Document Eqqm8B3XeEdaxG716v16Rby8V

IN THE UNITED STATES DISTRICT COURT FOR THE NORTHERN DISTRICT OF OHIO WESTERN DIVISION 1 2 Mary A.; Dendinger, et al.. 3 4 v. Plaintiffs, Case No. C87-7117 :f 5 Chrysler Plastic Products Corp.~ et al., 6 Defendants. 7 8C 8 10 11 12 13 DEPOSITION upon oral examination of 14 PROFESSOR SIR RICHARD DOLL taken on behalf of the 15 Defendants before Christine Mary Armstrong, Accredited A 16 Court Reporter, commencing at 11am at Green College, 17 Oxford, England on the 26th day of July, 1968. 18 19 20 21 22 23 24 25 UCC 072946 2 1I 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 APPEARANCES For the Plaintiffs: KIRK J BELLI BOVI Esq. of Murray a Murray Co. L.P.A. 300 Central Avenue, ... Sandusky, Ohio 44070 For the Defendants: ROBERT A BUNDA Esq. of Fuller 6 Henry, Attorneys at Law, One Seagate, 17th Floor, P O Box 2088, Toledo, Ohio 43603-2088 UCC 072947 3 INDEX 1 Page 2 PROFESSOR SIR RICHARD DOLL, sworn 3 ^Examined by MR BUNDA 7 4 Cross-examined by MR DELLI BOVI 51 Re-dlrect examination by MR BUNDA 143 5 Further cross-examined by MR DELLI BOVI 148 Further redirect examination by MR BUNDA 149 6 7 8 9 10 11 12 13 14 No. EXHIBITS Description Page 15 Defendant 1 16 Defendant 2 17 18 Curriculum vitae Review by Dr. Doll vpublished 1988 Marked for identificat ion prior to the. commencement of the deposition 19 Plaintiffs' exhibits were marked by counsel and not released to the reporter. 20 21 Plaintiffd1 exhibits subsequently supplied and attached to transcript. 22 23 24 25 UCC 072948 4 1 MR BUNDA: My name is Robert Bunda. I am attorney for 2 the Defendants in the case of Mary A. Dendinger et al v. 3 Chrysler Plastic Products Corporation et al, a case arising 4 in the United States District Court for the Northern Distric 5 of Ohio, Western Division. 6 MR DELLI BOVI; I am Kirk Delli Bovi, representing the 7 Plaintiffs, Mary A. Dendinger and Etta Wallace. 8 MR BUNDA: (To the Reporter) Would you swear the 9 witness? 10 PROFESSOR SIR RICHARD DOLL, having been duly sworn, 11 testified and gave evidence as follows: 12 MR DELLI BOVI: Before we begin Dr Doll's testimony, 13 I would like to make an objection for the purposes of the 14 record to both the place and the time of the taking of 15 Dr Doll's deposition. The taking of Dr Doll's testimony 16 in Oxford, England, has imposed a great financial burden 17 on the Plaintiffs in this case. There has been no showing 18 by the Defendants that Dr Doll could not have been produced 19 in the United States to give testimony which would have been 20 far more cost-saving in terms of time and money both for 21 the Plaintiffs and their counsel. Second, I want to 22 register an objection to the time of the deposition. On 23 July 19 I corresponded with you and requested that I be 24 provided on July 25th with all the articles and other infor 25 mation upon which Dr Doll will base his expert opinions Tennyson & Compeny - Court Reporters London, England 0114402424164 UCC 072949 5 1 today. Because of plane mis-connections in Pittsburg, 2 instead of arriving in London at 6.30 yesterday Doming, 3 I arrived in London at 8.50 yesterday afternoon. Yesterday 4 morning, I had my secretary contact you here in Oxford and 5 request that the documents that I had requested from you 6 on July 19 be made available at my hotel so that I could 7 review them upon my arrival. At my hotel, which incidental! 8 is located within a mile of Dr Doll's office and your hotel 9 room here in Oxford, upon arriving in at the hotel, none 10 of the documents were there. I immediately contacted you, 11 you indicated that the documents could not and would not 12 be made available to me until 9 o'clock this morning. When 13 1 arrived here at 9 o'clock this morning 1 did receive some 14 of the documents that Dr Doll is going to be relying on and 15 some of the documents I requested that he had authored and 16 were in his curriculum vitae. However, I did not receive i 17 this morning a number of unpublished papers that are listed 1 18 V in the references to Dr Doll's report and accordingly, I 19 have not had an opportunity to review those. 1 have not 20 had an opportunity to thoroughly review the hundreds of 21 pages of documents first presented to me at 9 o'clock this 22 morning and accordingly we object to the time of the taking 23 of Dr Doll's deposition this morning. 24 MR BUNDAs For the record in response, my understanding 25 is that you arrived in Oxford at midnight last night. The Tennyson & Company - Court Reporters London. England 01144-12424164 UCC 072950 6 1 information was of waiting for you all day on the 25th. 2 The unpublished documents which serve as the basis for 3 Dr Doll's review were requested by him to remain in his 4 office and under his control, to which request I acceded 5 and I so informed your secretary when she called. We also 6 made available to you this morning* the 26th July* at appro i- 7 mately 10 o'clock, an opportunity to review those documents. 8 You were also provided with an opportunity to take a 9 discovery deposition of Dr Doll which request you declined 10 - - let me finish. 1 have asked Dr Doll to provide you wit! 11 those articles which you requested from me which had been 12 listed in his curriculum vitae, many of which are published. 13 He brought with him those he had in his possession, this 14 morning, which documents were made available to you between 15 10 and 11 o'clock. 16 THE WITNESS: May I interject. All the ones I was 17 asked to produce were produced, with the exception of one i V I 18 Canadian article which I have used- in my evidence which has 19 been in the public domain for several years. 20 MR BUNDA: Which were you not produced? 21 MR DELL1 BOVI: The ones I listed as references in 22 Dr Doll's report are the following unpublished articles: 23 Bar, 1981; Bennett, 1986; Barnes, 1987; Downes, 1977, 24 and Equitable Environmental Health, 1978----25 MR BUNDA: For the record, to my knowledge -those were Tennyson & Company - Court Reporters London, Englend 01144*12424164 UCC 072951 7 1 never requested. The request 1 understand you made was for 2 the four primary articles which serve as the basis for his 3 opinion. Three of those four were provided and the fourth, 4 as DrtDoll has indicated, is in the public domain as having 5 been published. 6 MR DELLI BOVI: For the purposes of the record and*we 7 can mark this as Plaintiffs Exhibit 1, is a copy of my 8 correspondence to you dated July 19, 1988 in which I 9 requested: "All of the articles and other information upon 10 which Dr Doll will base his expert opinions." 11 THE WITNESS: For the record, I do not think I shall 12 base any opinion on any of the articles to which Mr Delli 13 Bovi referred. 14 EXAMINATION 15 BY MR BUNDA: 16 Q Dr Doll, would you please state your name and age, for j 17 the record? .v j 18 A My name is Richard Doll. I was born in 1912 so I am I 19 7520 Q Doctor, what is your profession? 21 A I am a medical practitioner and have, for some years 22 now, been a professional research worker. 1 then became a 23 university professor and Z am now working on cancer research in 24 an honourary capacity. 25 Q Doctor, where are you employed presently? Tennyson & Company - Court Reporters London, England 01144-12424164 UCC 072952 8 1 A In the Radcliffe Infirmary In the Gibson laboratory 2 for the Imperial Cancer Research Fund. 3 Q Where is physically that Cancer Research fund located? 4 A The Head Office is in London but they have a number 5 of independent units and at the moment I am an honourary member 6 of their unit in Oxford, acting temporarily as the Director of 7 that unit - - as the recent Director has just resigned and the 8 new Director cannot yet take up his post. 9 Q That is Oxford, England? 10 A Oxford, England, yes. 11 Q You Indicated you were a medical practitioner. Is that 12 the same as a medical doctor? 13 A Yes. 14 Q Where did you get your medical degree? 15 A In the University of London, St. Thomas's Hospital. 16 Q In what year? 17 A I got the degree in 1937. 18 Q Have you received a Doctor of Science degree? 19 A Yes. 20 Q When was that? 21 A The first one I got from the University of London, I 22 cannot remember precisely, late 1950s, early 1960s, I am not sure 23 Q Let me hand you Defendants Exhibit 1. (Document handed 24 to the witness) Could you identify that for us, please? 25 A D.Sc., 1958. Tennyson & Company Court Reporters London, England 01144*12424164 VCC 072953 9 1 Q Yes, the document itself, is that your curriculum vitae ? 2 A Yes. 3 Q It also has attached to it a list of your publications, 4 is that correct? 5 A Yes, 6 Q Have you received subsequent degrees since that time? 7 A I have received several honourary degrees, yes. 8 HR DELLI BOVIs For the purposes of the record, and 9 I believe there is a local court rule that pertains to this, 10 we will stipulate to the qualifications of Dr Doll. It is 11 my understanding that you have in fact offered his curricu 12 lum vitae into evidence and we will stipulate as to his 13 qualifications also to render expert opinions in the areas 14 in which you choose to enquire. 15 BY MR BUNDA: 16 Q There are certain items listed in the curriculum vitae 17 not familiar to an American jury so I would like to go through j 18 your qualifications, if IAcculd? j 19 A Yes, sir. 20 Q What were the honourary degrees? 21 A 1 was given an honourary D.Sc. in the Universities of 22 Newcastle, Belfast, Reading, England. Newfoundland in Canada, 23 the degree in Tasmania of Doctor of Medicine and honourary degree s 24 of science in two universities in the United States, the New YorV 25 State University and Harvard. Tennyson & Company Court Reporters London, England 01144*12424164 UCC 072954 ------------------------------------------------------------------------------ nr- 1 Q Those last two are not listed cn your curriculum vitae 2 They are new awards? . 3 A No, I was awarded those this year. 4 Q What professional awards have you received? 5 A It is difficult to remember. 6 Q You can refer to your curriculum vitae. 7 A May I? 8 Q Yes. 9 A Are you referring to prizes and that sort of award for 10 cancer research and that sort of thing? 11 Q No, sir. If I could see your curriculum vitae for a 12 second - (document handed to counsel) - you have listed on ther 13 professional awards immediately beneath Honorary Degrees and 14 those contain several series of initials and I would like to knov 15 what those are. (Document handed to the witness) 16 A These are either examinations I have taken to qualify 17 me to be a consultant in medicine, that is the Fellowship of the ! V ) 18 Royal College of Physicians, but I have some Honourary Fellowships. 19 Fellow of the Royal College of Practitioners and Fellowship of 20 the Faculty of Community Medicine; Fellowship of the Faculty of 21 Occupational Medicine of the Royal College of Physicians. I also 22 have the Fellowship of our Royal Society in England which is, 23 I suppose, the nearest equivalent of the Acadamy of Sciences in 24 the States. 25 Q Below that on your listing of Honours, you have Kt Tennyson & Company Court Reporters London, England 01144*12424164 UCC 072955 11 1 listed. What is that? 2 A Oh, that is an English peculiarity. It stands for 3 Knight. It is an old custom to award this title to some people 4 in this country, twice a year on the Queen's Birthday and also 5 on the 1st of the year. 6 Q And you have been awarded that honour, air? 7 A Yes. B Q I have heard you referred to as Sir Richard Doll. Is 9 that as a result of the Knighthood, sir? 10 A Yes. 11 Q How do your colleagues refer to you, as Dr Doll or 12 Sir Richard? 13 A If they do not know me very well, as Sir Richard. If 14 they know me well, just as Richard. 15 Q Sir, what is the purpose of the knighthood. Do you 16 know why you were knighted? 17 A No, they do not tell you, it just says "For public ? v j 18 services", and I presume this was for the results of our research 19 Q Which research? 20 A Primarily, I imagine, our research into the causes of 21 lung cancer, particularly the effects of smoking, but also into 22 the effects of ionizing radiation and their relation to productic n 23 of cancer and other studies of national concern like the effects 24 of oral contraceptives and the effect of asbestos. These were 25 all early studies which I imagine influenced whoever St was that Tennyson & Company Court Reporters London, England 01144-12424164 UCC 072956 12 1 made the recommendation that I should be given this honour. 2 Q Now, sir, you also have listed an award, the OBE. What 3 do those initials stand for? 4 A OrSer of the British Empire. 5 Q What is that? 6 A That is a decoration which is given by the Queen on 7 the Prime Minister's recommendation. I do know what this was 8 for. It was for our early work on demonstrating the relationship 9 between ionizing radiations and production of leukemia and the 10 first estimate of the amount of leukemia that might be produced 11 by a given dose of radiation. 12 Q Did you serve in the World War II in Europe and the 13 Middle East? 14 A Yes. 15 Q Sir, if you would for the jury, could you outline some 16 of the medical posts which you have held leading up to your present 17 position? -v '1 18 A Yes. I started as an internal physician and, of course, 19 the war came shortly after I qualified. I was first of all a 20 medical officer to a battalion. Then I became a medical specia 21 list in a hospital but I immediately after the war ended, I 22 started research and I have been doing research ever since, 23 employed by the Medical Research Council until I was appointed 24 to be Regius Professor of Medicine in Oxford in 1969 when I 25 continued with the research but also had some acamedic and Tennyson A Compsny - Court Reporters London. Englsnd 01144-12424164 UCC 072957 13 1 administrative responsibilities. For the first twenty years or 2 so after the war I also continued with some clinical medicine, 3 with the care of patients suffering from gastrointestinal disease: 4 because X yas doing, at that time, clinical research into the 5 methods of benefits of different sorts of treatment for gastric 6 and duodenal ulcers, but I have not done any clinical work since 7 1969. 8 Q Sir Richard, you have also listed on your curriculum 9 vitae that you are a warden of Green College. What is that? 10 A Well, that title, warden, means the Head of the College 11 and we have some 35 colleges in Oxford. When I retired from the 12 professorship 1 was made Head of this new college. Green College, 13 which has a special interest in clinical medicine. 14 Q Could I see your curriculum vitae, please? (Document 15 handed to counsel and returned to the witness) Can you confirm 16 for the jury, sir, that you have been honoured with the following 17 awards: The William Julius Mickle Fellow Award from the 18 University of London in 1955? | 1 i j 19 A Yes. 20 Q The David Anderson Berry Prize from the Royal Society 21 of Edinburgh in 1958? 22 A Yes. 23 Q The Bisset Hawkins Medal from the Royal College of 24 Physicians in 1952? 25 A Yes. Tennyson & Company - Court Reporters London. England 01144-12424164 UCC 072958 14 1 Q The United Nations Award for Cancer Research in 1962? 2 A Yes. 3 MR DELLI BOVI: Excuse me for interrupting. This time 4 I would*.like to renew our objection to at this point 5 reading from Dr Doll's curriculum vitae. That document 6 presumably will be in evidence. At this point it speaks 7 for itself and again 1 believe there is a local rule that 8 governs qualifying the witness. 9 MR BUNDA: Again I believe that the Awards need 10 explanation. 11 MR DELLI BOVI: May we show a continuing objection? 12 MR BUNDA: Yes. 13 BY MR BUNDA: 14 Q The Awards 1 mentioned, are they for specific work or 15 is that a general award for the work you have done until that 16 time? 17 A They usually referred to specific items of work, 18 principally the effects of smoking, the effects of ionizing 19 radiation and the effects of asbestos. 20 Q The Gairdner Award, Toronto, 1970. 21 A Yes. 22 Q The Buchanan Medal of the Royal Society in 1972. Did 23 you receive that Award? 24 A Yes. 25 Q What was that for? Tennyson & Company Court Reporters London, England 01144*12424164 UCC 072959 15] 1 A For epidemiological work. 2 Q In 1973, did you receive the Nuffield Medal? 3 A Which, I am sorry? 4 Q Nuffield Medal? 5 A There must be a misprint. Oh, Nuffield. I cannot 6 remember what that was for. 7 Q You have had so many. The Presidential Award, New 8 York Academy of Sciences in 1974. Do you recall that you 9 received that? 10 A Yes, for general epidemiological research. 11 Q This is a French word now, Prix Griffuel, in Paris in 12 1975. 13 A For cancer research. 14 Q John Snow Award, Epidemiological Section, American 15 Public Health Association in 1976. Did you receive that? 16 A Yes. 17 Q What was that for? V 18 A Epidemiological research in general. 19 Q And the Gold Medal, Royal Institute of Public Health 20 in 1977, did you receive that? 21 A Yes. 22 Q What was that for? 23 A I cannot remember. 24 Q The Charles S. Mott Prize for Cancer Research, in New 25 York in 1979. Did you receive that? Tennyson & Company - Court Reporters London, England 01144-12424164 UCC 072960 16 1 A Yes. 2 Q That was fpr cancer research? 3 A Yes# that specifically mentioned the work on smoking, 4 ionizing radiation and asbestos. 6 Q And you received the Gold Medal of the British Medical 6 Association in 1983? 7 A Yes. 8 Q Do you recall what that was for? 9 A General medical research and helping other people in 10 their research, I think. 11 Q The Wilhelm Conrad Rontegen Prize. You received that 12 in Rome in 1984? 13 A Yes. 14 Q What was that for? 15 A I do not know what was specified for that. 16 Q There was another that appears to be a German or I 17 Austrian prize awarded in Hannover in 1985. The Johann-Georg- 1 18 Zitnmermann Preise? a- i 19 A Yes, for cancer research. 20 Q And the Founders* Award from the Chemical Industry 21 Institute of Toxicology in 1986, do you recall that? 22 A I expect that was for the book I wrote with Mr Peto 23 on the causes of cancer. 24 Q The Royal Medal from the Royal Society in 1986, Do 25 you recall that? Tennyson & Company - Court Reporters London, England 01144-12424164 UCC 072961 17 1 A Yes, that was for epidemiological research in general. 2 Q Which Royal Society? 3 A The British Royal Society which I think is the equiva 4 lent of the American Academy of Sciences insofar as there is any 5 equivament. 6 Q I would ask you also to review the committees on which 7 you have served or which you are presently serving and indicate 8 whether those listings are accurate. (Pause) 9 A Yes, they are accurate. 10 Q Sir Richard, attached to your curriculum vitae is a 11 list of publications. Is that right? 12 A Yes. 13 Q Is that a list of the articles which you had published 14 in your career? 15 A Yes. 16 Q Are there additions to that list? j| 17 A None of any importance, no. i i 18 Q There is at least one article not listed on there , a 19 recent publication of yours regarding the effects of exposure 20 to vinyl chloride? 21 A Yes, that only appeared in April this year and I forgot 22 1 had not brought the list up to date. 23 Q Well, I remembered for you. Could you identify Exhibit 24 2 for me please? (Document handed to the witness) 25 A Yes, that is the article. Tennyaon & Company * Court Reporter* London, England 01144*12424164 ucc 072962 16 1 Q Doctor, of your 345 articles approximately, what per 2 centage of these deal with cancer? 3 A Oh, at a guess I would say about three-quarters. 4 Q What are some of the carcinogens you have studied in 5 your career? 6 A Apart from tobacco smoke, ionizing radiation and 7 asbestos, nickel compounds, chrome compounds, mustard gas, vinyl 8 chloride - - oh dear. Combustion of fossil fuels, urban smoke 9 and the fuels from combustion of coal gas retort houses. I 10 cannot remember if there are any more. 11 Q This body of literature you have produced, do these 12 articles deal with the causes of cancer? 13 A Yes, mostly. 14 Q And has the Office of Technology Assessment of the 15 United States Congress ever asked you to publish any study? 16 A Yes, my colleague Richard Peto and I were asked to 17 write a report on the causes of cancer in the United States and < i 18 of the proportion that might be avoidable by different means. 19 We were asked to do that several years ago and that was the 20 reason we wrote our book on the causes of cancer. 21 Q Do you recall from that study, sir, what percentage 22 of cancers approximately can be attributed to occupational 23 sources? 24 A Yes, we made an estimate that approximately 4 per cent 25 might be. It is very difficult to give a precise figure but that Tennyson A Company - Court Reporters London, England 01144*12424164 UCC 072963 19 1 seems a reasonable estimate of the proportion of fatal cancers. 2 Q Doctor, I would now like to discuss with you the field 3 of epidemiology. Sir Richard, are you an epidemiologist? 4 A Yee 5 Q How would you describe your role in the development 6 of the modern field of epidemiology as it relates to known 7 infections, diseases? 8 A 1 was very fortunate when I came out of the Army after 9 the war. I worked for the Medical Research Council with Doctor 10 Avery Jones on the causes of gastric and duodenal ulcers and the 11 occupational causes in particular and in the course of doing that, 12 I met Professor Bradford Hill at the London School of Hygiene 13 and he asked me to work for him and from 1948 until he retired 14 in 1961, I worked with him and he really was the man, the father 15 of modern epidemiology. I think 1 can say in the world. Up 16 until then epidemiology had been principally a science studying I 17 the causes of infectious diseases and as infectious diseases v 18 became controlled , it became of less general interest, but > ! 19 since that period, the period of the war, the techniques of 20 epidemiology have been applied to known infectious diseases such 21 as peptic ulcers, coronary heart disease, as well as cancer and 22 Professor Bradford Hill was really the person who developed the 23 techniques for deciding whether or not a particular factor was 24 a cause of a known infectious disease by epidemiological means. 25 I was fortunate enough to work with him at that time end so I Tennyson & Company Court Reporters London, England 01144*12424164 UCC 072964 20 1 helped him develop some of these techniques in the very early 2 days of the subject. 3 Q Doctor, can you explain for our jury what epidemiology 4 is? - 5 A Yes. Epidemiology is a study on variation in the 6 instance of disease in different groups of human beings. By 7 studying the way the incidence varies in different environments 8 and with people who behave in different ways, we can discover 9 what are the causes of the diseases from which they suffer. 10 Q Doctor, are you familiar with the field of medicine 11 called occupational medicine? 12 A Yes. 13 Q How does the work that an epidemiologist such as your 14 self does, differ from what an occupational physician does? 15 A An occupational physician will have clinical care of 16 people working in the industry, but the greater part of his 17 research will be epidemiological research. The majority of 18 occupational health researchers nowadays use epidemiological 19 techniques so it is very much a part of epidemiology. 20 Q How long have you been doing work in the field of 21 epidemiology? 22 A Since 1946. 23 Q And in the area of epidemiology of cancer causation? 24 A Since 1948. 25 Q Have you taught epidemiology? Tannyson & Company - Court Reporters London, England 01144-12424184 UCC 072965 21 1 A Yes. 2 Q When and where? 3 A Mostly post graduate teaching which 1 have done ever 4 since 1949.or 1950. Once I knew something about the subject. 5 A little bit of under graduate teaching in Oxford and elsewhere, 6 but mostly post graduate teaching. 7 Q Where did this occur? 8 A All over the world really. At the London School of 9 Hygiene in England, in Oxford University, but in universities # 10 all over England and in many parts of the world as well. 11 Q Have you consulted with researchers in epidemiology 12 from different countries? 13 A Yes. 14 Q I would like you to explain to the jury a few terms 15 which they may have already encountered in this trial or may 16 encounter later. What is a case report? 1 17 A A case report is an account of the development of the i V I 18 disease in an individual. It is a clinical description of a 19 disease in an individual. 20 Q Is it necessarily concerned with determining the cause 21 of the disease in the individual? 22 A Well, it can help to suggest causes if a number of 23 case reports all point to the same type of behaviour in the 24 Individual or (he same type of exposure and, in very rare cases, 25 even one case reported in the light of knowledge generally, can Tennyson & Company - Court Reporters London, England 01144-12424164 UCC 072966 22 1 lead to the discovery of a cause, but this is quite exceptional 2 if the type of disease produced is a disease vhich is extremely 3 rare normally. I will give you an example in which two cases, 4 two case reports led to a discovery of a cause when a GP in 5 South Wales had two patients with cancer of the ethmoid sinus 6 of the nose present in his practice* both of whom were working 7 in the same plant and he knew from his teaching as a student that 6 it was unlikely he would see one such case in the whole of his 9 practising life and he was able to draw the conclusion that 10 almost certainly their cancer was due to their work. 11 Q Generally, does medical science use case reports to 12 describe cause and effect in an occupational sense? 