Document MGopr182qbGyQ3OGrRgMQ6QE7

Five Executive Mjtl. Sa''iI r.fonl Road, Wayne. Pii. 19037 April G, 1976 / Mr. J. R. Smith Special Studies Staff Enviror.montal Protection Agency National Environmental Research Center Research Triangle Park, North Carolina 27711 Dear Mr. Smith: This will furnish you further information on the subject of reported nonpolymeri zation worker cases of angiosarcoma v/hich we discussed by telephone on March 31 and April 2. Some confusion seems to have arisen over the nomenclature applied to the reported cases of angiosarcoma irt Connecticut. They have been variously called "community cases" cr "neighborhood cases" in the media, in EPA documents (STAR Document, p. 1), and in the ERA hearlnq (cross-examination of Barry Castleman by Dr. William Marcus, hearing transcript p. 2, ccpy attached), "non-polymerization cases" by KIOSK, and "non-occupational cases" by CDC and in other places.Unfortunately, we seem to have added to the confusion by using both "non-occupations!" end "non-polymerization" on page 19 of the Air Products' submittal to Dr. Goodwin, dated February 23, 1976. t will hereinafter use the NIOSH designation of "non-polymerization" for employees not working in PVC plants and "non-occupational'1 for oursons not employed in any part of the PVC industry. The cases with which we are concerned are therefore "non-polymerization" cases. NIOSH does list these in "Table II" which they maintain. The latest listing cf these cases is dated September 12, 1976, and is attached. It has not bcon distributed routinely with Table I over the last few months, and Drs. Adams and Smith of this company were informed earlier this year by Dr. Lloyd that it had been discontinued. This led to the statement in the submittals by Air Products and the Society for the Plastics Industry that these cases had been dropned. In a conversa tion today with Dr. Pierre Decaufle of NIOSH, he confirmed that this list is not normally distributed now, but that it is still in existance and will be maintained. The burden of proof is on NIOSH to substantiate their listing of these cases, and to show their relationship to vinyl chloride. No one presently exercises this responsibility. Anqiosarconas dp occur in populations not exoosed to vinyl chloride. The CDC has recently published a survey of ten cases in Wisconsin which have no vinyl chloride relationship whatsoever (cony attached). The Connecticut cases would seem to fall into a similar classification except for the very casual relation ship to fabrication operations. This type of correspondence is expected to occur on a statistical basis from time to time. AP00048807 Hr. J. R. Smith 2- April 0, 1976 Regarding the foreign cases listed In NIOSH Table II, Germany 01 filled aerosol cans where the exposure from leakage was reported to be hiqh. We have no more information than NIOSH on Germany 07, or Great flritian 02. Italy 01 did not have primary liver angiosarcoma. Sweden 02 worked in an obsolete acctylene-process vinyl chloride plant where the exposure was high. The two U. S. (Connecticut) cases are discussed by you in the footnotes to Table 6-19 of the STAR Document, where you quote Dr. L. 8. Thomas of the National Cancer Institute. He states that both cases are uncertain. Furthermore, ERA has stated that their measurements of vinyl chloride around fabrication plants show it to be "almost negligible11 (Preamble to Standard 40 FR 59534). The highest found was 6 ppb, and none was found at 3 of the 5 plants tested. Thus, these "nonpolymerization" cases are doubtful in relationship to vinyl chloride, and do not support any concern for harm at "levels of exposure as low as 1-10 ppm1' (STAR Document, p. 1). The exchange between Hr. Castleman and Dr. Marcus at the EPA hearing indicates that the EPA has reached the same conclusion. This is supported by the statement In Appendix E, page 5, of the Risk Assessment Document by A. M. Kusmak and R. E. McGaughy that, "This survey has produced no evidence that living around vinyl chloride plants is a risk factor in the occurrence of liver angiosarcoma." Thus, we stand on our position that there is no demonstrated risk to persons not exposed to high concentrations of vinyl chloride for long periods of time, and therefore the proposed standard is unnecessary. I hope that this clarification is of help to you, and apologize for any confusion to which we may have contributed. We will be happy to discuss any other part of our comments with you whenever you may wish. Very truly yours, AIR PRODUCTS/^ CHEMICALS, INC. 0TB:mjv Technical Manager Attachments cc: Mr.' G. Baise, Ruckelshaus, Beveridge, Fairbanks & Diamond, Wash., DC Dr. D. R. Goodwin, EPA, Research Triangle Park, NC Hr. J. Hadley, Keller i Heckman, Wash, DC Mr. R. Harding, SPI, New York, NY bcc: A. R. Adams R. Fleming R. H. Schenck W. M. Smith L. B. Tenner AP00048808 TRANSCRIPT OF EPA HEARING OM HlYl. CHLORIDE, FERRHARY 3, 19: nn. ?'Ar.CUfr.: Po you knew of: any evidence of the increased rink in the general population, other than the studies that have been dona in work? ; UK. CASTTl'KAH: Aside from the fact that there were apparently two neighborhood canes with no known occupational o^ocuro, no T dorr't. DR. MARCUSs T would like to say that EPA investigated very carefully those cases, and wc consulted with our expert doctor, Hans Popper of Mount Sinai, and it was his expert opinion that these people did have ir angiosarcoma.