might well be answered definitely if (i) all the exposed men could be followed to (say) the end of 1984, (ii) the investigators could present their data in comparable ways, taking account of duration of employment and time since first employment and presenting data separately for men first employed be fore (say) 1965 and between 1965 and 1974, and (iii) estimates could be made of the effect of correcting the results for each group or employees for the locality in which they lived and worked. Hazards to the general population As vinyl chloride has been proved to cause cancer in man and is a mutagen in laboratory experiments, it must be presumed that even the minute doses that escaped into the general environment from production plants or (in the early days of manufacture) from PV< materials will have caused some risk of cancer to the general public. These risks must, however, have been very small, as air concentrations of vinyl chloride, even within a kilometer of plants handling vinyl chloride, used to be (in or around 197$) of the order of 10 to 40 ppb (I, 3, 15), and this level is about one-ten thou sandth of the concentration that has caused an pationat hazard. It is obvious, therefore, that it would] be impossible to detect the risk of any cancer that might! be produced by vinyl chloride other than a risk ofl angiosarcoma of the liver, as it has proved so diffi-cult to detect any other risk among men who were ex posed occupationally. The position with regard to an giosarcoma "wily so rai to one of tl dioxide, an. annual incit In these cm In a man liv ride was use controlled n of he effec Several su whether any and Elinder vicinity of pi *nd Sweden *1(11) Toun. to thorotrasi with vinyl ch rkm of the p ?*.. 0) found M 12-year perio bved half a pUm.and, in toady et al ( tnbuied to an Ne living wit ing vinyl chi Um two studi. rmce of as m. rtose to manur bn colleagues, v *"* with ma referents liv. . d* netghborho. Itow York State fodution with \ looped the disease ' years, resp' this period The o< IS or mor of these environm t^VCmiyha "* public. it conci re cert sly by /. Recent tfcmdred me Rvalues b<lo\ rdree of five |20ppb(ir Oust in ' values w. Iwithputti r finite of i.. j mix over within a coon' whether the najference for men evenly distributed instances one cannot dess it can be shown men is independent wed to influence it i origin, namely, the eand the time since le to examine these *orts do not provide i information as they d in table 6, supports oride involves a small conjunction with the been produced in sev> vinyl chloride by ini small hazard of lung vidence is not, how* that it definitely did. mly for men who had at a time when expo* million or more were k can be only minute ;ft unanswered by this red definitely iT (i) all >wed to (say) the end uid present (heir data count of duration of ;*t employment and first employed bcuj and 1974, and (iii) effect of correcting the yecs for the locality in tulalion ved to cause dancer in <ratory experiments, it the minute doses that nment from production lanufaciurr) from PVC ne risk of cancer to the tsi. however, have been is of vinyl chloride, even landhng vinyl chloride, 5) of the order of 10 to I is about one*ten ihouhat has caused an occutherefore, that it would ofany cancer that might de other than a risk of s it has proved so diffimong men who were exisition with regard to an* SA^.ncoina of the liver is dilfcrcm, This disease is nor mally so rare that, in the absence of specific exposure .to one of the known causes (vinyl chloride, thorium [[dkuudc, and arsenic in pesticides and medicines), the ' incidence is on the order of 1--2 * J0-T (5, 8).* these circumstances the discovery of even one case an accident at the other. According to any reasonable criterion the hazard to the general public (if there is any at all) must be negligible (42). No other hazard to the general population, other than a hazard of cancer, can reasonably be postulated. 0 man living close to a factory in which vinyl chlo* was used in the days before exposure was tightly rolled may be regarded as presumptive evidence Summary '.the effect of environmental pollution. Several surveys have been undertaken to determine .whether any such cases have occurred. Saric et al (43) This paper reviews (i) the possible effects of vinyl chloride on the personal health of men exposed by virtue of their occupation (other than the early effects Elindcr & Pershagen (13) sought for cases in the ;kisity of plants handling vinyl chloride in Yugoslavia food Sweden and found none, in Holland Dalderup et lot (II) found eight confirmed cases not attributable of the very high concentrations to which men were ex posed when the industry uarfim developed -- uncon sciousness. cardiac MBa, and the characteristic "vinyl chloride illntis^^Kd (ii) the carcinogenic tborotrast or arsenic and could trace "no contact effects that might conemp be observed in the.genarfcb vinyl chloride," but they made no specific men* erai population as a result Or the widespread distribu 'Ison of the patient's place of residence. Baxter et al tion of vinyl chloride at a pollutant. The possibility : O) found 14 confirmed cases in Great Britain over a that vinyl chloride might act as a teratogen or might . 