13 A Oh no. They are of very little value in relation to 14 common diseases. 15 Q Is a case report the same as an epidemiologic study? 16 A No, it is quite different. 17 Q What is an epidemiologic study. How do you go about V 18 doing it? i i 19 A Well, an epidemiologic study requires two things. It 20 requires the determination of the number of cases of a particular 21 disease or condition and also the determination of the population 22 in whom those diseases occurred because we very seldom have a 23 situation in medicine in which a person is exposed to a cause 24 and automatically gets the disease. 100 per cent exposed get 25 the disease. When that happens it is very easy to discover the Tennyson & Company - Court Reporters London, England 01144-12424164 UCC 072967 23 | 1 cause. For most of the chronic diseases, exposure to a cause 2 only gives rise to a risk. 1 in 100 people may get the disease. 3 1 in 1,000, 1 in 10,000 even and epidemiology requires con 4 structing the. relationship between the development of the 5 disease and the population of people who were exposed to the 6 cause of that disease. 7 Q I have heard the term cohort used. What is that? 8 A Cohort is a technical term which was Introduced to 9 describe a group of people who are defined and who are then 10 followed forward over a period of time to see what happens to 11 them. It was introduced in the first place to describe a group 12 of people born in a certain period. You would speak of the cohoi t 13 born before the First World War or the cohort born in the 1930s. 14 That would define a group of people and you could see how their 15 experience, their medical experience differed from those born 16 before or afterwards, but you commonly now use it to describe 17 all the employees of a particular factory. That would be a i I 18 cohort. I have been studying a cohort of doctors who gave me 19 their smoking habits in 1951 and I have been following them ever 20 since as a matter of fact, or rather the survivors. 21 Q You observe them over time to determine what is 22 happening to them? 23 A Find out if they are still alive at a given date later. 24 If they are not, if you cannot find out if they are alive, you 25 discover if they have died or if they have perhaps left the Tennyson 6 Company Court Reporters London, England 01144-12424164 ucc 072968 24 1 country or what has happened to them. You may not, you are not 2 always concerned with whether they are alive or dead, you may 3 want to discover the diseases they have developed in the course 4 of the period. That is a more complicated study than one which S just requires you to find out the causes of their death. 6 Q Are there different types of epidemiologic studies 'that 7 are done? 8 A Oh yes, quite a number of different types. 9 Q Have you heard of proportionate mortality study? 10 A Yes. 11 Q What is that?. 12 A That is one in which you just record the causes of 13 death of a defined group of people, let us say, people working 14 in a particular industry and then you compare the proportions 15 of death from different causes in that group with the proportions 16 that you might expect from some other standard population, usually 17 the population of the whole country. It does not require you 18 to know precisely the number of people that you had originally j 19 in which these deaths occurred. You just require a list of all 20 the deaths you can get hold of. Let us say the deaths of all 21 the people actually working in a plant over a given number of 22 years in which you do not have to find out what has happened to 23 all the people who have left there, as in a cohort study, you 24 will find out what has happened to everybody. In a proportionate 25 mortality study you are merely concerned with the deaths that Tennyson & Company * Court Reporters London, England 01144-12424164 UCC 072969 25 1 you know about and you have not got any details of the whole 2 group in whom these deaths occurred. 3 Q What is it used for. Why Is it done? 4 A Well, it is commonly called a quick and dirty study. 5 You can get this information quite easily very often and can 6 get it quickly and by looking at the distribution of deaths,* the 7 different causes of deaths in this list of deaths that you have, 8 you can get an idea as to whether there is any excess or gross 9 excess of a particular disease and this will then provide you 10 with a hypothesis which you will then want to test by doing a 11 full scale cohort study or by doing another type of epidemiologic 12 study known as a case control study. 13 Q Are proportionate mortality studies used for cause and 14 effect of particular occupational disease? 15 A Not in general, no. In an extreme case you might say 16 the evidence obtained from a proportionate mortality study was I 17 l sufficient to give you pretty strong indications about a cause, 1 i 18 but normally speaking they are regarded as hypothesis-forming, 19 the basis for a full scale scientific study. 20 Q Are there weaknesses associated with the proportionate 21 mortality study? 22 A It is a question of the data. The data are fine, but 23 you may get an increased number of deaths from some causes, or 24 it appears to be an increased number of deaths because you have 25 a deficiency of deaths from other causes. You have a*group of Tennyson & Company - Court Reporters London, England 01144-12424164 UCC 072970 26 1 people who have very few accidents, let us say, or who have been 2 selected in such a way that they have very little chronic 3 respiratory disease. Automatically, the deaths that occur in 4 this group,will be disproportionately due to other causes, so 5 you cannot say there is an excess of one group of causes in 6 these workers because the alternative explanation may be there 7 is a deficiency of other causes. 8 Q I believe you have already described, but are there 9 other types of epidemiologic studies that are more accurate or 10 are more valuable to you? 11 A From the point of view of assessing cause and effect, 12 yes. there is another whole group of studies which we call case 13 control studies in which you start from the diagnosis of a 14 particular condition, let us say cancer of the lung. You get 15 a list, if you can, of all the patients admitted to a number of 16 hospitals with cancer of the lung and then you interview them 17 to find out what their past lives have been like, what chemicals! 18 they have been exposed to in the past, if that is what you are 19 interested in and then you take a group of people who have not 20 got cancer of the lung and find out what exposure they have in 21 their past lives, how they behave and compare the two and see 22 If there is any peculiar characteristic of the people who 23 develop the disease you are interested in. That can give very 24 important information about potential disease, but, of course, 25 to say that something is the cause of a disease, that*is only Tennyson & Company - Court Reporters London, England 01144-12424164 UCC 072971 27 1 done on the basis of the totality of the evidence of all sorts 2 and you have to take into account all the evidence that you can 3 obtain from many different sources* including* for example* the 4 extent to wtvich a new agent has been introduced into society* 5 the variation in the prevalence of it from one country to another 6 and how this correlates with the prevalence of the disease. .All 7 sorts of evidence like that has to be taken into account before 8 you can conclude that something is the cause of a particular 9 disease. t 10 Q Is epidemiology usually used to prescribe a particular n cause of a disease in a particular person? 12 A No* very seldom. It is used to discover the cause of 13 a risk to which a group of people - - of which a group of people 14 suffer. It can on occasions* epidemiological evidence will be 15 so strong that you can conclude that a particular individual has 16 developed a disease because of exposure to a particular cause* j 17 but that is unusual. 18 Q Sir Richard* I have heard of a term used called the 1 | 19 power of an epidemiologic study. What is that? 20 A Well* that is a complex concept. If you start from 21 the assumption that a particular mode of behaviour or exposure 22 to a particular chemical is going to cause a certain risk, let 23 us say a risk of someone developing a particular cancer* of 1 24 in 100 in the course of five years* then the power of the study, 25 what it means by the power of the study is the extent'to which Tennyson & Company - Court Reporters London, England 01144-12424164 UCC 072972 28 1 you will be able to be precise about the actual risk that people 2 in that group suffered. Your postulate was that 1 In 100 might 3 develop it in five years. You may say, well the power of this 4 study is only such that we will be able to exclude 5 per cent 5 of people developing it in five years because there are not - - 6 or the power of the study is such we will only be able to say 7 that not more than 5 per cent of the people will develop the 8 disease in five years. On the other hand, if you have a very 9 powerful study you might say, well we can boil down our con 10 clusions to a very fine limit. We can say that the risk in this 11 group must have been something between J per cent and 1J per 12 cent to developing the disease in five years. Then you would 13 say that is a pretty powerful study. 14 Q So it refers to the accuracy of the conclusions and 15 the ability to be accurate in those conclusions? 16 A It refers to the precision of the conclusion you can ! 17 draw, not to the qualitative conclusion, but to the quantitive j 18 conclusion. 19 Q What does the term standardized mortality ratio mean? 20 A This is a term we used to show we have taken account 21 of the peculiar age distribution of the population we are studying. 22 Many, many diseases vary in instance with age of the individual, 23 particularly diseases like coronary heart disease or cancer, they 24 tend to become much commoner as people get older. Therefore, 25 if you are comparing two population groups, you must compare Tonnyaon & Company - Court Reporter* London, England 01144-12424164 UCC 072973 29 1 people of the same ages. Obviously, also of the same sexes and 2 a standardized mortality ratio is a figure which you obtain from 3 your study, taking into account the peculiar age distribution 4 of the population you are studying. 5 Q When you are studying two populations and trying to 6 determine the causes of cancer, what is the difference between 7 those two populations? 8 A I am afraid I do not quite follow. 9 Q Say you are studying something like vinyl chloride and 10 you are trying to discover what effect it has and you have two 11 populations, one population would be exposed to vinyl chloride 12 and one would not? 13 A That is right. 14 Q Would you expect to see cancer in the group that was 15 not? 16 A It depends on the type of cancer. Most cancers occur ^ 17 for reasons which we do not know, throughout the whole world. 18 There is a background incidence of all types of cancer. Some 19 cancers are really quite common as a result of background factors 20 that are affecting the whole population. Others, on the other 21 hand, are extremely rare. So, when you are looking at your group 22 of workers, for example, exposed to vinyl chloride, the importance 23 of the background incidence will vary with the type of cancer 24 you are studying. If you are studying cancer of the lung which 25 is very common in the population for other reasons, then it will Ttnnyaon & Company * Court Reporters London. England 01144-12424164 UCC 072974 30 1 be quite difficult to tell whether vinyl chloride is causing 2 cancer of the lung in that population. On the other hand, if 3 you are looking at an extremely rare disease like angiosarcoma 4 of the liver*, a disease which only affects 1 in 10m people a 5 year, then if you find two or three cases in a group of 200 men, 6 you do not need any other evidence to indicate you have found 7 something pretty extraordinary. The conclusions you draw depends 8 very much on the type of disease you are studying and its 9 general incidence. 10 Q What does the term statistical significance mean? 11 A This is a term we use purely arbitrarily to indicate 12 the probability that your observation may have occurred by chance 13 and not be in any way due to the peculiarities of the group you 14 have been studying. Quite arbitrarily we take a probability of 15 1 in 20 as being something that we would not normally accept as 16 something that is likely to turn up, so if we find an excess of | 17 a particular disease which would only have occurred by chance \' i I 18 once in thirty times in that group, then you call that statisti- ! 19 cally significant and you think you have probably got some 20 peculiarity about the group, but it is only a guide. Statistical 21 significance does not tell you definitely whether a disease is 22 due to a particular environment or particular type of behaviour. 23 It just helps you draw a conclusion as to whether it is likely 24 to be due to the peculiarities of the group or whether it is 25 something that could be purely chance event because, after all. Tennyson & Company * Court Reporters London, England 01144-12424164 UCC 072975 31 1 not only 1 in 30, but 1 in 100 chances turn up every now and 2 again or otherwise no one would ever buy a lottery ticket! 3 Q Sir Richard, are you familiar with animal studies whicl 4 are used in cancer research? 5 A To some extent, yes. I am not a specialist in that 6 field but I have to take account of them in determining epidemio* 7 logical observations. 8 Q What are the advantages and disadvantages of an 9 epidemiologic study versus an animal study? 10 A Well, an epidemiological study, the great value of that 11 refers to the animal whose disease that you are trying to prevent 12 and you know that your findings are relevant to human beings. 13 The difficulty with it is that you usually cannot do an experiment. 14 You cannot do an experiment to produce disease in man so your 15 interpretation of epidemiological evidence is often open to 16 question. You can only take into account all the evidence and 17 eventaully you may be able to say it is sufficiently strong to 18 prove that a particular agent is a cause of a disease. With j 19 animals you can actually do an experiment. You can cause disease 20 in animals and so you can be confident about what the factor is 21 that has produced the increased incidence of disease in a par 22 ticular group of animals. What you do not know of course, is 23 whether humans will react in the same way as animals. You have 24 to extrapolate from one species to another and that is always 25 risky. By and large we can get good indications of what is Tnny*on & Company Court Reporters London, England 01144-12424164 UCC 072976 321 1 likely to happen to nan from studying different animal species, 2 but there is always the doubt in one's mind, perhaps a man may 3 not behave like a rat in this particular case. Perhaps he may 4 behave more like a guinea pig, in which case the reaction would 5 be quite different. 6 Q Do animals, different animals react differently from 7 time to time? 8 A Yes, they do. 9 Q I would like to change the subject. Are you familiar 10 with some of your colleagues in the field of cancer research and 11 epidemiology in the United States? 12 A Yes. 13 Q Have you heard of a gentleman called Richard Monson? 14 A Yes. 15 Q Have you heard of Leonard Chiazze? 16 A Yes. 17 Q Also have you heard of an Italian researcher by the 18 name of Dr Maltoni? 19 A Yes. 20 Q Have you heard of an occupational physician from 21 Cincinnati by the name of R. Michael Kelly? 22 A No. 23 Q Now 1 would like again to change gear. If we can go 24 and discuss a little bit the specific matter involved in this 25 case, vinyl chloride. Have you done any research involving i Tennyson & Company - Court Reporters London, Englsnd 01144*12424164 UCC 072977 33 1 vinyl chloride? 2 A Yes. 3 Q Would you describe that for me? 4 A Yes. It was not a very important piece of research, 5 we Just used the information that had been collected by the 6 chemical industries in this country on the number of cases of . 7 angiosarcoma of the liver, a particular cancer which is charac 8 teristically produced by vinyl chloride and we use the infor 9 mation collected from factories, industries throughout the world 10 where vinyl chloride had been used to try to get an estimate of 11 the amount of liver cancer because this disease, angiosarcoma 12 of the liver is commonly described as a liver cancer. We used 13 this information to try to predict how many more cases might be 14 expected to occur in industry. That was all this particular 15 piece of research was aimed at doing. 16 Q Since that time have you recently done a review of the I 17 literature or epidemiologic work of others on vinyl chloride? i 18 "v ! A Yes, I have done a review of the diseases produced by 19 vinyl chloride. 20 Q And that has resulted in the paper that has been 21 marked as Exhibit 2? 22 A This was published in the Scandinavian journal, "Work, 23 Environment and Health" in April this year. 24 Q Can you explain briefly what vinyl chloride is? 25 A Vinyl Chloride is a gas, a molecule, very important Tennyson ft Company - Court Reporters London, England 01144-12424164 UCC 072978 35 1 A 1 gathered a great deal of information about the health 2 of the workers exposed to large doses of vinyl chloride. 3 Q Old you do a comprehensive survey of the medical 4 literature? : 5 A Yes. 6 Q How did you go about doing that? 7 A 1 was provided with a list of publications by the 8 chemical industry, to which, of course, I then sought to add by 9 asking medical libraries to find out if there were any additional 10 articles that were relevant. 1 had to get some of the foreign 11 cnes translated and I read them all, decided which of them were 12 giving important information and then tried to summarise that 13 information and then when 1 had summarised all the information, 14 tried to make up my mind what it all meant. 15 Q Is this an area where the epidemiologic research has 16 been fairly extensive. Are there a lot of studies? 17 A There are quite a lot. There have been more studies v 18 on some other compounds but there have been quite a lot of i ii 19 studies on vinyl chloride. 20 Q Did you do this research before I ever contacted you 21 regarding working and testifying in this case? 22 A Oh yes, I was asked to do this, 1 cannot remember how 23 many years ago, about five years ago. I could not do it initiall), 24 I could not fit it into my timetable, but 1 effectively did it 25 in 1986 and finished the report in 1987. Tennyson & Company - Court Reporters London, England 01144-12424164 UCC 072979 36 1 Q And the results of that research have been recently 2 published? 3 A Yes, I made it a condition of doing the report that 4 I should befree to publish the results. 5 Q Was there any review of the results or change of the 6 results before they were published, not by editors but by the 7 CMA? 8 A Not of necessity. 1 did, in fact, send it to a 9 colleague of mine who worked in the industry to read through and 10 he suggested there were two points he thought I had not made 11 clear and I tried to improve in that respect and I then sent it 12 to the industry but there was no review from them after that. 13 Q In your opinion, was there any censorship or portions 14 of the article that they found unfavourable, that they asked you 15 not to publish? 16 A No, there was no such thing and indeed I made it a I 17 I condition of doing the review that I would publish exactly what ? 18 I thought. There was no possibility of any censorship. 19 Q Where was that published? 20 A In the Scandinavian journal "Work, Environment and 21 Health". 22 Q Is that a juried publication? 23 A Yes. 24 Q What does that mean? 25 A That is not a phrase we use in England. We say. Tennyson & Company - Court Reporters London, England 01144*12424164 UCC 072980 37 1 refereed. But yes certainly, that is a refereed journal. 2 Q What does that tern mean? 3 A That means the editor does not publish articles unless 4 he has sought opinions of other people in the field that it is 5 a reliable paper that deserves publication. 6 Q And this was done with your article? 7 A Yes. 8 Q What were the general conclusions you reached in this 9 study? 10 A I concluded that intense concentrations of vinyl 11 chloride such the people in the industry were exposed to before 12 the mid-60s in the United States and in England would produce 13 a normally very rare disease, angiosarcoma of the liver, a type 14 of cancer of the liver, that vinyl chloride might possibly 15 produce a small hazard of lung cancer. I could not be quite sure 16 about that, the evidence was not conclusive, but suggestive. 17 But, I thought that the evidence did not really suggest that V 18 vinyl chloride caused any other type of.cancer in humans. Two 19 or three other types of cancer had been suggested as being likely 20 to be caused by individual studies, but if you looked at the 21 totality of the evidence, you really did not find that there was 22 enough to bear this out. I would like to see some more work done 23 to check that there is not an excess of cancer of the brain and 24 cancers of the lymphatic system. On the whole I do not think 25 there is, but I think it would be important to confirA this Tenny*on & Company - Court Raportars London, England 01144-12424164 UCC 072981 38 1 negative conclusion by further observations. 2 Q Doctor, from the research that you have done, do you 3 have a general idea about the level of exposure to vinyl chloride 4 which existed and exists today in the vinyl chloride and poly 5 vinyl chloride manufacturing facilities? 6 A Yes. When vinyl chloride was first used in industry 7 it was not thought to be likely to be a hazardous agent and 8 people were exposed to very high concentrations of it of the 9 order of thousands of parts per million in the airt but it became 10 clear it did have a number of toxic effects, acute effects on 11 individuals. It was poisonous at that level and the levels were 12 reduced in the early 1960s, mid 1960s by ten-fold to something 13 of the order of several hundred parts per million, but it was 14 not until these cancers turned up that people realised that the 15 amounts that workers had been exposed to were still hazardous 16 and the levels were then quickly reduced to something of the 17 order of ten or five part?' per million and then Government i 18 agencies came in and said: "That is not low enough." 1 know 19 the industry really at first thought they could not get it much 20 lower but they have it down now so that no one is exposed to more 21 than one part per million. Very much lower than they used to 22 be exposed to when the risk of cancer was produced. 23 Q Do you have a general idea about the amount of vinyl 24 chloride exposure which existed in those factories where poly 25 vinyl chloride resin was used to make plastic products? Tennyson & Company - Court Reporters London, England 01144>1242416 UCC 072982 39*1 1 A I have not much knowledge of that. I decided in my 2 review not to study those plants, the workers In those plants, 3 because my understanding was that they really were not exposed 4 to levels of%more than ten or twenty parts per million or even 5 less and so it did not seem relevant. I Wanted to find out what 6 vinyl chloride could produce and* therefore, 1 wanted to look 7 at groups of people who had been exposed to hundreds of parts B per million and X did not cover the people that used polyvinyl 9 chloride and who might be exposed to small amounts of vinyl 10 chloride in my review. 11 MR DELLI BOVI: I am going to object to Dr Doll's last 12 answer dealing with levels of vinyl chloride monomer, for 13 lack of proper foundation. 14 BY MR BUNDA: 15 Q I provided you, Doctor, with documents relevant to the 16 levels of vinyl chloride exposures that existed in the Ohio plant 17 that Mr Dendinger and Mr Wallace worked in, have I not? 18 A Yes. i t | 19 Q What is your general understanding of what those levels 20 were as to what you have said before? 21 A My understanding is that those levels were low but not 22 as low as we like to see them now. 23 Q Sir Richard, have you come across any statistics which 24 are important to you with regard to the decrease and level of 25 exposure. 1 am speaking now of statistics involving those who Tennyson & Company - Court Reporters London. England 01144*12424164 UCC 072983 40 1 have incurred angiosarcoma of the liver? 2 A Yes. Well, the angiosarcoma of the liver we take as 3 the marker of exposure to substantial amounts of vinyl chloride. 4 My understanding from studying the register of angiosarcoma cases 5 which is maintained by Imperial Chemical Industries in England 6 and they send me copies of this up-dated register every year,' 7 my understanding is that there has not yet been a case of angio 8 sarcoma recorded in anybody who was first exposed after 1969. 9 That was someone, a case that developed in Germany. 1 think I 10 am right in saying that no cases have been recorded in American 11 workers who were first exposed after 1964. 12 Q What is the significance of that statistic to you? 13 A Well, it is suggestive, but it is not conclusive. It 14 is suggestive that the reductions in level in concentration that 15 took place in the mid 1960s had reduced the exposure of vinyl 16 chloride workers in the developed countries to levels at which 17 the risk of developing angiosarcoma of the liver is so low that i 18 you may not see any more cases. I cannot say you will not see i 19 any but you would only see one in a very large number of people. 