- that wfio of a diffcrnt type then that caused by vinyl chloride monomer, and'I i/.ust say, to date we do not have any evidence that angiosarcoma has been produced by vinyl chloride monomer in the general population. HR- CASTLEJIMI: I think it is important to realize that only about one-fourth of the present PVC plants V7cre operating 20 years ago, The latency of -this disease is 20 years or more, and of these ten plants, at least one-fourth of the present level of plants, which is about ten, the total production rate is one-tenth of the i vate it is today. The population nay also have been thinner | around the plants than it is today. i So, if you look at the j>x'esent situation in terms of how many people lived near the plants of a certain j size, it bears little resemblance to the situation 20 ' A ! I . S> ' AP00048809 years sqo. The mortality experience that t."o observe today started 20 years ago. I don't think the absence of canon in any proof of anything. Wouldn't you agree with that? DH. MARCUS: In general X would nay that ia a very cogent comment. The only thing here is that vinyl chloride happens to offer us a unique opportunity to sec an extremely rare cancer, which we can say is maybe due to the substance in question, rather than an increased rate of cancer, which ic a very difficult thing,to assess. That in why I say, I was hoping somebody would have some information about VCM induced angiosarcoma in the general public, because we have not been able to find it as yet. - fra. CASTLEMftM: I talk to the came poc-plc you do CHAIRMAN Dmp'r.y: nr. McGnughy. DR. MC GAUGirv: X just have- one short cruestion. *7e are interested in getting as accurate a picture as v;o can as to what the risk is to the population due to vinyl chloride exposure. You mentioned there were two or three factors that vs have not considered. Mainly tho carcinogicitv of7 vinyl chloride and other chemicals and the Lransplnnecnta]. effects that might caused to expectant mothers. AP00048810 A P 0 0 0 4 8 8 11 NIOSK September 12, 1975 TABLE II REPORTED CASES OF ANGIOSARCOMA OF THE LIVER AMONG KON-POLYMLRIZATION WORKERS EXPOSED TO VINYL CHLORIDE COUNTRY CASE ff Fed. Rep. Germany Fed. Rep. Germany Great Britain Italy Svecen United States United States 03* 07* 02* 01 02* 14 15* BIRTH DATE 07-16-30 05-09-36 09-08-14 06-15-34 11-27-11 00-00-13 00-00-25 1st VC or PVC EXPOSURE 06-09-52 00-00-60 00-00-46 OO-OC-65 00-00-45 08-18-38 00-00-00 DX ANGI0 SARCOMA 03-00-73 00-00-74 02-00-70 04-19-71 05-15-72 06-00-73 07-00-72 AGE AT DX YRS 1st EXP TO DX TOT YRS EXP 43 21 38 14 55 24 36 6 61 27 60 36 47 00 14 03 . 11 3 23 00' CO DATE OF DEATH 10-10-73 12-16-74 12-00-70 04-16-71 08-16-72 07-03-73 02-15-73 Note 6 Note 9 Note 1 Note 2 & 7 Note 3 Note 4 4 8 Note 5 Note l Note 2 Note 3 Note 4 Note 5 Note 6 Pouring PVC oil fixture onto fabric bases Production of PVC sacks Production of Vinyl Chloride Machine operator covering electrical wire with PVC plastic insulation Accountant at plant ranking PVC fabric Loading pesticide cans with VC propellant Note 7 Note 8 Note 9 Angiosarcoma involving liver, lung, and pericardium. Although difficult to determine, primary site seems to be pericardium. Diagnosis: Sarcoma (possibly "angiosarcoma"), liver. Possibility of generalized neoplasm of the reticuloendothelial cell system cannot be ruled out. Assistant Factory Chemist * Indicates microscopically confirmed angiosarcoma of the liver. "00" Indicates unknown data. j ri KED2CHEM UfTEILN'ATICNAL CafFESSNCS HAIFA, ^ISRAEL 7-10 SEPTS?*I32R, 19 76 Institutional Interactions in Problor.s of Occuraticn^l Health: An Industry View cn the Logsdons fro:,i Vinyl Chloride by A W Earnes ICI Plastics Division AP00048812 / Tnf>titnliori-Ml Interactions in Problem of Occupational Health: An Industry View on the Lessons from Vinyl Chloride A W Barnes I hove been asked to speak this morning about ''Institutional interactions in problems of occupational health". The views I want to express are personal ones: they derive solely from my personal experiences over the past 2} years when I was closely involved with the vinyl chloride problem. My involvement, and that of my colleagues in the general management of the* European PVC industry, was in part as a 1 Syrian in a highly speciolised field where the initial contributions had to be made by experts and professional people from universities, government end research associations. As industrial general managers, and with our trade union colleagues, our prime responsibility was to see that all possible steps were taken at the maximum speed to ensure the safety of the plant workers: ultimately though I believe we also made some contribution through our experience in bringing together the views of experts in different specialist fields, because, as generalists, the critical appraisal and pulling together of expert opinion is part of our normal daily jobs. Once our colleagues outside industry had found that our objective was precisely similar to theirs - i.e. the full safety of our workers - the result was an enormously fruitful co-operative effort involving everyone who could help. Indeed, if it were not for the personal tragedies which preceded and initiated all this effort, we would have good reason for feeling entirely pleased with the way groups of people from different disciplines and countries, from different institutions and with different responsibilities, came together to solve an immensely difficult problem. Of course we had our difficulties in the early days. Industry seems nowadays automatically to be cast in the role of the villa.n of the piece by much of the media, and a suspicion that this might be true exists in the minds oven of reasonable people. Our first task therefore was to convince people that we were just as concerned as they - perhaps more so to 6cc that our staff worked under safe conditions: but this was not too difficult since the statement was true, and the people we were involved with in government, universities and trade unions were willing to listen, and then to observe that our actions confirmed our vords. Another difficulty initially was the belief that this was a rac-dical problem and that only doctors therefore could speak with authority, even when it came to framing legislation. But a doctor is not a lawyer nor yet an engineer: nor is he an expert on industrial control processes or analytical techniques; arid rnroly do wo find, in any one doctor, an expert epidemio logist, toxicologist, oncologist, clinician and statistician combined! ' Yet all these and many other disciplines