12-year period, one of which was in a man who had cause mutations in the germ cells has not been exam Irvcd half a kilometer from a PVC manufacturing ined, as the little evidence that has been adduced plant, and. in New York State over an 18-year period, relating to such possible effects has been reviewed else . Brady et al (5) found 19 cases that could not be at- where and the conclusion was reached that no such ef ` tributed to any known cause, live of which were in peo- fects have been demonstrated. pie living within a mile of plants manufacturing or Many groups of workers exposed to vinyl chloride using vinyl chloride. The overall incidence rates in these in the manufacture of VCM or PVC have been studied last two studies were not unduly high, but the occur since the carcinogenic potential of vinyl chloride was rence of as many as six cases among people living so first recognized. Some results have shown that occu dose to manufacturing plants is surprising. Brady and pational exposure can cause angiosarcoma of the liver, his colleagues, moreover, compared their series of pa and others 'have suggested that it may cause several tients with matched referents and found that none of other types of cancer as well. The actual situation can the referents lived equally close to a plant. Two of these be determined only in an examination of all the evi six neighborhood cases (one in England and one in dence, especially the combined results of those studies New York State) cannot be attributed to environmental (hat include a substantial proportion of observations Lv pollution with vinyl chloride, ns the men who devel on men more than 25 years after their first exposure oped the disease had lived near the plants for six and and cover a long enough period for more than 10 V* eight years, respectively, before developing the disease, of the employees to have been expected to die. and (his period is too short to allow for the necessary The results of four studies can be usefully combined Latency. The other four cases, however, all occurred for this purpose. They are two national studies, one after 13 or more years of local residence, and the dis from the US and the other from the UK. and two covery of these cases strongly suggests that pollution studies of employees in one plant in Canada and two of the environment around plants manufacturing VCM plants in Italy. The results of other studies from (he or PVC may have caused a minute hazard to the gen Federal Republic of Germany, Norway, Sweden, Italy, eral public. France, and Japan can be used only to provide sup . Current concentrations around plants handling vinyl plementary information. The many earlier reports of ..chloride are certainly much lower than (hose reported exposed workers in the US and the UK concern men eviously by (he US Environmental Protection covered more completely in the two recent national ency. Recent British measurements made within a studies, and their results serve only as sources of hy hundred meters of the VCM areas have given aver- potheses. values below the daily limit of detection (S ppb) Minor criticisms can be made of three of the four for three of five plants, (he readings at the two others most useful studies. They do not seriously affect the being 20 ppb (100 m outside the boundary fence) and value of the results, except that allowance has to be W ppb (just inside it) (47), although substantially made for the failure to determine the cause of 6.3 7* higher values were recorded on two occasions asso- of the deaths recorded in the US study. Three of the .oaied with putting one plant into operation and with studies use national rates to estimate the numbers of deaths that might have been expected to occur in the * The figure of t .4 10*' cited by Heath et al (21) seems to absence of any special occupational hazard, and the have been a misprint for 1.4 - I0-'. fourth (Canadian) uses rates for the province in which (he plant was situated. It must, therefore, be kept in mind that the rates used may not have been wholly ap propriate for the localities in which the plants were situated. This circumstance is potentially important for the US study, which covered workers in 37 plants, 22 of which were situated in the southern part of the country. The other less informative studies are, for the most part, open to more serious criticism, and the value of each set of results needs to be assessed separately in relation to each disease. The combined results of the four principal studies show that the SMR values, reflecting the ratios between the numbers of deaths observed and those expected in the absence of an occupational hazard multiplied by 100, have been (i) 77 for accidents and other violence, (ii) 84 for diseases other than cancer, and (iii) 102 for cancers other than cancer of the liver. All these results are what might be anticipated for an industry devoid of any specific occupational hazard. The low ratio for diseases other than cancer reflects the "healthy worker effect," which results from the selection process that inevitably excludes some of the less healthy members of the population from industrial employment and is compatible with