20 1 have to qualify that though to some extent because cancers 21 take some time to be produced after individuals are first exposed 22 and this particular disease tends to occur only fifteen, twenty 23 years or more after first exposure. We had had one case occur, 24 I think nine years after, is the shortest, but we are just coming 25 up to a time now in which it is becoming really interesting that Tennyson & Company - Court Reporters London. England 01144*12424164 UCC 072984 41 1 no new cases are being recorded that have occurred as a result 2 of exposure limited to the period after the mid 1960s because 3 we are getting twenty, twenty-five years after first exposure, 4 but it will still take another five years, 1 would say, before 5 we can be confident that the reductions that took place in that 6 period were really adequate to eliminate or, if not eliminate., 7 nearly eliminate the risk of the disease. 8 Q Doctor, I would now like to address the specific 9 gentlemen involved in this case, Mr Dendinger and Mr Wallace and 10 the facts surrounding them. I provided you certain materials 11 regarding these two gentlemen? 12 A Yes. 13 Q You have seen certain medical records regarding their 14 cancers? 15 A Yes. 16 Q You understand that Mr Dendinger died of a colon cancer 17 and Mr Wallace died of a mucoepidermoid of the parotid gland? i 18 A Yes. 'v j 19 Q Do you have an opinion to a reasonable degree of 20 medical certainty about what is known by medical science about 21 these two types of cancers? 22 A I wish 1 could tell you what the causes of those two 23 types of cancers are. Cancer of the parotid gland is cancer of 24 the group of glands, the salivary glands and we really do not 25 know any causes of these particular types of tumours.' They are Tennyson & Company Court Reporters London, England 01144-12424164 UCC 072985 42 Ii 1 a little more common among Canadian Indians than any other 2 population. That may be a clue, but I do not know what Canadian 3 Indians do that would produce these diseases. They also occur 4 in families that have a high incidence of cancer of the breast. 5 These types of cancer sometimes occur in families with a genetic 6 susceptibility to cancer of the breast but I know of no cause 7 of cancer of the salivary glands and there is nothing to suggest 6 that vinyl chloride would cause that disease. Cancer of the 9 colon is a different matter. This is a common disease in 10 developed countries. There is quite a good deal of evidence to 11 suggest that most of the cases are determined by the diet of 12 developed countries, particularly the high content of fat and 13 the relative lack of fibre in the diet, but the evidence is not 14 conclusive. I think it is strongly suggestive that both these 15 two factors contribute to the development of the disease but 1 16 do not think any epidemiologist would wish to say he thought it 17 was proved that those factors were important. It is something 18 to do with conditions of life of the developed world throughout 19 Europe and North America and Australasia that leads to the pro 20 duction of these diseases but 1 cannot put my hand on my heart 21 and say what it is. I am confident that vinyl chloride does not 22 produce this disease. 23 Q Sir Richard, could you explain to the jury what is 24 known by medical science about the types of cancers which are 25 caused by vinyl chloride? Tennyson & Company Court Reporters London, England 0114412424164 UCC 072986 --- ---------------------------------------------- 431 1 A Yes. We must divide this into two categories of 2 animals and humans. In animals vinyl chloride produces the 3 angiosarcoma of the liver as it does in humans. It also produce! 4 squamous sarcoma of the zimbal gland in rats. It possibly 5 produces a few other cancers of the lungs. There was a belief 6 that It produced cancer of the haematopoeteic system and lymphati 7 system originally but this I think is differently interpreted. 8 Q Let us focus on humans. 9 A In humans it produces a particular type of cancer of 10 the liver and I frequently referred to angiosarcoma of the liver 11 intentionally. Cancer of the liver is rare in North America and 12 England but those cancers that do arise in the liver are usually 13 haepatomas, liver cancer cell tumours, but there is this very 14 rare type of cancer of the liver which arises from another type 15 of cell in the liver called an angiosarcoma and this is charac 16 teristically produced by vinyl chloride. I think there is 17 reason to suspect that it^may also cause cancer of the lung to 18 a small extent but that is not proven. I do not think it causes 19 any other cancer in humans. 20 Q Sir Richard, does the fact that as you have indicated, 21 there is research which indicates that vinyl chloride causes 22 cancer in one part of the body, the liver, mean that it can be 23 said that if there is cancer in another part of the body of some 24 one exposed to vinyl chloride, that vinyl chloride is the cause 25 of that cancer? Tennyson a Company - Court Reporters London, England 01144-12424164 UCC 072987 T 44 1 A No, It certainly does not mean that. From what we 2 know of the causes of cancer and we know now quite a lot, I 3 could give you a list of about fifty agents which cause cancer 4 in humans and with one exception of ionizing radiations which S will cause cancer in practically every tissue, these are all 6 site specific. They cause cancer in one or perhaps two or three 7 associated^organs but none in more. Tobacco smoke might be 8 regarded as an exception. That causes cancer in about seven or 9 eight organs. I am not sure of the recent count, but that is 10 hardly relevant to your question because tobacco smoke contains 11 3,000 chemicals and at least 25 different carcinogens. So, the 12 fact that produces cancer in so many organs is irrelevant to 13 your question. A specific chemical so far as human experience 14 goes, produces cancer usually or pretty well always in a very 15 limited number of organs. The only exception I can think of is 16 ionizing radiation which will produce cancer in practically 17 every organ. .v f i 18 Q Doctor Doll, I would ask that you base your answer now = 19 and give us an answer to this to a reasonable degree of medical 20 certainty because that is what the American Courts require. My 21 question to you is this; Based upon your training, experience 22 and knowledge in the field of medicine and epidemiology and 23 based on your research into the area of cancer, specifically as 24 it relates to vinyl chloride, do you have an opinion to a 25 reasonable degree of medical certainty as to whether vinyl Tennyson & Company Court Reporters London, England 01144-12424164 UCC 072988 45 1 chloride was a contributing cause of the parotid gland cancer 2 of Mr Wallace? 3 A Yes I do have. 4 Q What is your opinion? 5 A That it did not cause that cancer. 6 Q What is the basis of that opinion? 7 A The basis of that opinion is that of the workers who 8 have been studied, that had been exposed, to very large amounts 9 of vinyl chloride, there has been no excess of tumours of that 10 sort and it is not produced in animal experiments either. 11 Q Mr Wallace vas exposed, you indicated, to a lower dosel 12 A I have only the data that you presented me with of the 13 report of the industrial hygienist and that certainly implied 14 it was a much lower dose. 15 Q Does that have any relevance to your conclusion? 16 A Well, it just strengthens the conclusion because one 17 would not expect doses of J.,000 parts per million to produce that i 18 type of cancer. 19 Q What did your review of the literature indicate? Are 20 there any indications that that type of cancer was caused by 21 higher levels? 22 A No, no indications at all. 23 Q Based on your training, experience and knowledge in 24 the fields of medicine and epidemiology and your research and 25 review of the medical literature in the area of cancer. Tennyson & Company * Court Reporters London. England 01144-12424164 UCC 072989 i 46 1 specifically as it relates to vinyl chloride, do you have an 2 opinion to a reasonable degree of medical certainty as to whethei 3 vinyl chloride was a contributing cause to the colon cancer in 4 Hr Dendinger1? 5 A Yes, 1 do have. 6 Q What is your opinion? 7 A That it was not such acontributory cause. 8 Q What is the basis of your opinion? ~ 9 A Studying these statistics of men exposed t;o very high 10 doses of vinyl chloride and comparing the risk of colon cancer 11 in those men compared with the risk of developing colon cancer 12 of people in the country at large who were not exposed to vinyl 13 chloride. 14 Q Are these conclusions of yous borne out or indicated 15 in the article you recently published? 16 A Yes. 17 Q Sir Richard, are you familiar with the 1981 study done I 18 by an epidemiologist by the name of Leonard Chiazze? j 19 A Yes. 20 Q This was done of workers developing cancer using poly 21 vinyl chloride resins? 22 A Yes. 23 Q These were in areas like Mr Dendinger and Mr Wallace? 24 A My understanding is that that is correct. 25 Q What type of study was that? Tennyson & Company Court Reporter* London, England 01144-12424164 UCC 072990 47 1 A That was a proportionate mortality ratio study. 2 Q And we have already discussed the purpose of that? 3 A Yes. 4 Q Can you remind the jury what that study is used for? 5 A It is used as hypothesis-forming to see if there is 6 any suggestion there might be a specific hazard among a particu 7 lar group of people Investigated. 8 Q Do you recall in that particular study there was a 9 suggestion or a hypothesis that perhaps digestive cancer shoved 10 some increase in this group? 11 A Yes, there was indeed. 12 Q How do you resolve that study with the results of your 13 study? 14 A This, as we have said, was a proportionate mortality 15 ratio study and the relatively high proportion of deaths due to 16 cancer of the colon on that study in comparison with deaths of 17 i people of the same sex andage in the United States as a whole, j 18 was influenced by the fact that the people investigated had a 19 very low proportion of deaths from other diseases, some other 20 diseases, particularly accidents and respiratory disease and this 21 low proportion automatically results in there being a high 22 proportion of some other cause of death, particularly cancers 23 and the proportion of deaths due to cancer as a whole was in 24 creased in that study. Now, many people - I am surprised 25 Dr Chiazze did not do this - prefer to use what we call a cancer Ttnnyaon & Company- Court Raponer* London, England 01144-12424164 UCC 072991 48 1 proportional mortality ratio study in which you just look at the 2 proportion of different cancers attributable to cancers in 3 different sites. This is a better indication of a possible risk 4 because caAcer as a whole is not really influenced by the 5 selection of workers into a particular Industry as the risk of 6 developing cancer as a whole has been shown in many studies 7 where there is no special hazard, to be much the same as in the 8 general population. So, if you look at the distribution of 9 different types of cancer within all the cancers you are much 10 more confident you have something odd if you find that one of 11 those cancers, one type of cancer, shows a higher ratio. 1 12 cannot do precisely a proper cancer proportional mortality study 13 on the basis of the published data, but I can make an approximate 14 estimate. If you do that* if you examine the different types 15 of cancer that have caused death, then the excess - and there 16 is some excess from colon cancer - ceases to be what we call I 17 technically significant. vIt is not quite significant. Mind you*j 18 if it was significant it would not lead to the conclusion that 19 the work had caused cancer of the colon because if you look at 20 some twelve or fifteen types of cancer* the chances are that you 21 will find that one is unexpectedly common. After all* a 1 in 22 20 chance turns up 1 in 20 times. The statistical test is only 23 a guide to one's thought* that my assessment of the data is that 24 if you look within the different types of cancer there is not 25 really any surprising excess numbers of deaths from cancer of Tennyson & Company - Court Reporter* London, England 01144-12424164 ucco9W UCC 072993 49 1 the colon. 2 Q Of the other studies that you have reviewed, have you 3 found any that have concluded that there is an increased risk 4 of Incurring cancer of the colon from vinyl chloride? 5 A 1 have to qualify my answer to that. My principal 6 studies that I thought gave the best indications of hazards 7 irrelated to vinyl chloride which was 49 plants in the United 8 States, England, Canada and Italy, they actually gave rise to 9 a smaller number of deaths from cancer of the colon than would 10 be expected from the general population. I think it was 30 11 deaths whereas you might have expected 43. This is not a sur 12 prising deficiency, it is quite within reasonable chance variation 13 Then 1 looked at another 7 studies that I called subsidiary 14 studies which, for a variety of reasons did not give such good 15 evidence. The latent periods were not long enough. Various 16 other reasons. There was a small excess, 1 think 39 against 35 17 expected, but even if you ^added those into what I call the 18 principal studies, you still find a deficiency of deaths from 19 cancer of the colon. I am not suggesting vinyl chloride protects 20 against developing cancer of the colon, this deficiency is just 21 the sort you would expect quite easily by chance in a study of 22 this size, but looking at the evidence as a whole 1 am quite 23 confident that there is no suggestion at all of any excess of 24 cancer of the colon on people exposed to high doses *of vinyl 25 chloride. f Tennyson & Company - Court Reporters London, England 01144*12424164 UCC 072994 50 1 Q We talked about the power of studies before. The stud) 2 which you recently published based upon a review of ,the other 3 studies that you looked at, the subsidiary studies and the four 4 main studies, how does the power of your study compare to that 5 of Dr Chiazze? 6 A Well, it is qualitatively entirely different. The 7 studies 1 reviewed give firm evidence. Dr Chiazze's study does 8 nothing more than throw up a hypothesis for testing. Nobody with 9 any experience of epidemiology could draw a conclusion about the 10 cause of disease from the results of Dr Chiazze1 s study. 11 Q Dr Chiazze's study calls for further investigation? 12 A Yes. 13 Q Was your study the type of further investigation that 14 was called for? 15 A My review was of vinyl chloride workers specifically 16 exposed to the gas itself or the manufacture of polyvinyl chloride. 17 I think Dr Chiazze would say that he was calling for a study of j 18 people working with polyvinyl chloride because after all, there are 19 other chemicals to which those people are exposed and the fact 20 that we do not see anything in these diseases that he hypothesized 21 might be produced by vinyl chloride, the fact that we do not see 22 them appear in people that were intensively exposed to it, does 23 not mean to say there was not something in that industry that 24 caused a risk of colon cancer. That, I think, needs.investigation, 25 but that is a working hypothesis, nothing more. T Tennyson A Company - Court Reporters London, England 01144-12424164 UCC 072995 51 1 Q In your opinion, again to a reasonable degree of medical 2 and scientific certainty, is there any scientific basis for 3 claiming either of these two cancers were due to the. exposure 4 to vinyl chloride? 5 A There is no reason for concluding that at all. 6 MR BUHDA: Thank you very much, that is all the 7 questions I have. 8 (Whereupon there followed a discussion off the record) 9 (Whereupon there followed the luncheon adlournfaent) 10 CROSS EXAMINATION 11 BY MR DELLI BOV1s 12 Q My name is Kirk Delli Bovi, we have been introduced 13 before. I represent the Plaintiffs in this case and I have a 14 few quesitons 1 would like to ask you this afternoon. Is it 15 your understanding that Mr Dendinger and Mr Wallace were employee 16 not in the vinyl chloride industry or in the polyvinyl chloride 17 producing industry, but in the PVC fabrication industry? i ! 18 A Yes. 19 Q Can you tell me what epidemiological or other studies 20 you are aware of that pertain to workers in the industry in which 21 Mr Dendinger and Mr Wallace worked, that is the PVC fabrication 22 industry? 23 A There is one by Dr Chiazze and a colleague. There is 24 a Swedish study, I am afraid I forget the names of t.he authors 25 and there has been a recent study, 1 think unpublished, by a Tennyson & Company - Court Reporters Condon, England 01144*12424164 UCC 072996 52 1 doctor of the particular industry in which Mr Wallace and 2 Mr Dendinger worked. Those are the only three thatI can recall 3 at the moment. 4 Q in terms of your opinions in this case, have you reliec 5 upon any of the three studies that you have just cited, per 6 taining to workers in the PVC fabrication industry? 7 A I-have not specifically studied the PVC fabrication 8 industry. I have studied the effects of exposure to vinyl 9 chloride and the evidence 1 have given has been in relation to 10 exposure to vinyl chloride. 11 Q In the paper that you wrote for the Scandinavian 12 journal "Work, Environment and Health", you indicated, did you 13 not, that in formulating opinions concerning the aetiology of 14 cancer, it is important to look at all of the evidence? 15 A Yes, whether I said it in the paper I do not know, but 16 I certainly believe it. 17 Q Now, when you prepared your paper for that Scandinavian! 18 journal, did you include/&i?e end of it a list of the references 19 that you consulted in preparation of that work? 20 A Yes. 21 Q And there are a list of some fifty references that you 22 consulted that you relied on in whole or in part or to a limited 23 extent in preparing that work? 24 A Yes. 1 did not read one of them actually,* it was a 25 Russian one. 1 only quoted it on the basis of somebody else's Tennyson & Compsny Court Reporters London. England 01144-12424164 UCC 072997 53 1 analysis of it* 2 Q Did you rely to any extent on Dr Chiazze's study in 3 authoring your paper entitled "Effects of exposure to vinyl 4 chloride --an assessment of the evidence"? 5 A No, 1 did not. I read the paper but I specifically 6 excluded it. As you will see, I stated in that paper that I did 7 not Include in my review, reports of polyvinyl chloride fabri 8 cators as it was my understanding that the amount of vinyl 9 chloride which people in that industry would have been exposed 10 to was substantially less than people were exposed to in the 11 PVC manufacturing industry and my specific concern was with 12 vinyl chloride, not with the effects of any other chemicals that 13 might be found in the fabricating industry. 14 Q What was the source of your assumption or your under 15 standing that the levels of worker exposure in the PVC fabri 16 cating industry were lower than those in the PVC resin producing I 17 industry? i 18 A Two items of information. One, the information that j 19 I was given by medical officers in Imperial Chemical Industries 20 with whom 1 am on professional terms and the other was the 21 absence at that time of reports of angiosarcoma of the liver 22 which I regard as an indicator of vinyl chloride exposure in 23 people in industries other than the vinyl chloride monomer of 24 polyvinyl chloride manufacturing industries. 25 Q Have you ever seen any data from any plants in the Tennyson & Company * Court Reporters London, England 01144-12424164 UCC 072998 54 1 United States comparing levels of vinyl chloride in the work 2 place atmospheres in fabrication plants as opposed to resin 3 manufacturing plants? r 4 A I have no direct knowledge of levels in American 5 fabrication plants other than the information provided to me by 6 the investigators at the particular plant in which Messrs Wallact 7 and Dendinger were employed, but as to the rest of the industry 6 I have no personal knowledge of it. 9 Q When you were presented with the data from theCbrysler 10 facility where Mr Dendinger and Mr Wallace were employed, were 11 you given any understanding as to the time frame encompassed by 12 that data? 13 A Yes. I am speaking from memory now. I would like to 14 check it, but I think the observations were made around the 15 middle 1970s but if 1 am wrong, please tell me. 16 Q Are you aware that the observations all the data that j 17 was furnished to you regarding vinyl chloride levels in the work-j 18 place atmospheres in that plant were all subsequent to the public 19 announcement of the Goodrich nagiosarcoma deaths? 20 A I think they must have been, yes. I am assuming they 21 were. 22 Q Is it your understanding, based upon your knowledge 23 of the industry, that the workplace levels of vinyl chloride 24 would have been higher prior to the public announcement of the 25 Goodrich angiosarcoma deaths? * Tennyson & Company Court Reporters London, England 01144-12424164 UCC 072999 55 1 A The levels in the manufacturing industry were certainly 2 higher before that but whether they could have been/higher in 3 the PVC fabrication industry 1 do not know because I do not know * 4 how much vinyl chloride could have been released from manufac 5 tured PVC. I would be guessing. It does not necessarily follow 6 that they were higher, but they could have been higher. 7 Q Do you have any knowledge as to the mechanism by 8 which workers in a PVC fabrication plant would become exposed 9 to vinyl chloride? 10 A No intimate knowledge, no. 11 Q Have you been provided with any information by the 12 PVC manufacturers as to the method by which PVC fabrication 13 workers can be exposed to vinyl chloride? 14 A Not that I would call any serious account, no. 15 Q I am going to hand you what I have marked as Plaintiffs 16 Exhibit Doll 2. Could you identify that, sir, as the work of 17 Dr Chiazze that appeared in the scientific journal in the United j 18 States in 1981. (Document handed to the witness) 19 A Yes. 20 Q In terms of the size of that study, looking at the 21 number of deaths Dr Chiazze analysed, how does the size of 22 Dr Chiazze*s study compare to the size of all the studies that 23 you considered in preparing your Scandinavian journal? 24 A Insofar as it relates to exposure to vinyl: chloride, 25 I cannot say, because Dr Chiazze*s study does not say what Tennyson & Company - Court Reporters London. England 01144-12424164 UCC 073000 56i 1 proportion of the 17,000 odd workers that were probably involved 2 were exposed to vinyl chloride, though he does say somewhere that 3 the proportion - at least if my memory is correct - rthat it was 4 only a relatively small proportion so Z cannot answer that 5 question except to say to the best of my belief it is a very mud 6 smaller total number of people exposed to vinyl chloride than 7 in the studies which 1 reviewed. 8 Q My question. Dr Doll, dealt with the number of worker 9 deaths that Dr Chiazze analysed compared to the total number of 10 deaths analysed in the review that you did. 11 A The total number is slightly less than the total numbei 12 in the review that 1 did. 13 Q Dr Chiazze's study involved the deaths of 3,847 worker^? 14 A So 1 believe, yes. X think my studies covered some 15 5,000 workers, if I remember correctly, but I would need to 16 check. Some 5,000 deaths, I mean. 17 Q Why don't we take a look at that if we could. Do you 18 have a copy of your report handy? Could you indicate to me. 19 Dr Doll, the total number of deaths that were analysed by you 20 in your review? 21 A Yes, I am just trying to check. It must have been less 22 (Pause) No, I am sorry, my memory was at fault. I was thinking 23 of another review I have just done on formaldehyde. The total 24 number is nearer 2,000, not 5,000. 25 Q Could we break that down please for the individual Tennyson & Company - Court Reporters London, England 01144-12424164 ucc 073001 ---------------------------------------------- 57 1 studies you analysed. How many deaths were involved in the 2 United States? * 3 A 1.136. 4 Q And in the United Kingdom study? 5 A 760. 6 Q Canadian? 7 A 59. 8 Q And the Italian study? 9 A 66. 10 Q So in terms of the total number of deaths encompassed 11 by the studies, the Chiazze study looked at substantially more 12 deaths than all of the studies covered by your review? 13 A Yes, that is true. 14 Q As a result----15 A Just a minute, let me see what the subsidiary studies 16 were. Where are we now? We will have to add these up. (Pause) j 17 Yes, I think the total of the subsidiary studies still probably 18 come to somewhat less than the total reported by Dr Chiazze. 19 Q Now in terms of the conclusions that Dr Chiazze drew 20 from his proportional mortality ratio study, he determined that 21 there were statistically significant increases in cancers of the 22 large intestine in both the male and female deaths, did he not? 23 A No, he did not. His sort of study can tell you nothing 24 aboutthe incidence and consequently the increase in the amount 25 of cancer. What he showed was that if the distribution of deaths Tannyaon & Company - Court Raportars London, England 01144-12424164 UCC 073002 58 1 were to be expected to be the same as the distribution of deaths 2 in the American population of people of the same sex and the same 3 age, then the.sort of distribution that he observed vas unlikely 4 to have been obtained by chance, but that says nothing about an 5 increase or decrease in them because that is a purely proportion 1 6 distribution and a high proportion of one cause of death may be 7 due to a low proportion of another type of death, so you can 8 draw no conclusions about the actual incidence of the disease, 9 of mortality from the disease as Dr Chiazze is careful to point 10 out in his study. 