were necessary for the definition of the problem nnd for its resolution; and some of these resources industry could provide. The barriers between the medical profession and industry were real and potent because they prevented, initially, the dialogue which alone could lead to a full understanding of the situation: but with goodwill they were broken down nnd hive led, I believo, to enhanced mutual respect and indeed to many lasting friendships. AP00048813 a One of the bigger problems, which persisted throughout the period, was the effect of reports and comment from American sources. The character of come of these cu:ne as a total surprise and one of the major lessons many of us learnt from the vinyl chloride problem was that American information liad to be treated with extreme care. America is enormously important because of its resources, and its influence throughout the world; but its method of debater matters of public concern is very 1 different from the custom in Europe. The glare of publicity which attends these debates certainly seems to encourage some scientists to speak out with a certainty that is hardly justified by the quality of their information. V.'hatever the reasons, many American reports were of doubtful validity because they frequently gave information which was incomplete or unconfirmed or simply inadequately analysed. Their imjjact nevertheless was major: by heightening the feeling of alarm, they increased the pressure on European institutions to take up extreme positions, as in the USA, and this, if it had happened, would have made co-operation and rational analysis extremely difficult. Fortunately it didn't happen: medical institutes, government departments, trade unions and industry realised that, while* taking full note of US information and comment,- their proper task was to develop a European response, independ ently, to the problem. In this context it is interesting to note a remark by Dr Marcus Key, who was director of HI05H at the height of the vinyl chloride crisis* Speaking at the Royal Society of Medicine Conference in September 1975 he commented that in Europe we seemed to have reached roughly the same end point as the USA v/ithout the tensions and trauma surrounding the generation of the GSIIA regulations. Kow did we achieve this, first nationally and then internationally in Europe; and how did representatives of institutions from many different nationalities end with widely different interests and experience learn to work together? At tho national level, I can speak more knowledgeably of the UK, although similar processes, I know, developed in the rest of Europe. At an early stage in the UK, the government set up a Tripartite Working Group composed of senior representatives from government, the trade unions and industry- It is important to note that, at no point, did this become a negotiating body made up of throe factions. From the beginning, it was one group with a single common purpose: it owned the problem as a group and it was committed, as a group, to the solutions it developed. This attitude is well exemplified by one of its actions: a smaller tripartite group was formed from the raisin committee to visit all the UK PVC plants. The purpose of this was not to check that management was doing the right things - though we had the opportunity of seeing this too - but to allow everyone on the plant, from: works manager to plant operator, the opportunity of checking that we, who ultimately had to recommend standards and codes of practice, were doing our job prooerly. On each visit an open forum was hold tc allow the works staff to fire questions at us so that they could determine to_their own satisfaction that we knew what we were talking about. The standard of debate and of information throughout was at an extremely high 'level: and a very important result of the visits, was that the tripartite group nnd the workforce throughout tho industry were very firmly united in a common endeavour. Internationally, tho European FVC industry formed a scriec of vinyl chloride committeen under the auspices of CEFIC (the European Council of Chemical Manufacturers Federation:;); and within the:.a committees a groat deal of co-operative work wan done in both the technical nnd medical fields. An a AP00048814 3 result of thin, representative?; of the rain committee were able to speak wilh authority for the whole of Europe whenever a contribution from industry war. required. This was no mean achievement, for Ua.fiische and ICI and Solvay and Montedison are just as nuch institutions in their own right as is the University of Louvain or the University of Wurzburg ' ^or the Mario Uegri Institute. But one of the most constructive of European moves was the invitation to CEFTC from Directorate General V of the Commission to join with their Ad-Hoc Committee on KAK values in considering and advising on a possible Commission directive. This committee was composed largely of distinguished medical academics and the. meetings provided the first opportunity for a dialogue between European industry and the European medical establishment as well as with the Commission itself. Of course there were some mis understandings initially, for industry was talking the language of science and technology while our colleagues were talking the language of medicine. As an example may I quote the initial belief among our medical and commission colleagues that if a directive were to lay down a maximum of, say, 10 ppm (averaged over any,8-hour period) then industry would be able to operate at a constant level of 9.5 ppm. They had not appreciated that the products of industrial processes are rarely constant day in and day out, and that there is always a variation about a mean. Because of this, for 10 ppm never to be exceeded, plants must be operated, on average, well below 5 ppm and will frequently be producing results of 1 or 2 ppral So a legal requirement for 10 ppn not to be exceeded, is very close to a medical requirement that