a higher ratio for cancer, as the mor tality from cancer is not normally subject to such an effect, apart from the first two or three year? imme diately following the start of employment. The mortality from cancer of the liver was nearly seven times that expected. Most of the 51 excess deaths were known to be due to angiosarcoma, even though this diagnosis was not recorded on the death certifi cate. The excess corresponds closely with the 49 deaths due to angiosarcoma reported to the International Register of Angiosarcoma Cases as occurring in em ployees of the plants concerned during the periods under observation. All the men who developed the dis ease were likely to have been exposed to concentrations of vinyl chloride of several hundred parts per million or more. Three other types of cancer which have been sug gested to occur as a result of exposure to vinyl chlo ride are cancers of the lung, brain, and lymphatic and hematopoietic systems. The combined data for the mortality from respiratory cancer fail, at first sight, to support the hypothesis regarding lung cancer (SMR 97). Higher ratios for lung cancer have, however, been observed consistently in the subgroups in which the effect of an occupational hazard would be most like ly to be seen (that is, men employed for more than 10 years, exposed to higher than average concentrations, or observed more than 20 years after first exposure). In two of the supplementary studies it was also noted that the mortality from lung cancer was specifically increased among the most heavily exposed workers. The combined data show small excesses in the mor tality from cancers of the brain and of the lymphatic and hematopoietic systems. The excesses are, however, not statistically significant, and there is nothing to sug gest that they are occupational in origin. An excep- (ion is the observation of an increased mortality from cancers of the lymphatic and hematopoietic systems- in the supplementary study from the Federal Republic of Germany. Two types of cancer were reponad riHl in excess in the Norwegian study, namely, ftj<Mpttcer and melanoma. The significance of difficult to assess because very little information about these cancers has been provided by other studies. Suggestions that vinyl chloride might cause cancers of the digestive tract have failed to account for the contribution of angiosarcoma of the liver. When this disease is excluded, the mortality from digestive tract cancer decreases to below the average (SMR 82 for the four principal studies). A small excess mortality from the heterogeneous group of "other cancers" in the combined results of ihe four principal studies was statistically marginally significant (83 deaths against 65.25 expected. PcO.OS). Some of the excess was likely to have been due to the misclassificaiion of angiosarcomas as secondary can cers of the liver or carcinomatosis, site unknown. The following three nonmalignant causes of death have required special examination: cirrhosis or the liver because of damage to the liver in "vinyl chloride ill ness, " myocardial infarction (from analogy with the effect of other halogenatcd hydrocarbons and because- of some observations from Swedish PVC fabricators), and nonmalignant respiratory disease because of changes in lung function and (he radiographic appear ance of the lungs observed in men exposed to PVC dust. Far from being raised, the mortality from cir rhosis of the liver was less than expected in the three principal studies and in one of the two supplementary studies which gave separate figures for the disease (SMR values of 69, based on 46 deaths, and 82, based on 15 deaths), while in the other supplementary study the increase was trivial. Data for myocardial infarction have not been re ported separately. But myocardial infarction accounts for most of the deaths attributed to ischemic heart dis ease, and there is no evidence that either ischemic heart disease or cardiovascular disease as a whole was un duly common (SMR values of 90 and 92, respective ly) or related to occupational exposure. The data for the third category of nonmalignant dis ease (nonmalignant respiratory disease) arc confusing, because the two large national studies give conflicting results. The combined data for the four principal studies show the low mortality that is commonly found in healthy industrial populations (SMR 80). This fig ure hides, however, an increased mortality from chronic obstructive lung disease (SMR 120), which in cludes emphysema and is due to a grossly increased mortality attributed to emphysema in the US study (SMR 193). The corresponding mortality in the British study, which was preferentially described as due to bronchitis, was less than expected (SMR 82). as was the mortality from pneumonia (SM It SO) anil other rcs- 76 Sgt - *. ftftfory disea no consistent fe. fbywinn or b It seems i T USfludy was !