11 Q Let me read to you, doctor, one of the sentences from 12 Dr Chiazze's conclusion and ask you whether you agree or disagree 13 with his statement: "PMRs are significantly different from unit) 14 for all cancers and for cancers of the digestive system among 15 both white males and white females". 16 A Yes, that is what I have just been saying. It is in ( 17 a different form, but essentially what 1 say. 18 Q So, in terms of comparing PVC fabrication employees i 19 to the general population. Dr Chiazze found statistically signifi 20 cant increases in the proportion of large intestine cancers in 21 both the male and female PVC fabrication workers? 22 A No, 1 do not think you could say significant increases. 23 He would say significant differences in the distribution and 24 this may have been due to significant decreases in the other 25 causes. So, a proportional mortality study of the sort he did Tannyson & Company - Court Reporters London, England 01144-12424164 UCC 073003 59 1 is not capable, as Dr Chia2ze points out in his article, of 2 telling you whether there is an increase or not. He is showing 3 that the distribution is different and now we have to assess and 4 try to determine why the proportion is different. 5 Q One of the limitations you indicated in your direct 6 examination on Dr Chiazze's study, was that the increases in the 7 large intestine cancers may have been attributable to correspond 8 ing decreases in other causes of death, for example, accidental 9 death, suicides, heart disease, things of that nature? 10 A Yes. 11 Q And you indicated in your direct examination that a 12 cancer proportionate mortality ratio study would have been a 13 better indication of the possible risk and that if that calcu 14 lation had been done, you would have been much more confident 15 that something odd had occurred? 16 A Yes, it would have been a better basis for producing 17 a hypothesis. ,v 18 Q Dr Doll, since reviewing Dr Chiazze's work, have you 19 made any effort to take Dr Chiazze's data and determine the 20 cancer proportionate mortality ratios for the total number of 21 cancers and for the large intestine cancers? 22 A Yes. 23 Q Have you brought any of those calculations with you? 24 A No, I have not brought them with me on paper, I have 25 brought them in my head. ? I i i Tennyson & Company Court Reporters London, Englend 0114402424164 UCC 073004 60 1 Q Your opinion was that if Dr Chiazze's PMR calculations 2 for total cancers and large intestine cancers were converted to 3 CPMRs, that the increased proportions of total cancer deaths and 4 large intestine cancer deaths would not be statistically signifi 5 cant? 6 A 1 must qualify that statement as 1 did earlier by 7 saying I could only make an approximate calculation on the basis 8 of the data available to me and the approximate calculation I 9 made suggested they were not statistically significant but I 10 would not exclude the possibility that if a proper cancer 11 proportionate mortality ratio was done, they would just be on 12 the other side of the 1 in 20 significance level which we usually 13 use, purely arbitrarily, to decide what is significant or not. 14 I think only Dr Chiazze could make such calculations, as you need 15 to have the basic data by broken down small age groups and 16 different calendar years. 17 Q So, it is your belief then that if Dr Chiazze*s PMR 18 figures were converted to CPMR figures, that they would still i i 19 show an elevation in the incidence of large intestine cancers? 20 A 1 am sure they would show an elevation in comparison 21 with the proportion of deaths normally attributed to cancer of 22 the large bowel In the American population, but 1 am not at all 23 sure that that elevation would be such that one would regard it 24 as being a particularly unusual event. 25 Q Do you attach any significance to the fact* that in his Tennyson & Company - Court Reporters London. England 01144-12424164 UCC 073005 61 1 PMR study. Dr Chiazze found increases in the proportion of large 2 intestine cancers of statistical significance for both males and 3 females? 4 A Not particularly, no. I suppose insofar as it implies 5 anything, if it were to be regarded as implying an occupational 6 hazard, it would weigh against it as women would be unlikely to 7 be employed on the same type of occupation as men. 8 Q Was there any indication in Dr Chiazze's study that 9 the women employees that he surveyed were performing different 10 jobs than the male employees? 11 A I cannot remember. 12 Q Would you like to take a look at his study and see if 13 it draws any such distinction? 14 A I am afraid it might take me five minutes to read it. 15 Q Certainly. Would you like to go off the record? 16 A Yes please. 17 (Off the record! i 18 BY THE WITNESS: 19 A Yes, I have read the paper and there is a strong 20 implication that there is different exposures for men and women 21 but no specific statement to that effect. I have drawn that 22 conclusion from ordinary experience of factories and the fact 23 that 72% of the women had no exposure to vinyl chloride and 12.6% 24 had improbable exposure and that a proportion of the- workers were 25 office and clerical workers. So, it seems to me the'ordinary Tannyaon & Company Court Reporter* London, England 01144-12424164 UCC 073006 62 1 conclusion to be drawn from that was that the women did different 2 Jobs from the men but Or Chiazze does not state that in his paper. 3 BY MR DELLI BOVIs 4 Q That is am implication you have drawn from his work? 5 A Yes an implication 1 have drawn from his paper. 6 Q In his study. Dr Chiazze found statistically different 7 increases in the proportion of total cancers, large intestine 8 cancers and others and unspecified cancers in both males and 9 females, did he not? 10 A Would you mind repeating that, I missed the first part 11 of the question? 12 Q In his study. Dr Chiazze reported statistically signifi 13 cant increases in the proportion of all cancers, large intestine 14 cancers and other and unspecified cancers in both males and 15 females? 16 A No, I do not think he reported significant increases 17 in the proportion of cancels due to large intestines. He reported j 18 significant differences in the proportion of total deaths due 19 to large bowel cancers. We pointed out earlier that a cancer 20 proportionate mortality study probably did not show a significant 21 increase in the proportion of cancer deaths due to large bowel 22 cancer. 23 Q I would like you to take a look, if you would, at eithe r 24 Table 3 of Table 4 from Dr Chiazze1 s study, which ever one you 25 prefer to work with. > Tennyson A Company Court Reporters London. England 01144-12424164 ucc 073007 -- "eT 1 A This is the second publication, is it not? 2 Q Yes, it is. The first one reports it in terms of 3 United States mortality. % You do not mind if I look rover your 4 shoulder, 1 did not bring another copy. Table 3 reports using 5 U.S. mortality up to 1968. Table 4 shows U.S. mortality figures 6 for individual years between 1964 and 1973. Would you feel more 7 comfortable using the individual years? 8 A It is not that I would feel more comfortable, the data 9 for the individual years are the data that are remotely relevant. 10 The data for using the single year for comparison was something 11 to provide a further indication of what the results might be but 12 neither Dr Chiazze nor myself would attach any significance to 13 the data in Table 3 when we have the data in Table 4 available. 14 Q Let us use Table 4 then. In terms of all cancer among 15 male PVC fabrication employees, what was the PMR that Dr Chiazze 16 calculated? 17 A For what? A i i 18 Q All cancers among male PVC fabrication employees. 19 A 1.1567. 20 Q Did Dr Chiazze determine that that figure was statisti 21 cally significant? 22 A Yes, he showed it was significantly different from the 23 proportion to be expected from the distribution of the deaths 24 in the U.S. population at the same period. 25 Q Can you determine by what percentage the figure' Tennyson A Company - Court Reporters London, England 01144-12424164 UCC 073008 to 1 represented an increase over that expected in the general 2 population? 3 A I do not think that necessarily indicated -any increase 4 in cancer mortality in the general population at all. It is 5 reflecting the fact that there were relatively few deaths from 6 accidents in this population and very few from diseases of the 7 respiratory system and cirrhosis of the liver. 8 Q And the decrease in those deaths is largely attribu 9 table to what has been called a healthy worker effect? 10 A Healthy worker effect is a very complex phenomenon 11 which has two or three components in it. In this case it reflects 12 what is a common - - it partly reflects what is a common 13 experience of any employed workers compared with the national 14 expectation, that is a reduction in the mortality of a number 15 of important diseases but, of course, in some industries the 16 accident rate may be a good deal higher than in the population 17 at large. Here we have an industry with a relatively low accident t 18 rate. I would not call that a healthy worker effect. That is 19 an effect of a well run industry or an industry with very little 20 hazards. The healthy worker effect is composed of several 21 components, one of which is the effect of observing a mortality 22 in a group of people who are healthy enough to start employment 23 when you begin and the first few years of any follow up study 24 invariably shows a low mortality for the first few years because 25 you have, by definition, included only people who were healthy Tennyson & Company - Court Reporters London, England 01144-12424154 UCC 073009 65 1 to be In employment at the beginning, but then this wears off 2 with the passage of time. Then there is a second aspect of the 3 healthy worker effect which is that people with certain chronic 4 diseases that are liable to give rise to high death rate, do not 5 get employed in industry, so that they are a selected population 6 and this often gives rise to low mortality, for example, from 7 chronic respiratory disease or from cirrhosis of the liver. 8 Q Before you finish your answer, the Court Reporter has 9 indicated we are about to run out of video tape so why don't we 10 change the tape. 11 (Whereupon there followed a discussion off the record) 12 (Whereupon there followed a short adjournment) 13 BY MR DELLI BOVI: 14 Q Dr Doll, have you concluded your answer? 15 A Yes. 16 Q With that answer in mind, can you tell me whether or 17 not the lower reported death rates/5&?l proportionately lower j 18 death rates in Dr Chiazze's studies for causes other than cancer.j 19 are attributable to a significant extent to the healthy worker 20 effect? 21 A I cannot say for certain, I would expect they were. 22 Q Going back to the male fabrication employees and all 23 cancers and the PMR of 1.1567 that Dr Chiazze reported, what does 24 that Indicate in terms of the proportion of male employees who 25 died of cancer versus the proportion of people in the general Tennyson & Company Court Reporters London. England 01144-12424164 UCC 073010 66 1 population that died of cancer as opposed to some other cause 2 of death? 3 A I am not sure. I should have to do a calculation. 4 Of course* 'another factor which has to he taken into account is 5 this comparison is a comparison with the whole of the United 6 States and not with a comparison with the people of Ohio which 7 would, of course, again alter the proportions, but 1 am afraid 8 I cannot answer your question without some calculations. 9 Q Let me ask it another way. If male PVC fabrication 10 workers were dying of cancer as a proportion of the total deaths, 11 at the same rate as the general population was, would the PMR 12 be 1.00? 13 A I think I will have to ask you to repeat that question. 14 Q Sure. 15 A Would you take it at dictation speed so I can get it 16 down? 17 Q Certainly. .v i i 18 A Or perhaps the simplest thing would be to ask the 19 Court Reporter to read it to me. 20 Q Whatever your preference is. (To the Reporter) Would 21 you read the question back, please? 22 (The Reporter read back the relevant passage) 23 BY THE WITNESS: 24 A Yes, well I have got that question now and I am afraid 25 it is a nonsense question because it is confusing proportions Tennyson & Comptny Court Reporters London, England 01144*12424164 UCC 073011 67 1 and rates so there is no possible way in which I can answer it. 2 BY MR DELLI BOVIs 3 Q How would you like the question phrased so" you can m 4 answer it in order to tell me why Dr Chiazze concluded that his 5 figure of 1.1567 for the male PVC fabrication cancer employee 6 deaths was statistically significant? 7 A That is quite simple. That is a different question 8 altogether. What he wss testing was the comparison of the dis 9 tribution of the causes of death as recorded in the deaths that 10 he knew about with the distribution of the causes of death as 11 recorded nationally at the same time and what he was able to 12 conclude was - and I would agree with him in this - that the 13 proportion of deaths in this group was a different proportion 14 from that recorded in the general population and that the fact 15 that it was different was unlikely, though not impossible, 16 unlikely to be due to chance, though it might be, but I would 17 agree with him that it probably was not. 18 Q That it was not due to chance? 19 A I would agree with him that it was probably not due 20 to chance because I can think of a lot of better reasons, but, 21 of course, it could be. 22 Q The probability that it was due to chance as opposed 23 to some other factor was less than 2QZ? 24 A 1 think you mean less than 5Z. 25 Q Less than ----- Tennyson A Company Court Reporters London, England 01144-12424164 ucc 073012 68 1 A Well again, you cannot answer that question. That is 2 not what the statistic says. That statistic does not tell you 3 what the probability is that it was a particular figure. What 4 it tells you is that if the distribution had been the same as 5 that of the national population over the sane period, in only 6 1 in 20 comparable studies would the PMR have been as great as 7 that found, or greater. 8 Q So, the odds are 1 in 20 that that particular finding 9 was a chance finding? 10 A This could have occurred by chance once in twenty times 11 or actually he says the probability is less than 1 in 20. I do 12 not know how much. Something between 1 in 20 and 1 in a hundred. 13 Q Can we fairly say then that he was confident to the 14 95% level that his finding was due to something other than chance 15 A No, that is deduction which no statistician would make. 16 You cannot have levels of confidence. You might be 100% con- j 17 fident it was due to chance even though it was, it appeared on 18 paper to be a very improbable thing. For example, if I took a ! i < 19 dice out of my pocket and threw it six times and it came up six 20 every time, I would not be 95% confident that was not due to 21 chance. I would be 100% confident it was due to chance although 22 it was a very improbable event, so you cannot draw any conclusion s 23 about the confidence with which you draw a conclusion about the 24 meaning of the findings. That is based on a whole lot of other 25 evidence. > Tennyson & Company Court Reporter* London, England 01144-12424164 UCC 073013 69 1 Q In terms of the male PVC fabrication employees cancer 2 deaths, the proportion of deaths among those workers was different 3 to a statistically significant level from the proportion of 4 deaths in the general population? 5 A In the United States over the same period, yes, 6 Q And Dr Chiazze came to an identical result and identi 7 cal finding with respect to the female PVC workers? 8 A Yes. 9 Q Again, as with the male, the odds of that finding in 10 the female PVC fabrication workers was 1 in 20? 11 A Less than. 12 Q Less than 1 in 20? 13 A Yes. 14 Q And Dr Chiazze came to a similar conclusion with 15 respect to the proportion of large intestine cancer deaths among 16 male PVC fabrication employees? 17 A Yes. I ' 18 Q And also with respect to the female employees in that 19 category? 20 A Yes. 21 Q Then with resepct to the other and unspecified cancers. 22 Dr Chiazze again came to a statistically significant finding, 23 did he not? 24 A Yes. 25 Q Both with regard to the male employees and with'regard Tannyaon A Company-Court Reporter* London. England 01144-12424164 IJCC 073014 7tr 1 to the female employees? 2 A Yes. 3 Q Have you reviewed at all. Dr Doll, in preparation for * 4 your testimony today, the 1976 study of Baxter and Fox? 5 A No. 6 Q Do you know whether or not in their study they reportec 7 an increase' in mortality due to stomach cancers? 8 A 1 am afraid you will have to remind me of this study, 9 I forget it. 10 Q Baxter and Fox Angiosarcoma of the Liver in PVC 11 Fabricators, an article that appeared in the Lancet at page 245 12 in 1976. Have you reviewed that study of PVC fabricator employees 13 prior to testifying here today? 14 A No. I am sorry, I will have to look at the paper. 15 1 do not think 1 have. 16 Q 1 did not bring the paper with me. All 1 have is the 17 reference to the paper. ^ 18 A Can you remind me of the reference again? 19 Q Baxter and Fox* Angiosarcoma of the Liver in PVC 20 Fabricators, an article that appeared in the Lancet on page 245 21 in 1976. 22 A I cannot recall having reviewed that. Why I am hesi 23 tating is because I am not sure whether those workers were sub 24 sumed subsequently into the study done by Jones of all vinyl 25 chloride workers in this country. I am not sure if ihey were Tennyson & Company - Court Reporters London, England 01144*12424164 UCC 073015 fn 1 subsumed into this. 2 Q Wells the Baxter and Pox could not be subsumed in Jones' 3 work because Baxter and Fox dealt with PVC fabrications while 4 Jones dealt with FVC manufacturing employees and vinyl chloride 5 manufacturing employees. 6 A If it was purely PVC fabrication and did not involve 7 the manufacture of vinyl chloride or polyvinyl chloride in the 8 same plant* then I have not reviewed It and I have specifically 9 stated that 1 excluded such data from my review. 10 MR BUNDA: I am going to object to the characterizatior 11 of counsel of the Baxter and Fox study presetned to the 12 witness for his review. 13 BY MR DELL! BOVI: 14 Q Let me refer you. Dr Doll, to an article entitled: 15 "Occupational hazards in the PVC industry", written by William 16 Nicholson. You know Dr Nicholson? 17 A Yes, I do. v 18 Q In which he states at page 170: "Interestingly, an 19 cess c stonach carer vbs saai in the proportional mortality study of Baxter ad Fix." 20 The last sentence. Do 1 quote accurately from Dr Nicholson's 21 article? 22 A Yes. 23 MR BUNDA: What page was that? 24 MR DELLI BOVI: 170. 25 I l > j Tennyson & Company * Court Reporters London, Engtend 01144-12424164 UCC 073016 72 1 BY MR DELLI BOVI: 2 Q In addition to the Baxter and Fox article ;that you did 3 not review and the Chiazze article which you did not rely on, 4 you referred to a Swedish study and you forgot the name of the 5 author of that study? 6 A Is that Molina? 7 Q Xes. 8 A I specifically excluded that for .a number of reasons. 9 Q What I would like to ask you. Dr Doll, is'in your 10 paper that you wrote in 1988, you did refer to two studies done 11 in Sweden at page 66, the top of the right-hand column? 12 A Yes. 13 Q The Swedish study that you relied on that covered two 14 plants was done by Byren and others in 1976? 15 A Yes. 16 Q And that involved workers in plants producing vinyl 17 chloride and polyvinyl chloride? 18 A Yes. 19 Q It did not include PVC fabrication workers? 20 A No. 21 Q So for purposes of your article and the opinions you 22 have given here today, you have relied on a 1976 Swedish study 23 of vinyl chloride and PVC manufacturing employees, but not the 24 1981 Swedish study of PVC fabrication workers? 25 A I read the one on PVC fabrication workers end decided Tennyson & Company - Court Reporter* London, England 01144*12424164 UCC 073017 74 1 industry. 2 A That last one vas a study of the employees of the 3 factory, the plant in which Messrs Wallace and Dendinger worked. t 4 Q Have you reviewed that study? 5 A I have studied the report, yes. 6 Q And that was the report prepared by Dr Shindell? 7 A Yes. 8 Q Did you know of Dr Shindell before you saw his report? 9 A No. 10 Q Going back for a minute to Dr Chiazze, were you aware 11 that Dr Chiazze1s initial work was paid for by the Trade Industry 12 for the PVC manufacturers of the United States? 13 A I cannot recall that but if he says it, I am sure it 14 was. 15 Q And your suggestion with regard to the conclusions or 16 hypotheses that Dr Chiazze derived from his study, was that they i 17 should be further analysed* and were, and that further research 1 18 should be done? , 19 A Yes. 20 Q Are you aware of any efforts by the American PVC 21 industry to sponsor further studies of PVC fabrication employees 22 in the light of the results reported by Dr Chiazze in his 1981 23 work? 24 A 1 have no idea what they have done, 1 am not in touch 25 with the industry. Tannyton & Company * Court Reporter* London. England 0174402424164 UCC 073018 75 1 Q Was your `recommendation, however, that follow-up 2 studies be done? 3 A I think that would be a reasonable thing to do, yes 4 and Dr Shindell, of course, could be cited, 1 suppose, as one 5 such study. 6 Q Then let us talk about Dr Shindell's study. Do you hav<* 7 a copy of that with you, doctor? 8 A I could get it, yes. (Pause) Yes, I have. 9 Q I would like to direct your attention if I could to 10 Table II in Dr Shindell's study that appeas at page 12. Do you 11 have that in front of you, sir? 12 A Yes. 13 Q What is your understanding as to the job categories 14 in which Mr Wallace and Mr Dendinger were employed? 15 A My understanding is that they were employed in the 16 categories described there as inspection shipping - - no, 1 am 17 sorry, coating and finishing. ; 18 Q Your understanding is that both----- 19 A I am sorry, I think I may be wrong on this. I thought 20 one was inspecting, was he not? 21 Q Let me make a representation. 22 A Can you remind me? 23 Q It is my understanding that Mr Wallace was classified 24 as a coating finishing employee and Mr Dendinger was'classified 25 as an inspection shipping employee. Tennyson & Company Court Reporters London, England 01144*12424164 UCC 073019 76 1 A In other words I was right in both cases but for the 2 wrong reasons. 3 Q I suppose so. What I would like to do doctor, is to 4 have you contrast the Shindell study with the Chiazze study. 5 How would you classify this study that Dr Shindell did in terms 6 of epidemiologic categories? 7 A This is a cohort study and as such is the type of stud} 8 that one likes to carry out to test a hypothesis. 9 Q One of the hypotheses that Dr Chiazze proposed in his 10 1981 article was that there was an increase in the proportion 11 of total cancer deaths among white male PVC fabrication employees 12 A Yes. 13 Q So one of the follow-ups that you would have suggested 14 to confirm or disprove Dr Chiazze*s hypothesis was the cohort 15 study done by Dr Shindell? 16 A Yes. 17 Q What I would like to do. Dr Doll, is to have you look 18 at Table II and the total cancers reported in the coating finishing 19 and the inspection shipping categories, in which my clients 20 decedents worked. If we can take the coating finishing category 21 first in which Mr Wallace was employed and determine the total 22 number of cancers that would have been expected in a general 23 population, we could take that by adding the 1*4 expected 24 respiratory cancers and the 2.47 expected other cancers. Would 25 that be correct? Ttnnyaon Si Company * Court Reporters London, England 01144-12424164 ucc 073020 TT 1 A Yes. 2 Q Could we go off the record for just a minute, please? 3 (Whereupon there followed a discussion off the record) 4 BY MR DELL1 BOVI: 5 Q Dr Doll, referring to Table II in Dr Shindell's study 6 and the two categories of employees which Mr Dendinger and 7 Mr Wallace worked, there are data reported in both of respiratory 8 cancers and other cancers, correct? 3 A Yes. 10 Q And these are categories that were set up by Dr Shindell 11 for purposes of his analysis? 12 A Yes. 13 Q I would like to direct your attention to the exhibits 14 that we have on the easel which I will mark as Plaintiffs Exhibit 15 Doll 3. 1 would like, if you would, to refer to the respiratory 16 cancer deaths and the other cancer deaths in the job classifi- ! V I 17 cations in which Mr Wallace and Mr Dendinger were classified and | 18 tell me whether or not the figures that are on Exhibit 3 are [ 19 identical to those appearing in Dr Shindell's study? 20 A Yes, they are. 21 Q What I would like 22 A 1 have not checked the addition but I am assuming the 23 addition is correct. 24 Q I hope so. What I would like you to do. Dr -Doll, is 25 to do something Dr Shindell did not do in his study and that is Tennyon & Company Court Reporter* London, England 01144*12424164 UCC 073021 78 1 to determine in terms of total cancers in the job categories in 2 which Mr Wallace and Mr Dendinger were employed, the significancr 3 of the observed deaths, versus the expected deaths.: Would you % 4 be able to do that, sir? 5 A I would have to look at the tables of significance. 