average exposure should be below 5 ppml Fundamental difficulties of this type were relatively quickly sorted out however because of the willingness of members of the committee to meet and discuss the problems on an individual basis. For instance, Professor Kaltoni from Italy and Professor Lauwerys from Belgium paid day-long visits to ICPs plants in the UK and Professor Foa arranged for one of his Italian colleagues to visit us also. Similar exchanges occurred in the other countries of Europe and, quite soon, we were all talking a common scientific language and progress was rapid. Within DGVI of the Commission initial progress was not quite so positive. This Directorate-General, which was concerned with the control of PVC for packaging foodstuffs, also remitted the problem to its scientific advisory committee but unlike D3V made no formal invitation to industry, or other interested parties, to contribute. The committee, composed 'largely of toxicologists, had the impossible task of proposing control levels for vinyl chloride in foodstuffs, where the human exposure levels were already a million times lower than any level, at which carcinogenic effects had been observed. Hot surprisingly, their conclusions could owe little to toxicological data; and in an understandable effort to ensure the absolute maximum in safety while still, they believed, supplying a practicable solution, their first proposal was that "vinyl chloride should not be 'detectable in food or potable water by an agreed method. Attempts should be made to develop generally applicable analytical methods with a sensitivity of the order of 0.001-0.002 mg/kg." An obvious philosophical objection to this early proposal wa3 that it related the control level simply to the stale of advancement of analytical science which of course is in no way related to the question of hazard from vinyl chloride. Of t-von more concern to industry, though, was that AP00048815 it was o totally impracticable solution fnnee the problem af variation of results about a neon hnd again been overlooked; and the problem here was complicated further since vinyl chloride reaches a foodstuff by a slow diffusion process. In addition to the normal variation in any industrial process, which is to a decree controllable, a further factor therefore is the period of storage of the product, which is not. To ensure a non-dctcctable amount in any foodstuff at any time, it would be necessary to control at the factory or packing station at a level say of l/70th of noil-detectable! A moment's reflection will make it clear that this is somewhat difficult to measure! - and therefore impossible to ensure. Effective control of an industrial process demands the facility to measure key parameters of the system while they are still within specification, so that any trend away from the norm and towards the specification limit car. bo detected and then corrected. Our concern, within industry, was such that the CEFIC committee produced a discussion paper which some of you may have seen. It is the only document I know which attempts to bring together, in an orderly fashion, all the facts and factors relevant to a particular aspect of the vinyl chloride story. Its purpose was to encourage debate on matters of judgement and, if necessary, to allow argument in areas of disagreement but always disciplined by facts and figures. I believe it has proved of some value and that in this part of the vinyl chloride problem - as in that concerned with worker protection - real progress became possible once v?e had found a way for medical experts, government representatives and industry, to challenge and to educate one another in rational debate. These are but a few examples of how, in Europe, we learnt to work together. In all they add up to a story of some considerable success: but before v/e get too complacent I think we have to ask the question "Did^we^do^- have we done - all we could?'1. I'd like to SDend the rest of this**papcF^in^ explaining, as a layman in a medical fiela, way X believe we have not. It seems to me that vinyl chloride is almost unique among known human carcinogens. Our knowledge of its effects on animals, through the distinguished researches of Professor Maltoni, is moru extensive than for many, perhaps most, other carcinogens; and our knowledge of its effect on humans, because of the rarity of angiosarcoma of the liver, is in almost all cases precise and unambiguous. It must be rare to find so clear-cut an effect on a human population in conjunction with such thorough animal experimentation. I would have expected that the data on vinyl chloride would have been seized upon to see what more it could teach us about carcir.ogonicis in general. But what we have had is a flood of ropers on epidemiology by epidemiologists, on toxicity by toxicologists and or. metabolism, clinical treatment, immunology, chromosome aberration, etc. Any attempt at nsalvnis nf the .e-Lta on i\ world scale has been minimal and most references to i ro lessor .kaltonz s worc have necn liiuitoo to w. superficial treatment of the results from his experiment BT1. It is indeed btnrtling to observe that, from all of Professor Maltoni1s massive research, the only conclusion that has actually been used in the field of industrial hygiene is the conclusion that vinyl chloride is a carcinogen. As an employee of one of the companion who sponsored Knltoni's work, I feel bound to ask whether the cost nnd effort, on our part and on his, was worthwhile if this isS the only u.'oful information wc can extract. AP00048816 5 Why has the yield been cb poor? Could it be that the medical profession itself ir. getting a little over-specialised and that vinyl chloride has been seised upon by the specialist as a useful vehicle for testing out theories and advancing knowledge in his own specialism? Is it possible that rather more interaction is rcquii'cd within the medical profession and that ve reed the interest of one or two good medical "generalists" who can