>; Bn with the u Review of t t-r. fewg-ferm hea vmyl chloride have expe: : extremely rare *msdy I in 33 tftdicd died of Y *he observed d< of lime the nu be expected to dtf mortality I of that of nom hazard has ext The data prt zed other than ft. however, sti> nie produces si dor to nonoccu fe**r, and, if st cause almost as brr. There is too li she suggestion t poma or cancer and hematopoie that have been n pntlonal hazard, dmofthe lymph 'German study re> .wet of chance eii\ many types of ca dadics. /..The lack of an nrbithecombin does no e been a sma disease, as gt the disease th I rates foi .The great! dbemoreli. other group existed. The cnee of a ha [Clearer answer posed in th I groups c s in more a " At vinyl chlorii wnti ami a pro* that have es . ^illuiani-. mti-. - itimuii- 11 alily from >c systems I Republic : in excess rancer and is difficult bout these es. use cancers un( for the When (his testive tract R 82 for the erogeneous -d results of ' marginally d, P<0.05). n due (o the ondary canunknown, ises of death >s of the liver i chloride illlogy with the and because ' fabricators!. 1 because of iphic appear ed to PVC ility Trom cird in the three upplemrntaey ir (he dtse^ic and 82. basSf mentary stu% I Il i i ! r i e not been re elion accounts' lemic heart disischemic heart whole was un92, respectivere. nmalignant dis* ) are confusing, give conflicting four principal ommouly found IR 80|. This figmortality from l 120), which in;rossly increased in the US study ility in the British cribed as due to SMR 82), as was 50) and other res- \ piratory diseases (SMR 46) in the US study. There is no consistent evidence that the mortality from em physema or bronchitis was specificaHy occupational, and U seems possible that the reported excess in the US sludy was an artifact due to nosological difficul ties with the use of the seventh revision of the ICO. Review of the massive data now available on the long-term health of men occupationally exposed to vinyl chloride leads to two dear conclusions. First the men have experienced a specific hazard of the normally extremely rare angiosarcoma of the liver. Approxi mately I in 335 of the men exposed in the 49 plants studied died of the disease, and approximately 2 % of the observed deaths were attributed to it. In the course of time the numbers of cases of angiosarcoma must be expected to increase two to three times. Second, the mortality from all other causes has been typical of that of normally healthy industrial workers. If any hazard has existed, its effect has been small. The data provide no reason to think that any haz ard other than one of cancer has been overlooked. It is, however, still difficult to decide whether vinyl chlo ride produces small risks of cancer, compared to those due to nonoccupatioiial causes, at sites other than the liver, and, ir so, whether, in total, these risks might cause almost as many deaths as angiosarcoma of the liver. There is too little evidence either to confirm or refute the suggestion that vinyl chloride might cause mela noma or cancers of (he thyroid, brain, and lymphatic and hematopoietic systems. None of the small excesses that have been recorded poim specifically to an occu pational hazard, apart from that attributable to can cers of the lympharic and hematopoietic systems in the German study reviewed, and most are likely to be the sort of chance effect that is certain to be observed when many types of cancer are examined in many different studies. The lack of any increased mortality from lung can cer in the combined results of the four principal studies reviewed does not exclude the possibility that there may have been a small occupational hazard of developing the disease, as geographic variations in the incidence of (he disease throw doubt on the validity of using national rates for estimating the expected numbers of deaths. The greater mortality in groups of workers who would be more likely to show an occupational hazard than other groups suggests that a small hazard may have existed. The evidence is, however, weak, and the existence of a hazard has not been proved. Clearer answers to some of the questions that have been posed m this review might be obtained if the various groups of investigators could present their results in more appropriate and comparable ways. As vinyl chloride is a mutagen in laboratory experi ments and a proved human carcinogen, the minute doses that have escaped into the general environment as pollutants must be presumed to have caused com parably, minute risks to the general public. No such risk could possibly be detected, other than one of angiosarcoma of the liver which is normally an ex tremely rare disease. Several surveys have sought evi dence of the existence of such an effect, and sugges tive evidence that such an effect may have occurred at a time when environmental pollution was much greater than it is now has been found in one. References 1. Air Products and Chcmkals. Inc-Commcnu on the pro posed standard for vinyl jMMMe. Letter to Oft Goodwin. Envirornnem^flHHBB Agency, Washing ton, DC 23 September In an unpublished report by Barr to Air PigiMjlS^p Chemicals, inc, in 2. Baser ME, Tockmsn MS, Ifomedy TP. Pulmonary function and respiratory symptoms in polyvinyl chlo ride fabrication workers. 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Received for publication: 16 February 1988- 1 Epidemiolog Institute Ari Canada. 1 Department < versity, Mon * Department UEM- 239248 University or Reprint reques cm epidemiolo) I lappier, 531 1 Canada. 117V I