6 From my general experience I would guess the coating and finishing 7 one was not significant statistically, but the inspection and 8 shipping was, but that is a guess and 1 would have to look at 9 the table. You can doubtless tell me. 10 Q Let me go back to the findings that Dr Shindell came 11 to himself. With regard to the respiratory cancers among the 12 coating and finishing employees, Dr Shindell calculated the 13 expected deaths at 1.4, correct? 14 A Yes. 15 Q What does that indicate, doctor? 16 A That had the people in those particular sections of 17 the industry died at the same rate as the people of the same 18 ages in the United States as a whole, from respiratory cancer, 19 that 1.4 of them, if you can accept 0.4 of an individual, would 20 have died of respiratory cancer. 21 Q As opposed to the 1.4 expected deaths. Dr Shindell 22 reported actual deaths among employees at the plant where my 23 clients' decedents worked? 24 A Yes. 25 Q Did Dr Shindell determine that that number of observed Tennyson & Company Court Reporters London, England 01144-12424164 UCC 073022 7T 1 deaths versus the number of expected desths was statistically 2 significant? 3 A Yes, he said it was but when 1 looked it up in my .% 4 tables 1 found it was not but it is a quibble because it is 5 round about 5X probability and whether it is 4Z or 6Z is scientifi 6 cally of trivial importance. Actually, I make it nearer 6Z than 7 41. 8 Q And that means what, doctor? 9 A That means to have observed four or more deaths from 10 respiratory cancer in that particular group of people of those 11 ages over that period in the United States would have turned up 12 only about once in twenty such groups that you looked at. 13 Q Next I would like to direct you to the inspection and 14 shipping category of employees in which Mr Dendinger worked and 15 to the other cancers. According to Dr Shindell's method of 16 classification, would those other cancers include the colon 17 cancer from which Mr Dendinger died? 18 A Yes. j 19 Q In that category. Dr Doll, one would have expected, 20 assuming the death rate from these other cancers among inspection 21 shipping employees at Chrysler, was the same as that among a 22 comparable general population, 1.95? 23 A Yes. 24 Q And in fact at Chrysler there were five employees who 25 died of cancers other than respiratory cancer? if Tennyson & Company - Court Reporters London, England 01144-12424164 UCC 073023 80 1 A Yes. 2 Q Is that number again. Dr Doll, statistically signifi 3 cant? 4A This time I have no difficulty in agreeing with 5 Dr Shindell. 6 Q In terms of testing Dr Chiazze's 1981 hypothesis of 7 an increase in overall cancers among PVC fabrication employees, 8 is it fair to total these four categories of employees to arrive 9 at sum total figures? 10 A Mo. 11 Q Why is that, doctor? 12 A Because you have subscribed the population and picked 13 out some groups with higher mortalities than other groups. You 14 have left out the production and maintenance group which did not 15 show such an excess. It showed, I think, 4 cancers against 3.72 16 expected and you left out the management and clerical group j 17 which showed no cancers against 1.79 expected and when you sub- ' ! 18 divide and look at a number of separate groups, then inevitably j 19 you are going to find some with statistically significant 20 excesses. Had the prior hypothesis of Dr Chiazze been that 21 people in the coating finishing and inspection shipping groups 22 had a higher than expected mortality from cancer, then that would 23 be a fair thing to do, but it was not. It was that all the 24 employees of the PVC fabrication industry had an excess and, 25 therefore, you have to look at the total. Again, you get'your - Tennyson & Company - Court Reporters London, England 01144-12424164 UCC 073024 81 1 self into a situation in which you create another hypothesis 2 when you find an excess in some subdivisions. You find now an 3 excess in the coating finishing and inspection shipping divisions 4 and that constitutes a new hypothesis which will have to be tested 5 by further experience of those workers. I would like to carry 6 that a little further because in testing a hypothesis I think 7 it is important that you take into account the area in which the 8 people were working. Dr Chlazze's hypothesis was based on the 9 workers in, I think, seventeen plants, but my memory, may be 10 fallible about that, scattered throughout the United States and 11 he, therefore, very properly or reasonably took the whole of the 12 United States mortality experience as a standard to compare with 13 it. If, however, you are looking at a plant in Ohio, then you 14 need to see what the mortality from cancer is in Ohio, how that 15 compares with the rest of the United States. I have not got the 16 figures for that, it is a highly industrialised State or part 17 of it, I believe is and I would expect the expected mortality 18 from cancer to be higher than is estimated from the national 19 United States rates. 20 Q To a significant degree? 21 A Yes. 22 Q Have you been presented with data for Ohio by any of 23 the PVC manufacturers? 24 A No. 25 Q Did you consider the cancer deaths reported at* the Tennyson & Company - Court Reporters London, England 01144-12424164 UCC 073025 82 1 Chrysler facility by Dr Shindell in coming to the opinions that 2 you have suggested today? 3 A Dr Shindell*s paper was not available at the time 1 - 4 made my review. 5 Q When did you first see Dr Shindell*s paper? 6 A About two weeks ago, one week, ten days ago. 7 Q In terms of Mr Dendinger and Mr Wallace, I take it you 8 do not have an opinion as to the cause of either gentleman's 9 cancer? 10 A No. 11 Q Were you provided with any information about their age, 12 at the time of death, their diet, their family history or known 13 history of cancer, their inhallation of tobacco smoke, if any, 14 or their use of alcohol, if any? 15 A Yes, some limited data. Certainly precise data for 16 age and some details for the other things that you mention but j 17 none of them in fact are relevant or would be regarded as `j 18 relevant to the aetiology of their conditions. When I say that, 19 I do not mean diet is not relevant to theaetiology of cancer of 20 the colon, all 1 mean is the sort of information that could be 21 given about the individual would not affect my assessment 22 because one cannot really assess an individual's diets sufficiently 23 precisely to be of any value on deciding if it is a cause of his 24 cancer. 25 Q In terms of your opinions that you have expressed today. Tennyson & Company - Court Reporters London, England 01144*12424164 UCC 073026 ------------------------- --------------------------------------------------------------------------------------------------- 83" 1 you have not relied pn the Shindell study at the Chrysler plant, 2 the Chiazze study of FVC fabrication employees, the Molina study 3 of PVC fabrication employees, is that correct? 4 A No. I have certainly taken them all into full account 5 and weighed the evidence that they have produced before 6 expressing my opinion which is an opinion based on all the data 7 1 have seen including the data which you have provided me with 8 and which 1 was provided with in the last few months. 9 Q What determined whether or not a particular study made 10 your list of references at the conclusion of your paper? 11 A Whether it was relevant to the conclusions which I 12 reached in it. I did not list quite a number of studies which 13 I read, including the Chiazze study because I did not think it 14 was relevant to the conclusion which I reached. 15 Q Your belief then was that Chiazze was not relevant? 16 A I thought that Chiazze*s study was not helping in any v 17 way assess what the effects of vinyl chloride were. ! \ 18 Q That Molina was not relevant? j 19 A Molina was definitely not relevant. 20 Q And Shindell was not relevant? 21 A Shindell I only recently took into account in expressing 22 my opinion today. 23 Q The report with the review that you authored .and 24 appeared in the Scandinavian journal, was commissioned by the 25 Manufacturing Chemists Association? Tennyson & Company Court Reporters London, England 01144-12424164 UCC 073027 84 1 A It depends what you mean by "commissioned". If by 2 "commissioned", you mean was I paid to do it, the answer is no. 3 If by "commissioned" you mean was I asked to do it in an 4 honorary capacity, the answer is yes. I said I was glad to do 5 it, it was an interesting and important subject and I would do 6 it on the understanding they made a contribution to a charity 7 which I named. So, depending what you mean by "commissioned", 8 there is my answer. 9 Q And, if you do not mind my inquiry, could you tell me 10 the amount of the contribution KCA agreed to pay? 11 A Oh, I will have to look it up. It might have been 12 $10,000, 7,000, It was not paid to me, it was paid to the 13 charity. 14 Q Can you tell me for certain whether or not the study 15 was commissioned before or after 1985? 16 A No, I cannot. I think it was before, probably. I knov 17 it was about two years before I could start on it. I did the 18 work in 1986. I would guess it was 1984 I was asked to do it i i 19 but it might have been 1985. 20 Q Could you tell me, doctor, precisely what assignment 21 you received from the MCA? 22 A 1 cannot remember the exact wording. It was about 23 three lines to review the evidence on the effect of vinyl 24 chloride on man with specific reference to whether there was any 25 increase of any cancer other than angiosarcoma of the liver. Tannyaon & Company - Court Reporters London, England 01144*12424164 UCC 073028 85 1 I think that was the way it was put. 2 Q Do you know whether or not that study was sought by 3 the MCA after Mr Dendinger and Mr Wallace filed their litigation' 4 A I have no idea. I do not know when they filed it. 5 Q Of the four major studies that your article reviews, 6 three were - at least at the time you wrote the article - un 7 published?" 8 A Yes. They are published now. 9 Q Are all four of the studies that you have reviewed 10 published? 11 A No, the American study, to my knowledge, has not been 12 published yet although I believe it is available to anyone who 13 asks for it. 14 Q How did the United States study come to your knowledge* 15 A It came to my knowledge because when I started doing 16 the review I was dealing with a lot of separate papers about 17 populations exposed to vinyl chloride in the United States and 1 i 18 there was one of them done by an American organization, I forget j 19 the name. Equitable and Environmental Health Inc., that covered 20 a substantial number of plants and there was a follow up study 21 to this by a man beginning with C--22 Q Cooper? 23 A Cooper, and I wondered whether the individual studies 24 reported by other authors were included in these two studies. 25 Clearly, in a review you do not want to add in the same amount Tennyson & Company - Court Reporters London, England 01144*12424164 UCC 073029 1 of data three or four tines as reported by different people. 2 It is important you only include one set of data on one occasion, 3 so I enquired of the chemical industry through the Imperial 4 Chemical Industries in England, whether I could be told whether 5 these studies of Cooper and Tabershaw and Gaffey covered, the. 6 other studies and I was told that they did and then I was told 7 also that another study was being carried out and I said that 8 a follow up study was being carried out and I said it is silly 9 for me to give an opinion until I had seen the follow up study, 10 so X waited till I had seen the follow up study. I made the 11 same inquiries in England. 1 had a report of Fox and Collier 12 of the British Industry and I wrote to the Health and Safety 13 Executive in England to ask if they were doing any further 14 studies and they told me there was this government study that 15 covered the whole industry in England and I said: "I must wait 16 and have the results of both these studies before I can give an j 17 opinion." Could we go off the record for a moment while the i 18 refreshments come in? j 19 MR DELLI BOVI: Yes, why don't we go off the record. 20 (Whereupon there followed a short adjournment) 21 BY MR DELLI BOVI: 22 Q Dr Doll, I am going to hand you what 1 have marked as 23 Plaintiffs Exhibit 4. Would you review this document and tell 24 me whether or not this is a copy of the study that is.cited in 25 your review that was prepared from the Chemical Manufacturers Tennyson & Company - Court Reporters London, England 01144*12424164 UCC 073030 87 1 Association. (Document handed to the witness) 2 A Yes, that is the one. 3 Q To your knowledge, that study remains unpublished? * 4 A Yes. What I am saying by that is I do not know if it 5 is published. 6 Q One of the other studies referred to in your reference; 7 as reference 16 is a 1978 study by Equitable Environmental 8 Health entitled: "Epidemiological Study of Vinyl Chloride 9 Workers: Final Report to Manufacturing Chemists Association." 10 Do you have a copy of that report with you this afternoon? 11 A No, I do not have a copy of that with me. This was 12 subsumed in this later report and it is a long time since I read 13 it. It is not relevant to my review. 14 Q So, among the references that you cited in your review 15 are references that are not relevant to it? 16 A I cited and gave reasons why I have not incldued them, 1 17 saying the data in it has Seen subsumed in the later one, but 18 I cited it because otherwise people might have wondered why 1 ' i ; 19 did not mention it. 20 Q Where did you obtain the 1978 Equitable Environmental 21 Health Report? 22 A I cannot Temember now. I am guessing, probably from 23 Imperial Chemical Industries or I might have had it from Cooper 24 himself. I think that was the one that Cooper published, was 25 it not? Tennyson & Company - Court Reporters London, England 01144-12424164 UCC 073031 88 1 Q Was that study, to your knowledge, ever published? 2 A Not to my knowledge, no. 3 Q Imperial Chemical Industries-- m 4 A Wait a minute. We have got Cooper as a separate one, 5 have we not? 6 Q Yes. 7 A Nov, this one, I think that was a preliminary report 8 to Cooper so Cooper would be regarded as the publication of 9 number 16. I think that Is right. So, the answer, therefore, 10 would be yes it was published if I am correct, but I really have 11 to check to make sure 1 am being correct on that. Earlier 12 observations, that is right. Yes, yes. Without going back and 13 looking at the data, my recollection is that 12 was the publi 14 cation in effect of 16, but I would not want to swear to it 15 without checking. 16 Q Dr Doll, can you tell us what a carcinogen is? 17 A I wish I could. v What one means by a carcinogen is i 18 any agent which will cause cancer in any animal if that animal 19 is exposed to it in any conditions the experimenter likes to 20 think. An agent capable of causing cancer in some circumstances. 21 Q Is vinyl chloride a carcinogen? 22 A Yes. 23 Q What is a human carcinogen? 24 A A human carcinogen is a carcinogen shown to.cause cance r 25 in humans. Tennyson A Company - Court Raportars London, England 01144-12424164 UCC 073032 B9 1 Q Is vinyl chloride a human carcinogen? 2 A Yes. 3 Q What is a mutagen? % 4 A That is very much more difficult to define because it 5 has a very wide connotation of meanings given to it by different 6 workers. Essentially, it is something which damages the DNA in 7 a cell, causes the DNA which is the material that holds all the 8 codes as to how that cell is to operate, which causes that DNA 9 to be altered in some say. 10 Q Is vinyl chloride a mutagen? 11 A Yes. 12 Q Is it your understanding that prior to the 1970 work 13 of Professor Viola, there were a large numberof studies done 14 concerning the acute, the sub-acute and the chronic health effects 15 on humans of over exposure to vinyl chloride? 16 A Yes. 17 Q Could you outline for us some of the acute, the sub 18 acute and chronic effects of exposure to vinyl chloride that were 19 reported prior to 1970? 20 A The first effect, of course, is just unconsciousness, 21 if it is a sufficiently high dose of the gas, but once the con 22 centration to which individuals are exposed is kept down to 23 lower levels, then it is found that chronic exposure at these 24 lower levels would cause some damage to the liver, they would 25 cause damage to the terminal phalanges, the boneB in the fingers. Tannyaon & Company - Court Reporters London, England 01144-12424164 UCC 073033 -------- -- 1 1 -------- , 90 1 I forget the technical term - aci&-ostiolytis. Also that it woulcj 2 have some effect on the circulatory system* producing symptoms 3 that are known medically as Raynaud phenomena. * 4 principal effects I can recall* Those are the 5 Q Do you recall whether or not much of the work done .intc 6 the health effects of exposure to vinyl chloride prior to 1970 7 was done in' the Eastern European nations? 8 A I know of one report from the Soviet Union, but no, 9 I am afraid I cannot answer that. 10 MR BUNDA: I am going to interpose an objection that 11 the cross examination is going beyond the scope of the 12 direct examination. 13 BY MR DELLI BOVI: 14 Q Have you looked into the history of the medical and 15 scientific articles dealing with the toxicity of vinyl chloride 16 as part of your assignment for the CMA? 17 A Only levels beloW those which produce the so-called I 18 vinyl chloride syndrome which I did not think was necessary for 19 me to investigate because that was well established and as far 20 as I knew was * agreed by everybody and not controversial but 21 I certainly looked to see if there were any other long term effects 22 on individuals which would show up in mortality rates from 23 diseases other than cancer. 24 Q Is it your understanding that evidence of the carcino- 25 * gencity of vinyl chloride was first reported by Professor Viola Tennyson & Company- Court Reporters London, Enplsnd 01144-12424164 UCC 073034 91 1 in 1970? 2 A Yes. 3 MR BUNDA: I would like to interpose a continuing 4 objection on the basis the cross examination is going beyond 5 the scope of direct examination. 6 BY MR BELLI BOVI: 7 Q I would like to hand you, doctor, a series of medical 8 journal articles and have you identify them for me, if you would. 9 Can we go off the record for just a second while I find them. 10 Never mind, I have them. 11 MR BUNDA: I would like to go off the record for a 12 second 13 (Whereupon there followed a discussion off the record) 14 MR BUNDA: 1 am also going to object to the introductiojn 15 of these exhibits or the showing the witness these exhibits 16 in their present form since they have stickers all over them; 17 and I think that that- is prejudicial. If you have any clean 18 *i copies I have no objection to the doctor being questioned 19 about those. 20 MR DELLI BOVI: I have no clean copies. 21 MR BUNDA: Then I object. 22 BY MR DELLI BOVI: 23 Q Doctor, I show you Exhibit 5. You can feel free to 24 ignore all stickers on there other than those that refer to your 25 testimony. (Document handed to the witness) Tannyson & Company - Court Reporters London, England 01144-12424164 UCC 073035 92 1 MR BUNDA:. Objection, I move to strike. 2 BY MR DELLI BOVI: 3 Q Have you seen that document before in that form or any 4 other form? 5 A Yes I believe this is one of the documents 1 vas 6 provided when I was asked if 1 would give evidence in this case. 7 I had not seen it before then. 8 Q The first time you saw Dr Viola's 1970 publication in 9 the Italian medical journal was in 1985? 10 A No, I said 1988, just a week or so ago. I had not 11 thought it necessary to look for this article as I knew, of 12 course. Dr Viola's publication of 1971 and it seemed to me that 13 subsumed the earlier evidence and I did not think it necessary 14 to go to the preliminary report in 1970. 15 Q Well, Dr Doll, you had to have seen that document priori 16 to 1988. 17 A Did I? Yes. 18 MR BUNDA: Objection. Argumentative. i i i 19 BY MR DELLI BOVI: 20 Q 21 year? Is it your testimony you first saw that article this 22 A I am confused slightly. I think there is an article 23 by Viola of 1971. 24 Q That Is correct, in Cancer Research. 25 A As far as I can recall I have only read Viola's article Tennyson a Company - Court Reporters London, England 01144-12424164 UCC 073036 93 1 of 1971 before this-last few weeks* I saw no reason for looking 2 up Viola's article of 1970 and I am not aware of having seen it 3 before. 4 % MR BUNDA: 1 am also going to Interpose an objection 5 on the basis there has been no other occasion that that- 6 document is in the form in which it appeared in the Italian 7 journals. My understanding is that it is a translation and 8 on that basis I believe the questions are improper because 9 they infer that that is a copy of the form in which the 10 articles were published and I think that is not borne out 11 by the facts. So I do not have to continue to object, I 12 believe there will be a second article following the 13 objections which I made with regard to the stickers and with 14 regard to the fact it is a translation, also applies to that 15 article, also authored by Dr Viola. 16 BY MR DELLI BOVI: V 17 Q I would like to refer you to an article you co- authored 18 in 1985. Would you take a look at that and indicate whether your; 19 first reference in that 1985 work was to Dr Viola's 1970 publi 20 cation, in the medical journal article. (Document handed to the 21 witness) 22 A Yes, it was. 23 Q So, you were aware as early as 1985 of Dr Viola's 1970 24 publication? 25 # A Oh, I have been aware of it .earlier than that but as Tennyson & Company - Court Reporters London, England 01144-12434164 UCC 073037 1 I said, I did not regard it as necessary to read it, as Dr Viola 2 published a paper In 1971 which was the definitive results of 3 his study and I based all my conclusions on Viola's 1971 paper. m 4 This was a paper Jointly by myself and three other colleagues 5 and they doubtless thought if you are referring to Viola it was 6 only reasonable to give the first reference to Viola, but the 7 one that I read and studied is the 1971 one. 8 Q When were you first aware whether or not you read of 9 the findings reported by Dr Viola in 1970? 10 A I cannot recall that 1 was aware of them reported in 11 1970. I was aware of them reported in 1971 - - oh, I suppose 12 in 1975. When did I first start getting interested in vinyl 13 chloride? When I gave a paper, joined in a discussion at the 14 New York Academy of Sciences which must have been in the mid 1970js. 15 I cannot remember the exact year, but I would say 1974 or 1975 16 I was aware of the 1971 paper. 17 Q What about the JP&70 paper? 18 A It must have -- it was drawn to my attention when I 19 read the 1971 paper because there was the reference presumably 20 in it but I cannot recall having seen it until this last week 21 or two. 22 Q Would you take a look at Professor Viola's 1971 documeri 23 and see if there is in fact any reference to his 1971 publication] 24 (Document handed to the witness) 25 A No, there is a reference to his 1969 one, which I had Tannyaon & Company Court Reporters London, England 01144-12424164 UCC 073038 95 1 heard of, of course. 2 Q Have you ever reviewed that publication* sir? 3 A No* because 1 have worked with Maiton! who continued 4 his work aiid Maltonl told me all about the work and 1 had, 5 therefore, known about this work, Viola's since the middle 1970s, 6 Q Do you know whether Dr Viola in his 1969 presentation 7 at the International Cancer Congress in Tokyo discussed the 8 subject of carcinogenicity of vinyl chloride? 9 A I cannot answer that with certainty. My belief is that 10 he reported it in 1969, That is my understanding but I could 11 not be held to that. 12 Q Whether or not it was reported in 1969, certainly by 13 1970 Dr Viola had authored a publication in one of the Italian 14 medical journal articles, dealing with the carcinogenicity of 15 vinyl chloride in animals? 16 A I dare say. I 17 Q You, however, wee not aware of either his 1969 or his 18 1970 publication until some years later? ! 19 A I was not aware of it until after the occurrence of 20 the two or three cases of angiosarcoma in the Goodyear works 21 in the early 1970s. 22 Q If the Goodyear angiosarcoma deaths were announced in 23 1974, then you would not have been aware of Dr Viola's 1970 paper 24 until that time? 25 A That is right, yes. Tennyson it Company - Court Reporters London, England 01144-12424164 UCC 073039 96 1 Q Is Cancer Research a European publication? 2 A No. 3 Q Where is that published? 4 A The United States. 5 Q Are you aware of any evidence of an effort by the 6 polyvinyl chloride industry in the United States to hide 7 Or Viola's 1970 publication from its customers, from the United 8 States government and from the general public? 9 A No. 10 Q Would you regard such an effort, if it occurred, as 11 evidencing a lack of corporate responsibility on the part of 12 vinyl chloride and polyvinyl chloride manufacturers ----- 13 MR BUNDA: Objection. Dr Doll, wait a second, let me 14 interpose an objection on the basis it is speculative and 15 is not based on any facts which are properly in evidence. 16 You can go ahead and answer the question if you recall what 17 it is. .