pull together al.,1 the data and begin to answer some of the outstanding questions? Only you can say whether these are foolish questions or 'whether they are worthy of some consideration. But tho fact remains that there arc questions still to be answered. General to the whole problem of carcinogenesis and toxicity is the relationship between the results of animal testing and the effect of the toxic substance on humans. How many times in the past years have I heard, the remark that we don't know how to relate the one to the other; and while vc remain in this ignorance the value of work like Professor Kaltor. is diminished. I cannot help feeling some surprise that there has been so little effort to analyse the human data on vinyl chloride and to relate this to Professor Haltoni's comprehensive findings. Of course any relationship ve find for vinyl chloride will not provide the key for all future problems but it would at least be one more step along the road of understanding. There remain specific to vinyl chloride, which demand more application by all of us. The first asks whether there remains any risk to tho^consumer^from food, wrapped in PVC, at the infinitesimally sTifalT'Tevels "oi^inyi^clilorlde vdiich can still be detected: and if so, what the level of risk is. The problem for toxicologists is that there is no experimental animal data on vinyl chloride at the minute exposure levels we are talking about: but even if there could be, they would still be faced with the problem of relating rats to humans and this is a permanently insoluble problem if we confine our studies to evidence from ingestion. There would be no possibility of obtaining convincing human ingestion data even if the risk were a significant one ~ which is of course completely contrary to our belief. Yet, tantalisingly, there exists a great deal of data on the effect of inhaled vinyl chloride, on both rats and humans, which, as I've already indicated, could give us some pointers to the relative sensitivities of the two species. The need is to achieve some definition, albeit imprecise, of a risk; for in matters of public concern qualitative generalities have little - or too much - impact depend!:, on the speaker. The problem is to find some woy of bringing nil the results together to bear upon the question. Within industry, we were greatly indebted to ny colleague Dr K S Williamson who pointed out that nil known results, inhalation, ingestion, human and animal, could bo examined in one table by defining exposures in mgra/kgm . of body weight; and that, when thin was done, a degree of consistency could be observed ucrocs all the results. Starting from these unified results, and with the help of published work by Schneiderman, Mantel and Bryan and the late Pr Leo Friedman (this Inst incidentally in a very relevant WHO report which has received surprisingly little attention) the CLtTC discussion document was able to suggest c. value for the maximum residual risk from foodstuffs of the order of 1 x 10"or come 60,000 times lower than the risk, calculated by Friedman, arising from the cons-rr.p: of 70 grin of "charcoal-broiled" steak daily. The analysis wo have done is an elementary and quite unsophist i rated one.* our answer ia certainly imprecise - how could it be otherwise at*these levels? - but wherever wc AP00048817 6 have had to make assuraptions of our own, rather than drawing, oa the published work of j-.pocia3.intG in the field, we have tried always to be conservative. What is disturbing to nc id that I know of no other published attempt to dctox'rnine the order of magnitude of the risk* I recognise the icjner.se difficulty of being able to speak with certainty when results have to be . extrapolated over at least six orders of magnitude. But where the need is great, some effort should, be made: in its absence the discussion is left vide open for pure speculation undisciplined by any facts* So far I have discussed two problems which require us to apply each more thought to the relationship betv/een Halt.oni's animal results and the known human data. A third problem exists which is, for industry, much more important than the previous two and which concentrates our attention exclusively on better analysis of human information. v Throughout the past ?.*r years one group of people has shown a maturity and a sense of responsibility and of determination which is an exaiiple to the rest of us. This is the industrial workforce actually engaged or. producing PVC. Clearly all of us - medicals, engineers, chemists, legislators - had to establish conditions which were safe for work, out, with that achieved, our obligation to the work people is not yet fully discharged. Ve, and they, know that, in the future, there will be further cases of ar.giosarcora of the liver among vinyl chloride workers, deriving from the higher exposures of earlier years. When these occur, there will be an inevitable diminution, in their sense of security) and doubts will naturally arise, for them and their wives and families, about the effectiveness of the new safety measures. If this happens, we who helped to devise the res,Jlat*on3 v/iH net have dor.e our duty if we can only reproduce the same qualitative reassurances that we were using in 1973 and 197A-. With the finalising of regulations around the world the job - for doctors, administrators, statisticians ar-.d general, managers - is not finished. We must be in a position to reassure too sc cost directly concerned that we have done our job well; and this requires us to pursue our research and our analyses further and further towards a quantitative conclusion. What, you may ask, can be done? I'd like to devote the last section of this paper, to a brief review of what has been done on data analysis ar.d then 'o suggest a scheme for further work. These latter proposals derive from nar.y discussions I have had with tr.y colleagues Dr Williamson and Dr Paddle of *.CI who would be much better equipped to present them today: I must present ".hen in simple layman's terms for that is the only way I know. Jntil early 1976, the only formal document which surveyed the world data on the effect of vinyl chloride on humans was the NIOSK list of angiosarcoma cases among vinyl chloride workers. But this war. only a list; no analysis tf any kind was attempted. In April 1976, the CEFIC document, to which I have already referred, made * a first step in classifying the human data. It listed the cases according to the particular plant on which they occurred; and it summarised its findings in the following (up-dalcd) tabic. AP00048818 7 Humber oC A/S Punthc,/PJ.ant 10 9 5 each 2 each 1 each 50 Ho cases reported TABLE 1 Humber of Plants. 1 1 2 6 1? 23 --20 plants with >20 years life Location of Plant USA Canada f USA Germany, Sweden, rrar.ee + E Europe USA + Europe Many of us believe that this rather puzzling distribution can only be explained on the basis of differing exposure levels, many years ago, frert one plant to another and that this is the first indication that some sort of dose-response relationship might be deduced for ran. If^i.t^-d-p^s and Maltoni has ccrtr.LnlY.drm.oDStrated one for rats - theh've should be aGYi^g all we can to doterrnne it. Eeiore considering how tms .v.igiit be do'Xetf4US'hseS'`'witct'lier tjhe*'"'Jrude data car. tell us anything else. If the deaths are tabulated, by year of death (where we know this) we get the following information. Years of Deaths TABLE 2 Numbers of Deaths in Period Average Number of Dcaths/Year Before 1961 1951-65 1966-70 1971-75 1976 so far 0 2 10 24 4 0 0.4 2.0 4.8 >4.0 40 At first sight this is alarming since the number of dcaths/year appear to * be on a rapidly ascending curve; but before we proceed, it is worth looking at another classification, which I have not seen published elsewhere. If we group the deaths according to the year of first exposure, wo got results which I have summarised in Table 3* AP00048819 8 Yenrc of Firr.t Exposure 1943-54 1955-66 TABLE 3 Number of Core;; Latency Period from First Exposure (a) Range (years) Cb) Number of' Cases With <15 Years Latency 28 15->32 14 9-20- 0 8 In the second of the two 12-year periods the fact that we have no latency periods > 20 years is not of course surprising. The elapsed time has not yet been sufficient for longer latencies to appear; and regrettably we must expect further cases tb arise- What'is interesting, however, is that 8 out of the 14 cases in this period have latencies less than 15 years whereas, in the first period, no latencies as short as this have been reported. It seems difficult to believe they did not exist: indeed this analysis seems to provide the clearest evidence yet in support of the suggestion that, prior to 1961 and possibly later, deaths from angio sarcoma were under-recorded.. We can best see where this takes us by looking at some simplified graphs. If we plot actual numbers of deaths per year against the year, we get the following picture (Figure 1), which is disturbing if true. SQi $ S3 o 1956 53 60 62 64 66 68 70 72 74 76 78 80 82 8-* 86 YEAR AP00048820 9 However, we have seen that early deaths are probably under-recorded, so the real line han, almost certainly, a lower slope than this. Further, the industry, and the numbers of people becoming at rick each year, grew rapidly in the 1950's and l^'bO's so that if we were to plot the incidence of deaths, i.e. the number of deaths each year as n proportion of the population at rick, say 20 years earlier, then we would expect the righthand side of the graph - and its extrapolation - to decrease rplative to the earlier years. A further factor still is that exposure levels have steadily decreased over the past 20-30 years, from values of possibly 1000 ppm in the ^O's and 5^'r. to values below 200 ppm in 19731 immediately before the recognition of vinyl chloride as a human carcinogen. Since we believe there is a dose-response relationship, these changes should result in a decreasing incidence by the late 1970's. By 1?35 the effect: o: the latest standards should be quite marked; we oust expect, still, some 30 year latencies dating from 1955 v(but what about Kaltoni's B73 results?) but there ought to be no 12 year latencies dating from 1973 and 1 hope there will be few 20 year latencies dating from 1965* Figure 2 shows the original line of Figure 1 with arrows suggesting likely changes because of the factors listed above. A very notional revision is indicated by the dotted line. AP00048821 .10 Can we get a better idea of where this new line really is? As an amateur who doesn't therefore nee the difficulties nay I suggest (a) that our statisticians night be able to give sooe estimate of the number of missing casco in the early years and (b) that industry, with some difficulty, ought to be able to estimate the yearly populations at risk. To estimate the effect of reduced exposures, we need to know what the exposures have been over the whole period and we need to know the doseresponse effect for humans. These are much the most difficult problems; but indications of exposures have been given by industry spokesmen ar.d eorae refinement of these must be possible. With these available, the human mortality data nay bo susceptible to analysis. In addition, we need a detailed development of a dose-response relationship for rats, froa Maltoni's data. At best this relationship may be cohesive with and supportive of any tenuous relation we develop froa human information: at worst we may have to use it alone, possibly with arbitrary factors applied, since the crude data does seen to suggest that rats say be more sensitive than man to vinyl chloride. A dose-response relationship is essential for the last correction which requires the calculation of the risk of getting angiosarcoma in 1935 after exposure to only a few ppra of vinyl chloride. This may be difficult, but we have a duty to the people in the industry' to atteapt it. Perhaps we do not have to be overprecice, for if we are correct in