\, 18 BY THE WITNESS: 19 A No, it is too hypothetical for me to give any answer 20 to. 21 BY MR DELLI BOVI: 22 Q Then, Dr Doll, I would like to make the question some 23 what more concrete. Would you look at Plaintiffs1 Exhibit Doll 24 6, please and tell me whether you have seen this document or 25 reviewed this document before? (Document handed to the witness) Tennyson A Company Court Reporter* London, England 01144-12424164 UCC 073040 w 1 MR BUNDA: Again, I am interposing an objection on the 2 basis it goes beyond the scope of the cross examination and 3 further more, it is irrelevant. 4 BY THE WITNESS: 5 A I am very happy to answer it because I have never seen 6 it before. 7 BY MR DELL! BOVI: 8 Q 1 would like you also to take a look and tell me whethc r 9 you have seen, prior to today. Plaintiffs* Exhibit 7 which is 10 entitled: "Cancerogenic Effect of Vinyl Chloride, P.L.Viola n (Regina Elene Institute for Cancer Research) Rome, Italy, 12 presented at the Tenth International Cancer Congress, Houston, 13 Texas. May 22-29, 1970". 14 MR BUNDA: Can I see that please? (Document handed 15 to counsel) Again I am going to interpose an objection on 16 the basis that this document contains multiple stickers and 17 is prejudicial in its presentation. Furthermore, it appears 18 to be a summary and it is difficult to determine where it 19 comes from. So, I object on the basis of authenticity as 20 well. 21 BY MR DELLI BOVI: 22 Q Have you seen Plaintiffs* Exhibit 7 before today? 23 (Document handed to the witness) 24 A Well, 1 find that difficult to answer because I attends 25 this conference, in fact I gave the opening lecture 'at it and Tennyson & Company Court Reporters London, England 01144*12424164 UCC 073041 98 1 it is possible this Is a photocopy of an abstract, in which case 2 I might have seen it, but 1 cannot recall having seen it and my 3 interest in vinyl chloride as a carcinogen only arose in 1974 t 4 or so when*I heard about the angiosarcoma cases, so whether I 5 saw it or not I do not know. It is possible 1 did, but it 6 certainly made no impact on me if I saw it. 7 Q You indicated earlier that you had not seen Plaintiffs' 8 Exhibit Doll 6 before. Is that correct? (Document handed to 9 the witness) 10 A 1 indicated that. 1 would like to read it again just 11 to make quite sure that I am not misleading you. (Pause) No, 12 I am not aware of ever having seen that before. 13 Q You were a professor of epidemiology at Oxford College, 14 1970, 1971, 1972, 1973 and during those years you had not seen 15 Dr Viola's 1970 article. It had not come to your attention 16 during those years? 17 A I was actaully a professor of clinical medicine techni-' 18 cally but my research was all in the field of epidemiology. I i 19 was au fait as I taught with the cancer research work throughout 20 the world. I discussed many carcinogens with many cancer research 21 workers and I can never recall anybody mentioning vinyl chloride 22 as a carcinogen at all until after the angiosarcoma cases occurred 23 in the Goodyear works. 24 Q In 1974? 25 A In 1974, yes. I certainly would not claim to have been Tennyson A Company Court Reporters London, England 01144-12424164 ucc 073042 99 1 completely up to date and obviously I was not. but there were 2 a lot of things going on and certainly in the cancer research 3 world generally, vinyl chloride was not being discussed as a 4 potential hazard. 5 Q Please do not infer from my question that 1 am finding 6 any fault at all in that fact but the fact is that you were an 7 expert in epidemiology in the early 1970s and prior to 1974 none 8 of Dr Viola's work or Dr Maltoni's work had come to your attenticn? 9 A That is true, yes. Of course* there were .many', many 10 animal carcinogens which had not been drawn to my attention at 11 the same time. 12 Q Do you feel. Dr Doll, as a physician, that when a man 13 ufacturer of a product learns of studies that indicate a potential 14 cancerogenic problem with that product, that they have a duty 15 to disclose that information to their workers and to their 16 customers? 17 MR BUNDA: Objection. I am going to interpose an ] 18 objection on the basis it is speculative, it is a vague 19 question, it improperly states the facts of the situation 20 and further more, is irrelevant to this particular case. 21 BY THE WITNESS: 22 A My answer to the question would be I cannot give an 23 answer to it because it depends upon the situation. I am very 24 much opposed to frightening people unnecessarily. If you asked 25 me whether on the basis of such findings, inquiries should be Tennyaon & Company Court Reporters London. England 01144*12424164 UCC 073043 100 1 made as to whether there were any hazards to humans but I would 2 say unhesitatingly yes, but the question of disclosure is always 3 a very difficult one. There are so many things which can cause 4 cancer In certain circumstances, and one has to, as a research 5 worker, use your judgment as to what is proper information and 6 what is scaremongering and 1 would not feel that I could pass 7 judgment on'actions taken many years ago on the basis of a 6 totality of evidence of which I am not wholly aware. 9 BY MR DELLI BOVI: 10 Q Do you regard Dr Maltoni's 1970 and 1971 publications 11 which has been marked as Doll Exhibits 5,7 and which I will mark 12 as Doll Exhihit 8----- 13 MR BUNDA: Hang on. Did you miss-state yourself. You 14 mentioned Dr Maltoni. Did you mean Dr Viola? 15 MR DELLI BOVI: Dr Viola. 16 MR BUNDA: What is the exhibit number? 17 MR DELLI BOVI: 5, 7 and 8. j 18 MR BUNDA: Again I object to the nutnerocity of the 19 exhibit numbers. 20 BY MR DELLI BOVI: 21 Q Do you regard those documents. Dr Doll, as documents 22 calling into serious question the carcinogericity of vinyl chloride. 23 (Documents handed to the witness) 24 A I regard the one in 2 971 in Cancer Research .as so doing. 25 The others I regard as preliminary reports and I think one would Tennyson & Company - Court Reporters London. England 01144-12424164 Ucc 073044 101 1 be unwise to draw any conclusions, any important conclusions fron 2 them but the paper in 1971 by Viola, Bigotti and Caputo is 3 certainly an important paper to which attention should be paid. 4 Q Is your understanding that Dr Viola, at the time he 5 authored these papers, was employed by one of the European PVC 6 manufacturers? 7 A I have no idea who he was employed by. I know 8 Dr Maltoni personally but I do not know Dr Viola, I have never 9 met him. 10 Q You indicate in your 1985 publication: "The idea that 11 vinyl chloride might cause cancer was first suggested by Viola 12 in 1970 as a result of experiments in rats". Correct? 13 A Yes, I said that but clearly it is wrong because he 14 reported it in 1969, verbally, did he not, at the Houston 15 conference. 16 MR BUNDAt I am going to object and move to strike. 17 1 think the Houston conference is 1970. 18 THE WITNESS: Ah, 1970. 19 BY MR DELLI BOVI: I j ! i 20 Q Tokyo was 1969? 21 A 1966. I do not know what conference that was. The 22 cancer conference was Tokyo, 1966. 23 Q The 16th Congress on Occupational Health. 24 A Oh, I did not know anything about that conference. 25 Q You indicated earlier that you were not aware of any Tennyson & Compsny - Court Reporters London, England 01144-12424164 UCC 073045 102 1 efforts by any PVC manufacturers in the United States to keep 2 the 1970 findings of Dr Viola from being published in the United 3 States? 4 A Yes. 5 Q Is it your belief. Dr Doll, that the PVC manufacturing 6 industry after the publications of Dr Viola in 1970 and 1971, 7 had an obligation to disclose Dr Viola's findings to their 8 employees and to their customers? 9 MR BUNDA: Objection, I think it calls for speculation, 10 it is a vague question, it is over broad and it is irrelevar t 11 to this case and mischaracterizes the information which is 12 in evidence and the status of the situation which existed 13 in 1970. 14 BY THE WITNESS: 15 A I do not think I could give an answer about what 16 happened at that time. I was not aware of what was going oh and i 17 it would be too speculative. I \ 18 BY MR DELLI BOVI: ; 19 Q Dr Doll, I am not asking you to tell me or to tell this 20 jury what happened. What I am asking you as a physician specia 21 lising in epidemiology, whether, based on the 1970 and 1971 22 studies of Viola, the PVC industry had a duty to disclose those 23 findings to its customers and to its employees? 24 A I cannot answer that question because I am a scientist, 25 not a politician and I spend my time trying to decide what data Tannyaon & Company - Court Reporters London. England 01144*12424164 UCC 073046 io: 1 means. I do not tell people what they should do and I cannot 2 express an opinion on what people should have done or what people 3 should do now.. It is not my line. ** 4 Q You do not* in your capacity here at Oxford* advise 5 Industry or the Government on whether they should or should not 6 disclose particular epidemiological data? 7 A No* I do not think so. I am trying to think if I do. 8 I just publish my results in the scientific press and I think 9 that is the responsibility of the scientist. Then* 'other people 10 have to decide what they do about it. I remember when we first 11 discovered that smoking caused cancer of the lung* we were always 12 being asked what the Government should be doing about it and we 13 said: ''That is nothing to do with us." It took them seven years 14 to tell the public that smoking caused cancer of the lung and 15 I did not express an opinion on that. 16 Q Did you feel, based upon the initial results of your I 17 studies, that the public had a right to know what you found out? j 18 A I do not feel things - - well, that is not true, I 19 obviously do as a human being, but I try not to feel anything 20 on a scientific matter as that can prejudice my scientific judg 21 ment as to what the cause of disease is. I try to keep quite 22 separate from that field. I try to do work to find out what 23 causes disease* publish it openly and then it is for others to 24 decide what should be done* not for me. 25 Q I would like to read you an excerpt from Plaintiffs' Tennyson 8t Company Court Reporters London, England 01144-12424164 UCC 073047 104 1 Doll Exhibit 6. I am going to represent/Jou that this was an 2 internal memorandum prepared by R.N. Field of Union Carbide, as 3 the result of a meeting of the Occupational Health Committee of % 4 the Manufacturing Chemists Associations. The date of the memor 5 andum is November 23v 1971, "Publishing of Dr Viola's work In 6 the United States could lead to serious problems w'ith regard to 7 the vinyl chloride monomer and resin industry. These are as e follows:- 1) The Delaney amendment bans the use of any material 9 in food that can cause cancer. 2) A law exists in Pennsylvania 10 banning carcinogens from the air i.e. the allowable threshold 11 limit is zero. 3) The present political climate in the United 12 States is such that a campaign by Mr R. Nathan and others could 13 force an industrial upheaval, via new laws for strict interpre 14 tation of the pollution and occupational health laws." Did the 15 CMA, when they furnished you with materials for you to review 16 in connection with your 1988 review in the Scandinavian medical 17 journal, ever furnish you with a copy of that memorandum, sir? 18 A No. 19 Q Are you aware of any efforts by the polyvinyl chloride 20 industry between 1970 and 1974 to make publicly known or to make 21 known to their customers or to make known to their employees, 22 the findings of Dr Viola? 23 A No. 24 Q Are you aware of any efforts by the polyvinyl chloride 25 industry in the United States between 1970 and 1974 to conduct Tennyson & Company Court Reporters London, England 01144-12424164 UCC 073048 TBn 1 epidemiological research of PVC fabrication employees, following 2 the findings of Dr Viola. 3 MR BUNDA: I am going to interpose an objection to the 4 whole' line of questioning as I have done before* on the 5 basis that it is irrelevant, I am also going to object on 6 the basis that there is no foundation having been laid that 7 this witness has any knowledge about this area of inquiry 8 at all and I move to strike the whole line of questioning. 9 BY THE WITNESS: 10 A I can answer it very simply, I do not know anything 11 between 1970 and 1988, I am just not aware of what the American 12 industry has been doing apart from what is published. 13 BY MR DELLI BOVI: 14 Q Dr Doll, you presented a discussion paper to the New 15 York Academy of Sciences in 1975, did you not, at a conference 16 specifically held to discuss the carcinogenicity of vinyl chloride?* 17 A Yes. I think my paper was a summing -up, was it not . 18 A conclusion to the discussions. 19 Q 1 am going to hand you what I will mark as Plaintiffs* 20 Exhibit Doll 8. Could you identify that document, please, sir? 21 (Document handed to the witness) 22 A Yes. This is a report of my discussion and my contri 23 bution to the discussion. 24 Q That was at a conference discussing the carcinogenicity 25 of vinyl chloride approximately a year after the public ahnounce- Tannyaon & Company - Court Raportar* London, England 01144-12424164 UCC 073049 TW 1 ment of the Goodrich angiosarcoma deaths? 2 A I cannot remember the whole discussion. Certainly 3 vinyl chloride was part of it but I do not remember whether 4 there were other things discussed or not. 1 have a very poor 5 memory of the discussions. 1 only remember that in the report 6 of it 1 was made to say something which I did not say but that 7 is another matter. 8 Q Sure, and that particular point had nothing to do with 9 vinyl chloride? 10 A Not that point, no. 11 Q In fact, that point is corrected in that exhibit? 12 A Yes. 13 Q That exhibit reflected your presentation in 1975 and 14 does so accurately? 15 A Yes. 16 Q Is it your opinion that for any human carcinogen, in 17 cluding vinyl chloride, there is a safe level of exposure at 18 which no potential carcinogenic effects will occur? | i 19 A That is something I wish I could answer. I really have 20 not got an opinion on that. In cancer research we work on the 21 assumption that unless there are strong reasons otherwise, we 22 postulate that an effect is produced proportional to dose down 23 to vanishingly small levels but whether this is so or not is a 24 matter of great debate and which we really have no firm scientific 25 evidence one way or another. We act oh the assumption in*the Tennyson & Company Court Reporters London. England 01144-12424164 UCC 073050 107 1 same way as we are acting on the assumption now that other people's 2 tobacco smoke In a room will cause a risk to the peqple who are 3 not smoking, but the scientific proof that this is 50 is such 4 that I really have not got an opinion. What I have is a working 5 rule, but not an opinion. 6 Q What is your working rule? 7 A The working rule is to assume that there is an effect 8 proportional to dose down to vanishingly low levels, given that 9 the material is a mutagen. If it is not a mutagen, then my 10 working rule would be that is probably not the case and there 11 would be a threshold below which it had no effect. 12 Q Vinyl chloride is a mutagen? 13 A Yes. 14 Q Therefore, your working rule is what? 15 A My working rule is that you would assume there was an 16 effect proportional to dose down to vanishingly small levels. 17 A vanishingly small effect but an effect. 18 Q A vanishingly small effect with regard to the general 19 population, exposed, but a very--- 20 A Yes. 21 Q But a very real effect for that person who develops 22 the cancer? 23 MR BUNDA: Objection, calls for speculation. You can 24 go ahead and answer. 25 > Tannyaon & Company - Court Reporters London, England 01144-12424164 UCC 073051 ToTi 1 BY THE WITNESS: 2 A Yes, this is true, but I believe society has to accept 3 that there is such a thing as a negligible risk, otherwise 4 society is not possible to run, it becomes socially Impracticable 5 Q Let us have a look at vinyl chloride in this concept 6 of no safe level. You are aware, are you not - - let me back' 7 up one step. There are many types of cancer? 8 A Yes. 9 Q One of which is angiosarcoma of the liver? 10 A Yes. 11 Q Angiosarcoma of the liver is an exceedingly rare cancel ? 12 A Yes. 13 Q And occurs approximately to one person out of every 14 10m or 20m? 15 A Approximately once to every 10m each year. That is, 16 once to every 10m in a population in a year, yes. 17 Q You are aware of studies, are you not, postulating i i 18 increased risk of cancer from vinyl chloride at exposure levels 19 in the parts per billion? 20 A No. Oh, I am aware of some evidence that there may 21 have been some cases produced in the surroundings of some 22 factories in New York State where the concentrations to which 23 people were exposed were of the order of parts per billion. 24 -Whether they really did cause cancer or not is difficult to say. 25 What I have said and my policy in interpreting such <iata and. Tennyson & Company Court Reporters Condon. England 01144-12424164 ^CC013052 109 1 of course, this is coming up at the present moment in regard to 2 clusters of leukaemia in regard to nuclear installations, first 3 of all you have to decide is there a greater instance of this 4 particular' type of cancer in that neighbourhood. If you come 5 to the conclusion there is a greater one than it would be 6 reasonable to expect, you then have to say, well, what could it 7 be due to and it is very easy to jump to a conclusion that it 8 is due to a particular factory or a particular amount of waste 9 that is being released, environmental pollution, just on* the 10 grounds that that material is known at high dose levels to 11 cause some cancer. But, to conclude that the two are connected, 12 you have to have some evidence that the amounts to which the 13 people are exposed might reasonably be thought to produce the 14 effect that is observed, otherwise you may be blinding yourself IB to some other causes and 1 can only conclude that the effect is 16 due to the postulated pollutant if one can decide on the basis | 17 I of the totality of the evidence available that the sort of hazard I 18 observed is of the order of magnitude of the sort of hazard that 19 might be anticipated, so that the situation, the problem in each 20 case is a difficult one which needs a lot of evidence. 1 left 21 it open in relation to vinyl chloride and the vinyl chloride 22 producing plants because we have not yet got sufficiently clear 23 evidence of the dose to which people are exposed that have 24 -produced the measured risk we have been able to measure in the 25 industry concerned. X Tennyaon & Company - Court Reporters London. England 01144-12424164 UCC 073053 no 1 Q It is your opinion, however, that vinyl chloride as a 2 carcinogen and as a mutagen is capable of producingrcancers at 3 exposure levels in the parts per billion? r 4 A `No, I would not express it as my opinion. I would 5 express it saying it is my belief we have to consider that as 6 a possibility. 7 (Whereupon there followed a short adjournment) 8 BY MR DELLI BOVI! 9 Q Dr Doll, are you aware of any human carcinogens that 10 Hermon Dendinger or Fred Wallace were exposed to at Chrysler 11 other than vinyl chloride? 12 A I am not sure. Was not one of them exposed to ethylene 13 dioxide? I am not sure. I have not looked into it. 14 Q Have any of the polyvinyl chloride manufacturers that 15 are Defendants in this case presented you with any evidence in 16 dicating Mr Dendinger or Mr Wallace were exposed to any other 17 human carcinogen? .v I i i 18 A 1 should need to refresh my memory, to look at the 19 papers I have had. 20 Q You indicated in your 1975 presentation to the New 21 York Academy of Sciences: "Cancer is a process in which several 22 factors are likely to participate. A particular chemical carcin 23 ogen is only one factor which interacts with a number of others 24 that may depend on the environment or on the functional state 25 of the body, and a simple linear relationship with one factor Tennyson A Company * Court Reporters London, England 01144*12424164 UCC 073054 111 1 'may be seen in all sorts of complex situations." Do you agree 2 with that statement' today? " 3 A Yes and no. I would not put it quite in chat form 4 ^ today. Ad that time 1 wrote that 1 was fairly confident in my 5 own mind that there was a real effect creating a risk of cancer 6 down to vanishingly low levels. In the past twelve or thirteen 7 years I have learnt more about the repair mechanisms of the cell 8 and I would be more open minded now as to whether that actually 9 was the position or not. I would still say that that is a 10 possibility but I will be much more open minded to the possibility 11 that the human body was capable of dealing with very small 12 amounts of carcinogen and thereby repairing the damage done than 13 I was in 1975. 14 Q By the time you made that presentation in 1975, dozens 15 of workers exposed to vinyl chloride had already died of angio 16 sarcoma of the liver? 17 A I do not think that is quite true, is it. I would i 18 have thought it was under 20 by 1975, but we have the register 19 of cases. That will tell us how many there were. How many were 20 there? 21 Q There were 23 by the end of 1974 and I do not think 22 we can tell from the way the data is presented how many there 23 were in 1975. 24 A That is what I said. Not dozens but of the.order of 25 20 is 1 think what I said. Tennyson & Company - Court Reporters London. England 01144-12424164 UCC 073055 112 1 Q At your presentation in 1975 you were critical, were 2 you not, of the polyvinyl chloride industry's lack of monitoring' 3 its work force over years prior to 1975? ~ 4 A Yea, I had been critical of many industries at their 5 failure to maintain on-going studies or cohort studies of their 6 work as 1 had been teaching this for the last thirty years. 7 Whether the industry was in fact; had in fact started one then, 8 I do not know. The Tabershaw and Gaffey study, when that was 9 first commissioned, I cannot remember now, but it was certainly 10 my view at that time that the industry ought to be organising 11 a cohort study of its workers. 12 Q By 1968 or 1969, when Herman Dendinger first came to 13 work at Chrysler, there had already been within the industry 14 9 angiosarcoma deaths? 15 A That certainly was not known at that time. 16 Q But was that not precisely the point you were making, j 17 that if the industry had done these cohort studies and follow i 18 ups of their workers, that they may well have discovered years ; 19 prior to 1974, the carcinogericity in humans of vinyl chloride? 20 A That was a criticism I made of industries throughout 21 the world, not specifically of the vinyl chloride industry. 22 Their behaviour was no different from all industries in all 23 major countries. Some industries do no cohort studies at all. 24 In the Soviet Union they do not do any at all and I have been 25 nagging them for years that they should. t Tennyson & Company Court Reporters London. England 01144-12424164 UCC 0730S6 113 1 Q Let me read a small excerpt from your 1975 presentation 2 and afterwards my question will be if you still subscribe to 3 this statement today. "I should like to re-emphasise a point 4 that has alre'ady been made several times in this conference; 5 that is, the one made by Dr Schweitzer when he said that all 6 responsible Industries - certainly all those that are large 7 enough to employ a doctor - should maintain an on-going perspec 8 tive study of the health of their working force. That does not 9 mean keeping an eye on them while at work only; it means keeping 10 an eye on them when they leave if they have been employed in 11 the industry for (say) five or more years. Professor Schilling 12 and many other people have been urging this for a long time. 13 How we can have a situation in which a new risk is discovered 14 in a major industry and then have to set up a prospective study 15 to find out what is actually happening to process workers is 16 incomprehensible to me.*' | 17 l A Yes, I have beer* teaching that since the middle 1950s. j 18 Q You referred in your direct examinaiton to an article j 19 - - maybe you did not. One you wrote in 1986 called: "Cancer 20 - a preventable disease" and that was a presentation that you 21 made to the Royal Society of Medicine ? 22 A Yes. 23 Q 1 would like to read to you from page 20 of your 24 -presentation in 1986 that dealt with animal studies.* My questior 25 will be the same as it was with the last paper, that is whether Tennyson & Company - Court Reporters london, England 01144-12424164 ucc 073057 1H 1 you subscribe to that statement today. "Animals, however, vary 2 greatly in the way they absorb, metabollise and respond to 3 different chemicals and there are no observational data to 4 justify sucK an assumption. That is not to say that we should 5 ignore the results of laboratory tests in small rows, as there 6 are sufficient grounds for believing that agents that cause 7 cancer in one animal are quite likely to do so in others and it 8 would be criminal to allow anyone to be exposed unnecessarily 9 to a new chemical that was found to be a powerful carcinogen 10 in several animal species just because there was no human 11 evidence." 12 A Yes. 13 Q With respect to the cancer sustained by Fred Wallace, 14 the mucoepidermoid cancer, you indicated that you did not believe 15 that vinyl chloride was the source of that cancer because such 16 cancers had not been produced in animal experiments? ! 17 . A Yes and not in humans, in the human population or j 18 animal experiments . 19 Q Those were two different grounds for your opinion? 20 A Yes. 21 Q And you have reviewed the pathology report for 22 Mr Wallace to know what cancer he died from? 23 A Yes. 24 Q I would like to refer you to Dr Viola's 1971 paper and 25 the summary which reads in part: "The cutaneous tumfours which Tannyaon A Company Court Reporters London. England 01144-12424164 UCC 073058 115 1 "always appeared/the area in which submaxillary and parotid 2 glands are located, have been histologically recognised as 3 epidermoid carcinomas* papillomas* and mucoepidermoid carcinomas " 4 A Yes 5 Q At page 518 of his 1971 article. Dr Viola states, does 6 he not: "A few tumours showed little nests of isolated pale 7 cells of three types; mucin-producing cells (originating from 8 the duct epithelium of sweat glands or salivary glands); squa 9 mous cells; and intermediate cells with minor tendencies to 10 wards differentiation." 11 A Yes. 12 Q Was it your understanding that Mr Wallace died of a 13 poorly differentiated squamous cell, mucoepidermoid carcinoma----- 14 A Yes, that is of a different organ to the ones that 15 Viola is describing. Viola's description has been discounted 16 since 1974, when it was appreciated that the tumours that Viola j 17 was describing were not tumours that had anything to do with the j 18 salivary glands at all but they were related to a zimbal gland 19 of rats which is a serpaceous gland and has no relationship what 20 soever to a salivary gland. This is uniformally accepted by 21 every cancer research worker to whom I have spoken. At the time 22 Dr Viola made his first observations he was not very experienced 23 with the rat pathology and he attributed them incorrectly. His 24 error has been corrected ever since 1974 and it is not questioned 25 now. > 1 Tannyton & Company - Court Reporters London, England 01144-12424164 UCC 073059 116 1 Q Have you reviewed other scientific articles or case 2 studies associating buccal cavity or cancers of the r*pharynx with 3 exposure to vinyl chloride? r 4 A I 'have read one article relating a cancer of the bucca: 5 cavity to someone who chewed plastic. That is the only article 6 which I could think of which might be relevant to your question. 7 Q Did Tabershaw and Gaffey report an excess of buccal 8 cavity and cancers of the pharynx in 1974 MCA study? 9 A That is quite possible but I would not pay any 10 attention to that because 1 looked at their longer follow-up 11 when they had the more complete data, that is preliminary data 12 and their final data do not show any excess tumours in that cate* 13 gory. There may be one excess compared to the expected, I can 14 not remember. 15 as compared to 13.5. 15 Q Have you referred or been furnished for your review 16 prior to today, with any portions of the hearings held by the 17 Occupational Health and Safety Administration in the United 18 States relating to regulating vinyl chloride following public 1 i 19 announcement of the Goodrich cancer deaths in 1974? 20 A Frankly, I find them too tedious to read and I never 21 read those hearings, 1 prefer to read the basic science on which 22 they are supposed to be based. 23 Q Do you know Mr Thomas Mancuso of the Pittsburgh School 24 of Public Health? 25 A Yes, I do. I Tennyson & Company - Court Reporters London, England 01144-12424164 ucc 073060 117 1 Q Are you very familiar with work in areas of beryllium? 2 A Yes and several other areas. f 3 Q Do you regard him as an expert in the area- in which 4 he practises? 5 A No, I regard him as a very unreliable person. . 6 Q I would like to refer you to a portion of Dr Mancuso's 7 testimony before the Occupational Health and Safety Administration 8 and I would like to know after I read that extract whether or 9 not you agree with it. "Further, the skin tumours frequently 10 develop near the ear and submaxillary or the same areas as the 11 salivary glands. It was postulated by the original investigator! 12 that vinyl chloride may enter the salivary gland system." Do 13 you have opinion on whether vinyl chloride or its active meta- 14 bollites, enter the salivary system in humans? 15 A I should be surprised if they do. I do not see why 16 they should go up against the saliver, but 1 do not know of any 17 results analysing the saliver in the salivary glands so I have 18 not any positive evidence but it seems an unlikely thing. 19 Q "If this/ibsequently confirmed, it raises the questior 20 whether tumours of the parotid glands can also occur as has been 21 demonstrated in the rubber industry and this has been confirmed 22 now by the testimony this morning that cancer of the parotid 23 gland has been observed in animals." 24 A Well, he is incorrect in talking about it fcging observed 25 in animals. v He is basing himself on the erroneous reports of Tennyson 8t Company * Court Reporters London. England 01144-12424164 UCC 073061 118 1 Viola and I am not aware of any excess of cancer of the parotid 2 glands in the rubber industry. Certainly none of the very 3 detailed studies that have been carried out in thisrcountry in 4 the rubber industry have shown any such effect. 5 Q How rare a cancer is a parotid gland carcinoma? 6 A I cannot give you a figure but it is a rare cancer. 7 Q There was a statistically significant increase in the 8 deaths for parotid gland cancers at the Chrysler plant in Ohio, 9 was there not. Dr Doll? 10 MR BUNDAs Objection. 11 BY THE WITNESS: 12 A Not to my knowledge. Was there? I have seen no 13 evidence of that. 14 BY MR DELLI BOVI: 15 Q How is a parotid gland cancer classified under the 16 ICDA8? 17 A It is classified with the cancers of the buccal cavity' 18 and pharynx. i 19 Q Do you know whether a parotid gland carcinoma has its 20 own number? 21 A It has a sub-number, a fourth digit number. I think 22 it is separate from the submaxillary gland. It is a fourth digit 23 number I believe. 24 Q Are you aware of any attempts by Tabershaw- and Gaffey 25 or by any of the other scientific investigators, to break out Tennyson & Company - Court Reporters London, England 01144-12424164 UCC 073062 119 1 from the category of buccal cavity and cancers of the pharynx, 2 parotid gland cancers, so as to report those results* separately? 3 A No. p 4 Q You do not know then whether or not there may, within 5 that group of buccal cavity and cancers of the pharynx, be an 6 excess of parotid gland carcinomas based on the form on which 7 the data has been presented to date? 8 A No. One can be sure it is not a big excess but you 9 cannot be sure that within that group there was not three or foui 10 cases. 11 Q And that brings me to the United States study that you 12 reviewed versus the United Kingdom study. In the United States 13 study, the organisation hired by the MCA only broke down the 14 number of cancers into about 33 categories? 15 A I do not know about only, it seems to me a very large 16 number. It was a very good effort to break them down to as many V I 17 as that. i 18 Q Did not the United Kingdom study use 68 separate cancer 19 categories for reporting purposes? 20 A No, they had 68 different causes of death but nothing 21 like so many cancers. I think there were probably less cancers 22 than in the American study but of the same order. 23 Q Did the United States study report an increase in the 24 total number of cancers among the polyvinyl chloride: workers 25 study? t Tennyson ft Company Court Reporters London, England 01144-12424164 UCC 073063 120 1 A Total number of cancers you said? 2 Q Yes, sir. ? 3 A The answer is no - - sorry, the answer is ryes in 4 comparison With the United States. 383 against 343. 383 against 5 341-73. I must correct that, I am sorry. That is not what they 6 reported. That is the adjustment that I made. They reported 7 less than that. 1 increased the amount to take account of the 8 deaths of unknown cause. I forget now precisely how many they 9 reported. It could only have been about 360, 1 should think. 10 What 1 did was to say, well they were not able to find out the 11 cause of death of about 7% of the men that died and whereas they 12 of course, included them in the total deaths when comparing the 13 total 1500 deaths against the expected 1700, they did not in 14 clude them in the individual causes and whether it is justifiable 15 or not to assume that the deaths for which they did not discover 16 a cause were evenly distributed, were equally distributed among 17 all causes in the same wayvas the deaths for which they did 18 discover a cause, is, of course, anybody's guess. What I did 19 was assume they were and add those deaths on so as to get a 20 worst possible place and that is the figure that I published, 21 but it is not the figure that they reported. That may not be 22 clear. I would be very glad to elaborate on that if that is 23 a confusing point. 24 Q No, I understand what you are saying. Dr Doll. In 25 terms of other cancers, did the United States study indicate a Tennyson & Company Court Reporters London, England 01144-12424164 UCC 073064 mi 1 statistically significant increase? 2 A I do not think they did for any other cancers* 1 am 3 Just refreshing my memory. Apart from the liver, of course. 4 Q Would you look at pages 71 --- 5 A Yes, the brain is down here. Significant excess of 6 cancers of the brain. I am not sure about lympho-reticulo 7 sarcoma. That might be significant. 8 Q On page 71 of your paper on other cancers, do you show 9 a statistically significant excess? 10 A Page 71 is not referring to the American study, is it? 11 You are talking about cancer of the lymphatic-- 12 Q No, 1 am referring to the other cancers, right-hand 13 column, page 71 about two-thirds of the way down? 14 A Ah, yes. Fine. This was the summation, not from the 15 American study, this was the summation of the four studies which 16 I regarded as providing the really important evidence, the main j 17 contribution of which cameactually from the United Kingdom i 18 study. The American study did not show a significant excess of 19 this group of other and unspecified cancers. The four studies 20 added together does and as you will see in the report, I thought 21 the most likely explanation of this was the mis-diagnosis of a 22 few cases of angiosarcoma of the liver which would have appeared 23 as secondary liver cancers. 24 Q Your studies showed an increase in the rate.of lung 25 cancer to those who were heavily exposed? * Tennyson & Company * Court Reporters London, England 01144-12424164 UCC 073065 122"| A It depends what you mean by "increased" . Not, I thinl, 1 2 a significantly increased one. The lung cancer mortality as a 3 whole amongs t the vinyl chloride exposed workers was- almost 4 precisely what was expected on national data, though 1 think 5 national data are very hazardous to use in comparison with 6 observed deaths from lung cancer because the mortality rate does 7 vary so from one part of the country to another and I do prefer 8 to use regional rates but when you broke the lung cancers down 9 to groups of people employed for a longer period against shorter 10 period or observed more than twenty years after first employment 11 compared with those observed for shorter periods, sooner after 12 first employment, then you invariably got a higher mortality in 13 the groups that one might regard as the more likely to show an 14 excess, but the differences in total were not such as to lead 15 to a clear evidence of an excess from lung cancer but just to 16 suggest that there might be such an excess. 17 i Q Did the German and Swedish studies, were they consistent i 18 with that? 19 A No. I will have to refresh my memory. The German one 20 was not, if I remember rightly, but I will have to check. Where 21 are we now. No, the German one did not show an excess, that was 22 23} against 24} expected. The Norwegian and the Swedish ones 23 did, from tiny numbers, both added together, was 5 against 4} 24 - - 8 against 4} expected and the Italian did not shoy any, so 25 when you added the four studies together you got an^observed of Tennyson & Company - Coun Reporters London, England 01144-12424164 UCc 073066 123 1 314 - the half comes in because of some of the adjustments the 2 Germans made against an expected of 30.7, so I would' Bay the 3 subsidiary studies really supported the idea there was no excess 4 from lung cancer but 1 do not think you should put too much 5 weight on the subsidiary studies* I regarded them as subsidiary 6 studies because so much of their period of observation were at 7 a time before any occupational cancer could be expected to occur 8 that is to say the first twenty years after observation and the 9 evidence from the studies is really scientifically trivial. The 10 only thing of any importance amongst them is that they did show 11 that angiosarcoma were occurring in all these plants. That is 12 the only thing I put my money on. 13 Q You say angiosarcomas occur in cases with nine years* 14 latency? 15 A Mot angiosarcomas. One. I 16 Q And you have seen angiosarcomas with exposures of less 17 than fifteen years? v 18 A Yes much less than fifteen years. i i ; 19 (Whereupon there followed a short adjournment) 20 BY MR DELL1 BOVI: 21 Q Dr Doll, if a chemical is found as a result of animal 22 studies to be a potential carcinogen, do you have an opinion as 23 to whether the manufacturer of a product that contains that 24 chemical has responsibility to disclose to its customers that 25 that chemical is in its product? I Tennyson & Company - Court Reporters London, Engfend 01144*12424164 UCC 073067 124 1 MR BUNDAj .Objection. 2 BY THE WITNESS: 3 A That is an impossible question to answer.t It depends 4 on circumstances too much. 5 BY MR DELLI BOVI: 6 Q Do you know whether or not any polyvinyl chloride 7 manufacturer in the United States prior to 1974 disclosed to its 8 customers that its product contained vinyl chloride? 9 A I know nothing about what the polyvinyl chloride man 10 ufacturers disclosed to its customers in 1974 or 1988. I am not 11 aware of their activities. 12 Q Dr Doll, are people in the United States continuing 13 to die from cancers that they contract as a result of occupational 14 exposure to vinyl chloride? 15 A Oh, of course. 16 Q In terms of angiosarcoma deaths, how many have we seen I v 17 to date, reported cases? i i i 18 A Worldwide or in the United States? 19 Q Worldwide. 20 A Worldwide, something of the order of 120. 21 Q Do you have an opinion or have you expressed an 22 opinion as to how many more angiosarcoma cases we are likely to 23 see as a result of occupational exposure to vinyl chloride? 24 A Yes. 25 Q What is your opinion, sir? :. v '* Tennyson & Company Court Reporters London, England 01144-12424164 UCC 073068 125 1 A I said chat I thought it might be something of the 2 order - 1 am speaking from memory - 250, but I might be out by 3 50, 4 Q So*your opinion then in terms of angiosarcoma deaths, 5 is that ve have not yet reached the halfway point? 6 MR BUNDA: Objection. I am going to object again to 7 this questioning on the grounds that it exceeded the scope 8 of direct examination and also on the basis of relevancy. 9 THE WITNESS: Where does this put me in relation to 10 answering questions. We do not have a judge to say he 11 objects to the question or not. 12 MR DELLI BOVI: For the purposes of the questions, you 13 answer my question regardless of his objection----- 14 THE WITNESS: And subsequently? 15 MR DELLI BOVI: They decide if the question will stand 16 or not. 17 THE WITNESS: Would you repeat the question? j 18 BY MR DELLI BOVI: 19 Q Certainly. In terms of the number of angiosarcoma 20 deaths that you would anticipate would result from occupational 21 exposure to vinyl chloride, we have not yet reached the halfway 22 point? 23 A I think that is probably true, yes. 24 Q If, in fact, vinyl chloride causes cancers' in humans 25 v other than angiosarcoma of the liver, there may in fact have beer T*nny*on St Company * Court Reporters London, England 01144-12424164 UCC 073069 126 1 many more people who have died and will continue to die as a 2 result of occupational exposure to that chemical. t 3 MRBUNDA: I an going to object again on the sane 4 grounds as before and also because it calls for speculation 5 So that I will not be interrupting the tape constantly, I. 6 am going to have a continuing objection to this line of 7 question. B BY THE WITNESS: 9 A My estimate is there will be no such deaths occur in 10 the future. 11 BY MR DELLI BOVI: 12 Q On what do you base that opinion, doctor? 13 A I base that opinion on a mixture of animal evidence 14 and human evidence of what we have seen to date of people that 15 have been heavily exposed to vinyl chloride. 16 Q The studies that you have referred to in your review, 17 include only employees that worked in the PVC industry for one j 18 year or more? 19 A Yes, I think that is true. I am just wondering, I 20 think some of the studies included people for shorter periods 21 but I tried to exclude them and 1 think I did in the principal 22 studies. 23 Q What is the reason for using a one year minimum exploy- 24 -ment period as opposed to say, three months? r. 25 i A It is a matter of practicality. There is a big turn- Tennyson & Company - Court Reporters London, England 01144*12424164 UCC 073070 1 over in many industries and the turnover occurs in the early 2 period. By the time people have been employed for sc year they 3 ere likely to stay for a good deal longer and if yoi^ have a 4 shorter period, a much shorter period, you are likely to under 5 estimate the effect that you will observe by including a lot of 6 people with very short periods of exposure. It is a matter for 7 arbitrary decision just which people you should include. Some- e times people go so far as to include only people who had five 9 years exposure. 1 have done that in some studies and it was 10 done in one of these vinyl chloride studies. Some people include 11 people that have had only one day's employment. I personally 12 think that is a very unwise thing to do because you have a very 13 big turnover of short term employees who give you very little 14 details about the effects of short term exposure and make the 15 study very, very difficult to do because you are tracing very 16 mobile people. There is a third reason. People who change 17 their jobs very quickly are a very unrepresentative group on the > i 16 population and there are a number of studies recently that have 19 suggested as a group they have more accidents, more cirrhosis 20 of the liver, various diseases because of their personal charac* 21 teristics. My general rule is to take a year as a practical 22 working rule. That avoids the big turnover of very short term 23 employees but does not reduce the size of the population too 24 -much, but it is an arbitrary decision and I would go with other 25 people using other cut off periods. X Tennyson & Company - Coun Reporters London, England 01144*12424164 ucc 073071 128 1 Q Does the use of a substantial shorter cut off period 2 in a minimum period, say, three months, for example/ have the 3 effect of diluting the potential effects from exposure to the 4 chemical in question? 5 A That is my belief although not all epidemiologists, 6 would take that view. 7 Q And you are aware that in this case. Dr Shindell's 8 study of the Chrysler employees used a three months minimum 9 employment duration rather than one year or more? 10 A Yes. 11 Q It is your opinion then that that would have the effec : 12 of diluting the effects from exposure? 13 A I would think it would. 14 Q Let us take a look also at the cut off period for the 15 study. It is your opinion, of course, that occupational cancers 16 have a latency period? j 17 A Yes. 1 | 18 Q That is, that they take and may take many years betweei 19 the time of initial exposure before the cancer manifests itself? 20 A Yes. 21 Q Is it, therefore, important when you are doing an 22 epidemiologic study, to use a cut off date, a sufficient number 23 of years prior tothe time you do yourresearch inorder for the 24 latent effects ofexposure to the potentialcarcinogen ormutager 25 in issue to manifest themselves? * Tennyson & Company Court Reporters London, England 01144-12424164 UCC 073072 129 1 A You can do it that way, yes. I certainly think there 2 is not much point in including people that started to be employed 3 just in the last year or two. A better thing, of course, to do 4 Is when yon present your results, to present them separately 5 for people that have been observed in the first five years of 6 their employment, five to nine years afterwards, ten to twenty 7 years afterwards et cetera. That is the best thing to do and, 8 of course, it is because of this that I have put so much more 9 stress on the four principal studies because they are all studie ; 10 in which a very substantial number of observations were made on 11 people more than twenty years after their first exposure and 12 many of the other studies that I did not include, including 13 Dr Chiazze's study where they know nothing about the study of 14 exposure, time since first employment, these will all be affected. 15 They will all be affected by the high proportion with the short 16 time since first exposure. That is really equivalent of saying 17 they are not really relevant evidence. Occupational studies, j 18 unless you have a type of cancer which appears very quickly as, 19 for example cancer of the bladder did following exposure to 20 naptafiijd.amine, the evidence within the first ten years, even 21 within the first fifteen years, the first employment does not 22 tell you much about cancer hazards. 23 Q Would you agree that the incorporation into an epidetni424 logic study of recently employed members of a cohort- also has 25 the effect of diluting the effects of exposure to tlfce chemical Tennyson & Company Court Reporters London, England 01144-12424164 UCC 073073 130 1 in question? 2 A Yes, it certsinly does though, of course,a lot of 3 people vill include them because they will have In mind continu- 4 ing the study for longer and you already have them Included. 5 If you begin by excluding them, then in ten years' time when you 6 want to do a follow-up, you suddenly find you have not got some 7 of the people you would like to have in, so most people, when 8 doing an epidemiologic study, do include people who have been 9 employed relatively recently so that they have the material 10 prepared for a continuation study. 11 Q But in terms of the reporting of the analysis that 12 recently employed portion of the cohort would be separately 13 analysed? 14 A That is right. 15 Q Again, if we look at Dr Shindell's study, have you 16 learnt that he included in his study, individuals first employed| 17 potentially as little as $0 days before the cut off period? ! 18 A I cannot remember honestly whether he did that. 19 Q If he had done that, would that also have the effect 20 of diluting the effects of exposure to the chemical in question? 21 A Yes, but of course, it does not imply that he would 22 necessarily have observed a greater risk if he had cut them off 23 because I do not think from memory that he described exactly 24 the date of first employment of all the people, but `if he did, 25 then that is a bald point. * Tennyson & Company Court Reporters London, England 01144-12424164 UCC 073074 1311 1 Q Have you ever attempted to analyse the fourteen cancer 2 deaths in the job categories in which Messrs Dendinger and 3 Wallace were -employedt to determine the latency period? 4 A My understanding is that none of them are likely to 5 have had a long enough latent period to be of any interest, but a I must check, 1 am not sure of the details of this study. 7 Q Incidentally Or Doll, that binder of material you are 8 going through, could you tell me where that came from? 9 A Yes, this was provided for me by the attorneys for the 10 defence. 11 Q What does that binder consist of? 12 A It consists of 26 different sets of papers including 13 most of the ones which you have discussed with me today. 14 Q Could I see it please? 15 A Yes. (Document handed to counsel) 16 Q Did you review all of the materials contained in this 17 binder? 18 A v Il If by that do you mean have I read them before today, 19 yes. 20 Q And are the opinions that you have expressed today 21 based in part on your reliance on the materials contained in 22 this binder? 23 A No. My opinions that I have expressed today are based 24 essentially on the review which I carried out and has.been 25 published in Aprilf but of course, to that 1 have had to add Tennyson & Company - Court Reporters London, England 01144-12424164 XJCC O'750"75 132 1 the details about Mr Wallace and Mr Dendinger which I knew 2 nothing about. I have refreshed my memory about the early papers 3 of Dr Viola and there are one or two new ones like the one of 4 Dr Shindel'l you have talked about and there are some reports of 5 the industrial hygiene reports of the amount of vinyl chloride 6 detected, I think, by NIOSH inspectors in the Chrysler plant, 7 but I need to refresh my memory as to who exactly made those 8 measurements. I think those are the principal new bits of 9 evidence that they drew to my attention. 10 Q One of the documents in that binder is the Molina 11 Swedish study from 1981? 12 A Yes. 13 Q Does that study report: "An elevated risk of morbidity 14 and mortality from tunours in the digestive organs"? 15 A Yes, if you remember, we discussed that before and 1 16 included in my review and decided it was a paper that was too j 17 unreliable to mean anything. The digestive organs that it refers 18 to there, I think, I forget the exact number, but it does not 19 separate out - - no, I cannot comment on that without refreshing 20 my memory, but my view is that that paper is not really, cannot 21 really be regarded as evidence. There are too many weaknesses 22 in the paper. 