believing our new standards to give a large margin of safety, the calculation, of extremely low risk at these exposures may not be too sensitive to errors in the extrapolation. All this then needs to be done. What is being done? Within TCI, ay colleagues Dr V.'illiarr.son und Dr Paddle are working on the problem, but it is difficult within one company to achieve everything, for the data available to us in ICI may not be representative of the world situation. Nevertheless I believe they will be able to publish some preliminary observations shortly, end I know they would welcome comment, suggestions, or involvement with them, on the subject. The word "involvement" brings me back to ray subject of "interactions". Vhcn the task - of devising safe operations - was clear, many institutions in Europe interacted well and achieved much. I've tried to chow uhat much remains to be done: so let interaction, co-operation and contribution flourish still. As another of my colleagues, Dr John Stafford, has put it "the sooner we address and apply ourselves ... unreservedly to ... the tank the sooner wc shall ha'-e really well-founded data to satisfy ourselves, our neighbours, customers, critics etc that the VCM health problem has not only boon satisfactorily contained but finally solved." AWI1/JJG September 1976 AP00048822 B CD tO O ci) n c/) Jg w < u v" M N lO v* v- 04 CO PO CM CM rOj<NJ rj- T- * I C^l I I *- vCL.) O tj x- CO to ro .tr: o .O a. i * & i n,firttor'Oicr(Or-NM'i^in5n-K>ao<-cMfOTfin '(JJ"icflo,oTji,c,<n3,c'DtfC'\TDMCn'icrntia.'i)CwTiainiDicnnincnirc)nirc)niocninOiToOtoTicDiCtDo cidnccnd r-- -- -- 1- -- t- i-> t~ r- -- t*" -- t-- r* -- v-- v" i" r- v~ r" v-- 1968 AP00048823 wc t L : <.,/ W 'lv ~r V f. u tv t-Ui ': ; no f'r'Pi "r Ch.- n.i-'j,/,/, ,V- v' - A to PV I! V-P jr defects "5 r- i" -3 Jly!!.`KSl'KIlOS r TeJogrophStaff r.' jiti; Uw A survej'l>v The I'clegraph indicates t o iri-*t Th* Tebyrepb survey cn possible oileels ol UiC use i)l L? Vvii:n1^vi rc!l'uride in luo a. ca if,i b. e,tween .th. e occurK-.,U. ou o.f purer.*,, sc i'.f- ..~.w.A.,*aCi.t',,rr--;*>i3ni <1 v.'.MSt'S '-I'.tV tVlE . I;.bn'Vri7. .,l.r,V* 8 Kinesvitle in JS73 ;mw! the r.bnortnail.v !: r ,v.u of birth effects l in tue TB^' J t.h.e...a..re..a...f.o.r...H..u4lt veer , jj area v.r.s <>or-.e using sci-mtm*: *** polling tccluilques. The Ohio Department of Health rcuorleri in August that it was investigatin'-; tcp:.; is dut three nocthavfern Oluo cf,:ruwti;iit!es, irclu-Jir..'. l'ainesvil'.e, twcl crub-lc the stiUfv.idc average c>f birth tic-fccts for 1573. The reports inched t!'.v Uofect rjr* to >;.'c cf viuyi ciiloricisi in Industrie! plants in Avyii Hshe, Ashtabula, and Pai/icsyille. Each certificate cf birth at the Pr.-r.cjviUt; Cily Health IlJcper^mrnt is mrmkervri consecutively. The cer tificates also show whether th* baby was born with nny Painesville fad 820 births in l?J with 23 boro with birth Vdnd of birth defect and iha defects or congenital rad 'far mat ions. This r-rce the city a rsfe of, name and address of the 27.<''efi'Ctsper thoumr.ri at compared with a statewide average parents. cMl.2 defects per Husucntl fciilkr-. Honoris from the AI-T^CIO Industrial Union Commit fee hud indicate:! tint tha defeats in `acvrtal communities miybt be related to the use of the chemical, used to rar.kc polyvinyl chloride, the most common form of plastic. Each birth certificate that noted a baby born with a defect \st.s made part oi the sample called the "ex Tta Telegraph survey found that cl .he 3 children torn in JP73 with riefects^V^r^ivjii.fj^rorT at either L'nlrnyaJ or Kobinfech, U\o two n.vu picats ;ha; n?e vinyl chloride. I:i the control group of parents c! children bom RorinaUy that year, one also worked at a vinyl chloride plant prior to his child's birth. perimental" group. The nr.rne and address of the 23 children born with defects in 5073 was taken es the basis for pollmj. To select a `'control'' group, or group Chat accurately Similarities also existed between pveups of parents v.ho uA-hcd in CsieiTdct! pt.-uts v.-l-.cre vinyl chloride was not tied, and r'ro Uriv/ecn tjrov.ps r: parents who worked in plants or carccts in v.hicii volatile chemicals were not used at ail. represented the entire population of babies b'-rr. in Piii::esv/!l'2 j;i ]?73. a nvidoiw se!ccfio:i process was used. A number between one and 33 No correlation could lv? found between the type of defect in the child, or rcaidviwo of the parent, and oca:paticn. A erftts bibul.'iUo'.i r.f tUov vs-rfebbs produc-rd cwly prr.uvr.s. Hyolint* mcmbrcr.c curoasc f r. d'sc.'^e that prevents air from cnb.rjf,;- tlu tlo:;l:/.rtv.ni in the i'imj.s) was f.he most ccmmo/i detect.a:i'i Paines.!!>, M.ahsocx, and Ntauiran wore the corumwiilivs sviJi LVj greups. cv/iccn[rctio;i c: birtiis in both was selected at random, awl Che certificate with that number mr.de part o: the central sarnyfe. Each sub sequent 3:ih certificate aitor that was also marie part of thi sample U maV.c a control sample of 25, approximately the same minibcr as iu Ihe experinicjit al sample. L'ecausc liw first ccrUMcv.to was cluwi.*) at rendom, each birth heel .ri cnu.:d chance of being included in the coi.li-ol S3m[i!o. In three cases, the 35th subsequent certificate* could not bt included in the r<ri control sample, cither because it v;n.\ one irwludju In Ilia c.vpeiii'K'n.tiil r.-mplv, w* Ivcnu.-O ti 'hy uus ;v.U-'..ted ami (i:-: iehtitity of i:*-. [ m er.t.s cotihl nrl b? cv'tvrmiiwil. In 'each ci U-- U.rvc '.hr jir.vt teih.'i-'.A'* wes U.V.on, C.mJ [h-; ,'iiLftU'Si tf sv.h- | sequent u*sp'.mlvn`..'. l.;);en b.n.ru u.j'Ui the orlitin.il j SClvH'ai in l>'th i;,by (i'ti'ph`'iiu mi;; ''-in I'nvi. irt.pi'UuMit ti'/i i'i-v "mi'i f.;cn ncltvtffl tn p-'ct"' i ate it. an occ'ipuik'titil s>. \.y.." h i.-- ycf;pu:r.!vnts wore U*..y:i .'r.knd aiiu occupation ot hull*, parents, the company t!V*y uxi ki.