23 Q Rendering your opinions with regard to the aetiology 24 of the cancers of Fred Wallace and Herman Dendinger,* or your 25 > opinions relating to the potential implication of vinyl chloride. Tennyson & Company * Court Reporters London, England 01144-12424164 UCC 073076 13 y 1 did you rely at all upon the indexes or summaries of their 2 depositions that were provided to you and that you i*ead? 3 A No, no. I would not feel able to do that Without 4 seeing the -entire thing. 5 Q You are aware of the 1984 article by Maltoni that is 6 not cited In your review, reporting angiosarcoma cases among ' 7 workers in the FVC fabrication industry? 8 A No. I had not come across that until I was sent that 9 report. That was news to me. 10 Q Did you receive this document after you authored your 11 report that appeared in the Scandinavian journal? 12 A Yes. I would not have included it anyway - - yes, I 13 would have included the statement that there were angiosarcomas 14 reported in that plant, but I was not covering fabricaters and 15 so the probability is that I would not have included anyway, 16 but I had not seen it. When was it published? 17 Q 1984. Did you personally review or conduct the 18 ' literature review for the report that you authored or did you i i 19 have a research assistant perform that task for you? 20 A No, I did it myself which is to say, of course, one 21 also made use of the automated techniques which medical libraries 22 provide for you. 23 Q In forming the opinions you expressed regarding the 24 cancer sustained by Fred Wallace and Herman Dendinger, did you 25 rely at all on the industrial commission reports that are Tannyson & Company - Court Reporters London, England 01144-12424164 UCC 073077 134 1 contained in the binder that Mr Bunda presented to you? 2 A No, I based my opinion entirely on the fadt that those 3 two types of cancers are not seen in people heavily^exposed to 4 vinyl chloride and not produced by vinyl chloride in animal 5 experiments. 6 Q In connection with your assumptions concerning the 7 vinyl chloride levels in the workplace at Chrysler, did you 8 rely at all on the letters of August 25, 1986 and April 7, 1987 9 by Jack Peterson? 10 A That is the only information I have had, I think thos ; 11 are the only ones in that book, are they not? I have had no 12 other information other than what is provided in that book about 13 the levels at Chrysler works. 14 Q Is it important for an epidemiologist who is investi 15 gating a particular chemical, not to establish preconceived 16 notions or assumptions as to what cancers that chemical can and 17 cannot produce? ,v ; 18 A Yes. 19 Q Have you read at all prior to today, the sworn testi 20 mony of Dr Shindell? 21 A No. 22 Q Have you been furnished prior to today with his testi 23 mony? 24 A No. 25 Q Have you read prior to today, the sworn testimony of Tennyson & Company * Court Reporters London, England 01144-12424164 UCC 073078 135 | 1 any witness in this case? 2 A No. f 3 Q Have you read prior to today the sworn testimony of 4 Herman Dendinger and Fred Wallace? 5 A No. 6 Q In the Environmental Health Associates Study of 1986 7 - and I would like you to refer to your report if you would, at 6 page 62, the right-hand column - it indicates that he studied 9 a total of 10,173 men? 10 A I am sure that is right but I cannot see where you are 11 pointing--- 12 Q The first paragraph of the United States study. 13 A Page 62, I am sorry I was looking at 63. Yes. 14 Q That was his cohort? 15 A Yes. 16 Q Included in that 10,173 men were 1,176 men in five j 17 plants that produced homopolymers and copolymers with or without \ 18 vinyl chloride monomer or polyvinyl chloride? 19 A Yes. 20 Q Is that correct? 21 A Yes. 22 Q So at least potentially incorporated into his data of 23 a cohort of 10,173 men, were 1,176 men that may not even have 24 been exposed to the chemical? * 25 A I think that is unlikely the way it is phrased: Tennyson & Company - Court Reporters London, England 01144-12424164 UCC 073079 136 1 "with or without"* but I am afraid you would have to ask a more 2 experienced chemist than myself as to the implication of the 3 honopolymers and copolymers. f 4 Q If*we look at page 1 of your review* did all four of 5 the principal studies you relied on, the United States, the 6 United Kingdom, the Canadian and the Italian study show an 7 increase above the number expected of the number of observed 8 cancers In the polyvinyl chloride workers? 9 A In comparison with the national expected,,yesThe 10 Canadian was not the national expected, it was the Quebec 11 mortality rates. 12 Q But each of the studies showed an increase in the tota' 13 numbers of cancers? 14 A Yes. 15 Q Dr Doll, do you know why, in terms of the United State!; 16 figures, in Table I there is no data presented at all with respect 17 to liver cancers? ! 18 .i A Yes. The authors were working with a particular 1CD 19 category in which liver and gall bladder were put together as 20 one in the ICD category but they did, of course, publish 21 separately a listing of the 39 cases, using the 7th revision, 22 that they were using, they had not got the separate numbers, 23 they had not got the separation of liver and gall bladder and 24 that is a weakness of their study, but I think we can.assume that 25 the deaths were practically all cancers of the liver. The expected Tennyson & Company - Court Reporters London, England 01144-12424164 UCC 073080 137 1 deaths for cancer of the liver, I think I am right in saying, 2 were not available separately from the American data at that 3 period, but that may be vrong. r 4 Q If we look at Table 4, did the results of the four 5 principal studies. United States, United Kingdom, Canada and 6 Italy, show an increase above that expected for cancers of the 7 mouth and pharynx in the polyvinyl chloride and vinyl chloride 8 workers? 9 A They showed 18 deaths against 16.6 expected. 10 Q For a PMR of 109? 11 A Yes. 12 Q If we go down to Table 5 which reports the studies fron 13 Germany, Norway, Sweden and Italy, encompassing 14 plants, did 14 those four studies combined reveal an increase above the number 15 expected of digestive system cancers excluding cancer of the 16 liver? 17 MR BUN0A: Objection. I am going to object to the form 18 of the question on the basis that when we are talking about 19 an increase you have to have a data point from which you 20 show an increase. I think it is a mischaracterisation of 21 what the table shows. The table shows there is a greater 22 number but 1 do not know if that is an increase or decrease. 23 BY THE WITNESS: 24 A The table showed a greater number but the ^excess was 25 smaller than the deficiency in Table 4 in the principal studies Tennyson & Company Court Reporters London, England 01144-12424164 UCC 073081 ------------------------------------- - 538 1 to which you have not drawn my attention which, of course, was 2 125 deaths against 166.4 expected. When you combing the two, 3 you get an observed which is less than that expected. 4 BY MR DELL! SOVI! 5 Q One of the problems/itiese studies, when they are 6 combined, is that the researchers have not reported their results 7 in a uniform consistent manner? 8 A That is one of the difficulties that one has in 9 combining them and one of the reasons why several o^ the'sub* 10 sidiary studies were regarded as subsidiary. The Swedish study, 11 for example and the Norwegian study, both report their data in 12 such an incomplete way they could not be usefully used, whereas 13 the three of the principal ones reported them in a very detailed 14 way. The Canadian one was not as detailed as one would like. 15 Q The Canadian one only dealt with a total of twenty 16 deaths? 17 A Yes. 1 18 Q And the Canadian one was even less than the total 19 number of cancer deaths at Chrysler? 20 A Yes. 21 Q The Italian study only dealt with 30 deaths? 22 A Yes, but they are both good and important studies in 23 the sense that they had observations on people more than 25 years 24 after they were first employed and they both had cases of angio 25 sarcoma of the liver in them so they were relevant ti> include Tennyson & Company Court Reporters London, England 01144-12424164 UCC 073082 139 1 and it would have been improper to have excluded them. Although 2 the numbers are small, they are of real value in tht they 3 report relevant data. r 4 Q -lit terms of the angiosarcoma deaths in the United 5 States, you indicated In your 1985 article in British Journal 6 for Industrial Medicine that 23 of the 33 cases that had been 7 reported to date in the United States Involved just two factories. 8 Could I refer you to that document. (Document handed to the 9 witness) 10 A Yes. 11 Q Have any of the PVC manufacturers disclosed to you at 12 which of their facilities these large increases in the angio 13 sarcoma deaths were experienced? 14 A I am afraid I cannot answer that question. I cannot 15 remember whether it is in the angiosarcoma register or not. It 16 has not been a question I have been asked. 17 Q Let me combine that point, that is the concentration 1 V , 18 of angiosarcoma deaths at a relatively small number of plants, i 19 with the differences in the results of the data you have reviewe 20 Some show an increase in brain cancer, 6ome show an increase in 21 thyroid cancer, some show an increase in melanomas, some show 22 an excess in the digestive system, some show an excess in lung, 23 some do not. Could those differences and the seeming irrecon 24 cilability of all the data, be due to what you descr-ibed in one 25 of the articles we talked about earlier as the need ?to consider Tennyson & Company - Court Reporters London. England 01144-12424164 UCC 073083 140 1 each facility and the cohorts exposure and the peculiarities of 2 those facilities or the peculiarities of the particular vinyl 3 chloride or polyvinyl chloride resin produced or used by those 4 facilities' into account? 5 A No, that is not the natural interpretation. The 6 natural interpretation is this is exactly what you would expect 7 to find if- you look at 25 different reports and look at 25 8 different cancers in each of them. I guarantee whatever the 9 chemical was, if you looked at as many different cohorts as have 10 been looked at in relation to vinyl chloride and looked at as 11 many different cancers in them, you would find precisely this: 12 It is inevitable. This is exactly what chance means. If you 13 look at 25 different types of cancer, one will show a signifi 14 cant excess by chance. That is the definition. If you look at 15 20 plants and 20 factories, then you are going to get 20 times 16 that number of excesses and they will all be different. If you 17 want to find an excess which you are going to relate to the j 18 particular conditions of the plant, you want to show that it is 19 consistent in other plants that have the same chemical exposure, 20 you want to show it occurs at the right time after exposures 21 and it is concentrated on people who have had longer rather than 22 shorter terms of exposure. All these are things you take into 23 account. What you hsve described is what I would expect to find 24 in any series of studies no matter what chemical you were looking 25 at, irrespective if it was not a carcinogen. * Tennyson & Company - Court Reporters London, England 01144-12424164 UCC 073084 ---------- -------------------------------------------------------------------------------------------------------------m- 1 MR DELLI BOVI: Could we go off the record for just 2 a minute? 3 (O9 ff the record) 4 BY MR DELLI 'BOVI: 5 Q Finally, Dr Doll, there are a number of exhibits that 6 I would like you to identify for me. I understand that a number 7 of those are your only copy and I will be more than happy to 8 substitute a copy of that document for the original but I would 9 like to get the documents marked so we are clear what we do and 10 do not need copies of. n A May I just ask. Will you pay for the photocopying of 12 them or who shall 1 charge? 13 Q Absolutely, I shall be more than happy to, as well as 14 the time of who does it for me. Would you first identify 15 Exhibit Doll 9.(Document handed to the witness) 16 A Yes. 17 Q What is that? v 18 A A version of the United Kingdom report which has been 19 published in the Scandinavian journal. Work, Environment and 20 Health in June this year, provided me by Dr Jones in January, 21 1987. I see that it says the version I received in 16th January 22 It is not the press version and I cannot guarantee that it is 23 precisely the same as that on which 1 based my final conclusions 24 but it is certainly near enough it. t. 25 Q Did you indicate in your review who commissioned Tannyson & Company - Court Raportars London, England 01144*12424164 UCC 073085 142 1 Dr Jones to conduct that study? 2 A Yes, this was carried out by the Government, I suppose 3 the equivalent of NIOSH. Our health and safety executive. 4 Q Would you identify Plaintiffs' Exhibit Doll 10, please? 5 (Document handed to the witness) 6 A Yes, this is a translation of an Italian article that 7 1 arranged to have. The Italian article was sent to me by ICI 8 in this country, it had not been published at the time, it has 9 subsequently been published in English, but I have not got a 10 copy of the English translation, only of the one I had made 11 personally. 12 Q ICI is aEuropean --13 A ICI is a big chemical industry that makes polyvinyl 14 chloride. 15 Q Do you know Dr David Duffield? 16 A No. 17 Q Plaintiffs' Exhibit Doll 11 contains a number of your | 18 publications that I have requested, does it not? (Document 19 handed to the witness) 20 A Yes. 21 Q Your preference is that we not mark the originals of 22 those publications but you will provide me at my expense with 23 copies of the publications thatare listed on that exhibit? 24 A Yes indeed, they are my only copies of my own work and 25 I prefer not to have them marked, but I am very happy to let you Tennyson & Company Court Reporters London, England 01144-12424164 UCC 073086 143 1 have copies. Do you wane copies of the two books? 2 Q I have reviewed them earlier. I do not have a need 3 for copies of either of those. r 4 A -If you could be so good as to initial or that is not 5 necessary. I am sure you will accept my withdrawal of the 6 appropriate two? 7 MR DELLI BOVI: Certainly. 8 MR BUNDA; Rather than sending them directly to 9 Mr Delli Bovi, since we are attaching the list, let us 10 attach the articles to the transcript. So, why don't you 11 provide them to the Court Reporter and she can attach them 12 to the transcript. 13 THE WITNESS: Whatever you suggest. 14 BY MR DELLI BOVI: 15 Q Finally, Plaintiffs' Exhibit Doll 12 is a binder of 16 materials that were presented to you for your review and which 17 you have in fact reviewed Concerning this case? 18 A Yes. 19 MR DELLI BOVI: That is all I have. Dr Doll. Thank 20 you. 21 RE DIRECT 22 BY MR BUNDA: 23 Q I have a couple of questions. I realise the hour is 24 late and we are all tired doing this but 1 just want; to go over 25 one or two things. > I would like to refer you if I could to the Tennyson & Company Court Reporters London. England 01144-12424164 UCC 073087 m 1 1981 study done by Dr Chiazze. Do you have that before you, 2 that is Exhibit 2. ; 3 A Well, we have it in here so I can look atrit here. 4 Q Let's make sure we have the exhibit. Do you have that? 5 MR DELLI BOVIs Certainly I have a pile of materials 6 here. 7 THE WITNESS: I have it here, Exhibit 2. 8 MR DELLI BOVI: Do you mind, we have three copies of 9 this study, could I have one of them please? (Document 10 handed to counsel) Thank you. 11 BY MR BUNDA: 12 Q Did Dr Chiazze when he was doing this study, attempt 13 to determine whether or not those people that he studied in the 14 cohort deaths that he looked at, whether or not all of those 15 people had had exposure to vinyl chloride? 16 A No. In fact, it is quite clear that a lot of them 17 had not. 18 Q How can you tell that? For example, look at Table I ! 1 '! 19 5, please. 20 A Yes, that is the table I had in mind where 61X of the 21 women with breast cancer had no exposure and 72.41 of the 22 controls also selected from women who had died of other diseases 23 had had no exposure and another substantial proportion who had 24 had improbable exposure. 25 Q Of the cohort or deaths that you looked at in your ctucfc Tennyson & Company - Court Reporters London, England 01144-12424164 UCC 073088 145 1 did those people all have exposure to polyvinyl chloride or 2 vinyl chloride? * 3 A Well, there is a possibility that a few did not that * 4 worked in these plants producing homppolyraers and copolymers. 5 I am not quite sure whether they have exposure. Some of. them 6 may not have, but the great majority of all the others certainly 7 did have. would have to check my memory on the United Kingdom 8 study as to whether there were any that had no exposure. I am 9 not quite sure. 10 Q So would it be improper to compare the Chiazze study 11 with your study in terms of comparing the number of deaths? 12 A Oh completely improper. They bear no relation to one 13 another as far as hazards of vinyl chloride are concerned. 14 Q Getting back to the Chiazze study for just a second, 15 why were those particular people in Table 5 looked at to deter 16 mine their exposure? 17 A If I may elaborate, my previous answer --- 18 Q Oh, I am sorry. 19 A I was checking on the United Kingdom study and all 20 5,500 men who were employed had potential exposure to VCM for 21 25X of the work week. I thought that was the position but I 22 wanted to check. Sorry, what was the first question? 23 Q Getting back to the Chiazze article of those people 24 in Table 5 that we looked at before, what was the reason why 25 the exposure information was determined for them? * * Tennyson & Company - Court Reporters London, England 01144-12424164 UCC 073089 146 l 1 A Because there was an excess, a higher proportion of 2 deaths were attributed to breast cancer among the female workers 3 than would be expected if the distribution had beenrthe same 4 as deaths 'in the United States as a whole and he wanted to in 5 vestigate this further and he did the proper thing for an epidem 6 iologist to do in this situation which is to do a nested case 7 control study, that is to say one in which you make special 8 inquiries about the affected patients and then you choose a group 9 of other people who did not develop the same disease but who 10 were matched in certain respects, same age and similar charac 11 teristics like that and compare the exposures of these two group;. 12 That is what Dr Chiazze did. 13 Q What happened when he did that? 14 A Well, he found that of those with possible or definite 15 exposure there were 4.5% of women who died of breast cancer and 16 a possible or definite exposure in 7.5% in their matched control^. 17 In other words, a higher proportion had had possible or definite1i 18 exposure in the women that did not develop breast cancer but j 19 both proportions were extremely small. i 20 Q It also showed, did it not, that a large percentage 21 of women who had breast cancer had no exposure? 22 A It did. 75% had no exposure or improbable exposure. 23 Q What effect did that have on the hypothesis that vinyl 24 chloride was somehow related to breast cancer? : 25 A Oh, I think it made it quite clear that it was not Tennyson & Company - Court Reporters London, England 01144-12424164 UCC 073090 TV7 1 related in any way. 2 Q During the cross examination we heard in the discussion 3 of this article about a significant statistic with regard to 4 all cancers*and large intestine cancers. This breast cancer 5 statistic was also deemed important by Dr Chiazze at first, was 6 it not? 7A Yes. 8 Q Is this case control study which he thereafter did, 9 an example of the pitfalls that you can run into if you jump 10 to conclusions about proportionate mortality results? 11 MR DELLI BOVI: Objection, leading. You can go ahead 12 and answer. 13 BY THE WITNESS: 14 A I think it was a perfectly natural thing to do if you 15 were wanting to see whether the findings that you had found from 16 a proportionate mortality ratio study did have any significance i 17 in relation to the exposure to which the individuals were con- i | 18 cerned. In this case it said certainly as far as the breast 19 cancer was concerned, exposure of vinyl chloride was irrelevant. 20 Q Similarly we have no information available concerning 21 whether those people who were shown as having colon cancer in 22 the study, had any exposure to vinyl chloride? 23 A No such information. 24 Q Dr Doll, you were also asked how payment was made by 25 the CMA to you after you were asked to do this comparison study Tennyson & Company * Court Reporters London, England 01144*12424164 Vcc T5 1 which was recently published and you indicated a donation was 2 made to charity. Do you recall that? 3 A Yes. * r 4 Q Can you please explain to the jury what Is the relation 5 ship or how payment is being made to you as far as your consul 6 tation for the Defendants in this case? 7 A In the same way. I have always refused to take money 8 from Industry for any purpose in order to retain my Independence 9 and 1 made it a condition of appearing as a witness 'in this case 10 that the normal consultation fee should be paid to charity and 11 not to me directly. 12 MR BUNDA: Thank you, sir. That is all the questions 13 I have. 14 FURTHER CROSS EXAMINATION 15 BY MR DELLI BOVI: 16 Q I would like you to assume that the trade industry 17 for polyvinyl chloride manufacturers in the United States, 18 Chemical Manufacturers Association, the Manufacturing Chemists 19 Association sponsored and paid for Chiazze's initial work. As 20 a result of that, would the raw data from Chiazze's original 21 work be in the possession of that industry? 22 MR BUNDA: Objection, there is no foundation laid 23 whether he has such knowledge. 24 BY THE WITNESS: 25 A It depends on the conditions under which Dr Chfazze Tennyson & Company * Court Reporters London, England 01144-12424164 UCC 073092 149 1 undertook the work. If I were to have undertaken the work, 2 although as I pointed out I have never undertaken wprk for pay- 3 ment by industry, the condition would be I would be .-entitled 4 to publish* anything 1 wished about the data, it would be for & me to dispose of. If that was Dr Chiazze's case-, I just do nor 6 know. 7 BY MR DELLI BOVI; 8 Q Are you aware of any efforts by the American polyvinyl 9 chloride manufacturers industry to sponsor a follow-up study 10 of Chiazze's proportional mortality ratio study of PVC fabri 11 cation employees to test his hypotheses regarding the statisti 12 cally significant increases in all cancers, large intestine 13 cancers and other unspecified cancers in both males and females? 14 A 1 think your question includes a few postulates which 15 I would not accept but perhaps it is not necessary for us to 16 go over that. It is a question of the use of "the term "statisti 17 cally significant increases." 18 Q Statistically significant proportional distributions? 19 A Thank you. It is a point of some substance. No, I 20 have no knowledge of what the PVC fabrication industry in the 21 United States is doing at all in regard to anything. 22 MR DELLI BOVI: Thank you. 23 FURTHER RE DIRECT 24 BY MR BUNDA: 25 Q Doctor, I have one more question addressed to the last Tennyson & Company - Court Reporters London, England 01144-12424164 UCC 073093 150 1 question put to you. The continuing updating and following of 2 the workers in the polyvinyl chloride manufacturing;industry, 3 the people who make polyvinyl chloride and the people who make 4 vinyl chloride and the Tabershaw and Gaffey study updated by 5 Cooper and updated again by the MCA, would that or would it not 6 be relevant to the same question regarding issues raised in the 7 Chiazze study? 8 A 1 do not have in mind what issues were being raised 9 by the last question, but it seems to me a comparable question, 10 yes. 11 Q 1 am sorry, what 1 meant by the issues raised were 12 the concerns concerning intestinal cancer, proportional increase> 13 in total cancer and questions concerning breast cancer. Would 14 those be addressed by the study involving polyvinyl chloride 15 manufacturers done by the MCA? 16 A Insofar as there was any suggestion that those cancers 17 were produced by exposure to vinyl chloride, yes. j 18 MR BUNDA: Thank you. j 19 (Whereupon the deposition concluded at 6.40pm) 20 21 22 23 24 25 Tennyson & Company Court Reporters London, England 01144-12424164 UCC 073094 151 1 CERTIFICATE OF COURT REPORTER f 2 3 I, CHRISTINE MARY ARMSTRONG, Accredited Court 4 Reporter, do hereby certify that I took etenotype notes 5 In the foregoing deposition and that the transcript 6 thereof is true and accurate and executed to the best 7 of my skill and ability. 8 9 10 2r Christine M Armstrong 11 Tennyson 6 Company 12 13 14 15 16 17 18 19 20 21 22 23 24 25 VJCC 073095 152 1 CERTIFICATE OF WITNESS 2 3 I hereby declare that the foregoing Is a transcript 4 of my deposition; are the questions asked of me and 5 my answers thereto; that 1 have read same and have made 6 the necessary corrections, additions or changes to my 7 answers that I deem necessary. 8 In witness thereof, I hereby subscribe my name this 9 day of , 198 10 11 12 13 14 15 16 PROFESSOR SIR RICHARD DOLL 17 18 19 20 21 22 23 24 * 25 UCC 073096 1 Correct Ion 2 3 4 B 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 (signed) ERRATA 153 Line No Page Noc t t (date) UCC 073097