*ct for, atiJ U.e !v;t ;Ut of lime with tlr.tccmpany. V.'imn cUhcr parent h-tai v,v;!:c'i fjr his or her f.rosent cinnlt-yLT for loss limn five yc:-'r., th? rcsponriuuts were tl-.o name of the former employer and the riatca worhc.l iu an attempt to ife'.tTiriou the employer jii.-.t prior to ilu lime tl'.e baby vpr. born. If the respondents could not be reached by phone, cither because Ihc-re war. no current listing or bocsusc tlurc was no answer alter n-jwtufej attc-mptr, the cccupattcn c: the respondent was cicfeTniir.eii by luri.ig various dirccterie; for 1372 and 1573. Jn two case? In Ihci e.'rpcrhner.lal and 12 cases it: the control f.raup, the respondents could not be reached and had no listing in the directories, and their names were discard-d from the sample. The answers from the respondents were Vnyu piacr.-d fnto feur categories. . , . : ' I j . 1 The first category included those who har! v.-othed ?.t either Unitoyai cr Itc-I.lntcch just prior to lire birth t.l their c* lid in JC73. ! 1 ' The second category in- \ eluded those who hci weri-ti-d ; et eithur n nfent in ..!lie'! ?V<r or other volatile cirern.cal was used, or worked as a : laboratory technician where . the weritur wa? in c\ ;;ioot with . chemicals of vuriov.i nab.rc . tlu*ou-,liout the worivi:;--. d-*v. i I The liiird category ivn used : for rr.i.poni'.eTitr. v.l-.e v.ttV.vu m ' phials or j lir.t Icul no co:>;wcUr;nu'i!h th? VCnr i'VC ' ir.t'uj.lry or had no contact ; with ciicrnicals. j The fourth cnlci'e:y wes itsr-d for U.o:c who :nv the (nlrjviouvr f.'J<V.f;icJ.**it ir>- fOMinM..>:i v. i:h v. to (hat i c: por.l.Tit in any (" tho fii>l thru? eut.n/.uri.'.i. Tka rc;::.iH ; of the -i :.v.ac;:: Ic feuvi-l in llw, t.dib::.. ] . . , ` AP00048824 fc':SS; infernatior, j! pigsties news hidnietj Britain's `OSHA' has second thoughts about VCM An article in a recent issue of the British Medical lournaf suggests that vinyl chloride monomer may not be as serious a hazard as was formerly supposed. In that publication (Oct. 7, 1977), Or. Peler Baxter and three other doctors who are affiliated with the Health 6 Safely Executive {a British govern ment agency similar to our OSKAV reviewed the preliminary report by the agency on the incidence of angio sarcoma (liver cancer) in Great Britain. Specifically the report looked for any correlation between incidence of the disease among workers and in the general public around factories where PVC resin is manufactured or pro cessed. Reviewing health records for the 10-yr period of 1963-73. the study states that of the 47 cases of liver cancer reported, in only 14 instances was the diagnosis confirmed. Further, of those 14 cases, only one could be "confidently associated" with expo sure to VCM. In that instance, the worker had probably been exposed to VCM concentrations exceeding 200 ppm in air for more than 20 years. The VCM exposure standard in Britain is 10 ppm averaged for an 8-hr day. Turning to the statistics for the general population, living near PVCusing plants, the study found one confirmed case of angiosarcoma, a man who lived within half a mile of Such a plant for 6 years before his death. However, no correlation could be found between the incidence of the disease in the general population and `he location of PVC operations. The report also failed to find any cases of the disease that could be attributed to ingesting VCM from foods contained in PVC packaging materials. Based on that 10 year period, the article's authors concluded that the incidence of this type of cancer in Great Britain appears to be considera bly less than 10 cases annually in a population of 50 million and that only one case of the disease diagnosed during that entire 10-yr period could be definitely associated with VCM exposure. The authors, however, did not dismiss the possibility that angiosarcoma could be caused by low-level exposure to VCM and endorsed a continuing monitoring of the situation. Commenting on the study, a spokesman far the Employment Medical Advisory Service, the parent This r.h-V I J.' if) ) f'Oiyi'ttn :cnc /vU' w.is recently c>tr:/a<:U on a tc'O nun (o' t d in ) ixttndcr in ,1 tn.it run .11 tf'o outlier's nt.in t bi'toro stuntnent to .1 pipe producer re -urepo. Designed ami Oui/I fry L u>g> lUndur.1 S.p A. thisto A>si:to. tuiy. wo oxt/udor 1M I raiod output of about IfbO 10'hr *ncl ettn produce pipe 0/ up to 55 in. din. Organization of the Health A Safety Executive, stated: "The findings give us grounds for hope that the chemical wifi turn out to be less of a cancer risk than v/hen the American" findings wore announced." U.K. plastics production posted gains in *77 Though final figures for the year are not yet available, plastics production figures for the first 6 months of 1977 indicated that the year may end up about 6% higher than 1976. Eased on the first half of the year, 1977 plastics production totalled 1.356 million metric tons (about 3.56 billion lb), This represents an annual rate Of about 2.7 million tons, compared to 2.56 million tons in 1976. Considering the lethargic state of the (1000 metric tons) Alkyds Polyesters Aminos Phenolics Epoxides Polyurethanes Ocher thermoset* Total 444.3 72,4 34.1 92.0 29.8 , 11.2 38.4 166.9 Acrylics Polyethylene Polyethylene PVC 33.3 264.5 133.3 208.1 Other vinyl* Polystyrene (crystal) Polystyrene (impact) Polystyrene (expanded) Other styrenes ASS Polyemides Other thermoplastics Total 651.6 5.7 34.2 53.9 29.4 5.3 16.6 16.4 14.7 . Total 1296.4 British economy, this performance is viewed as reasonably satisfactory. Looking at specific resins, there was no major growth area. Both polypropylene and polyethylene ran ahead of '76. though PVC production remained level, With the exception of polypropylene, there was no major shift in the level of exports or imports. PP, however, was up about 34% on on annualized basis over the 71.000 metric tons shipped in 1976. Imports of pp were up almost as much, about 20%. Thu flCCorip4in\inij tnhfr* shown the U.K. production by resin lor tho first half of 1977. 12 FotiruAry - ~.i>< < | | ; < : * | [ I j 1 j * ; j L ** ' ?* f. r <: : l' Z. tic*l-` rr I' o ti. AP00048825