Document O19K0mzbLLwb0roQXJymKwNVp

Page 1 1 CAUSE NO. A-167,693 2 JAMES COWEY AND RUTH IN THE DISTRICT COURT COWEY 3 4 PLAINTIFFS, 5 VS. 6 COMPANY, ET AL JEFFERSON COUNTY, TEXAS 7 DEFENDANTS. 58TH JUDICIAL DISTRICT 8 9 10 ORAL AND VIDEOTAPED DEPOSITION OF 11 RICHARD D. IRONS, Ph.D. 12 NOVEMBER 21, 2003 13 14 ORAL AND VIDEOTAPED DEPOSITION OF RICHARD D. IRONS, 15 Ph.D., produced as a witness at the instance of the 16 DEFENDANTS, and duly sworn, was taken in the 17 above-styled and numbered cause on the 21st of November, 18 2003, from 9:40 a.m. to 1:19 p.m., before Kathy Miller, 19 CSR in and for the State of Texas, reported by machine 20 shorthand, at the law offices of Fulbright & Jaworski, 21 1301 McKinney, Suite 4400, Houston, Texas, pursuant to 22 the Texas Rules of Civil Procedure and the provisions 23 stated on the record or attached hereto. 24 25 Page 2 1 2 3 FOR THE PLAINTIFFS: MR. LANCE LUBEL 4 MR. ROBERT BLACK HEARD , R O B I N S , C L O U D , & GREENWOOD 5 910 TRAVIS STREET, SUITE 2020 HOUSTON, TEXAS 77002 APPEARANCES LUBEL 6 7 FOR THE DEFENDANTS UNITED STATES STEEL CORPORATION, ARISTECH CHEMICAL CORPORATION AND USX CORPORATION: 8 MR. STEPHEN C. DILLARD FULBRIGHT & JAWORSKI, LLP 9 1301 MCKINNEY, SUITE 5100 HOUSTON, TEXAS 77010 10 15 11 FOR THE DEFENDANT RADIATOR SPECIALTY COMPANY: MR. JAMES M. RILEY 12 COATS ROSE 1001 FANNIN, SUITE 800 13 HOUSTON, TEXAS 77002-6707 14 ALSO PRESENT: MR. ROY LANGLEY, VIDEOGRAPHER Page 3 1 INDEX 2 PAGE 3 Appearances ...................................... 2 4 5 RICHARD D. IRONS, Ph.D. 6 Examination by Mr. Dillard ....................... 4 7 Examination by Mr. Lubel ........................ 56 8 Examination by Mr. Riley ....................... 121 9 Re-Examination by Mr. Dillard .................. 123 10 Re-Examination by Mr. Lubel .................... 128 11 12 Signature and Changes .......................... 130 13 Reporter's Certificate .......................... 132 14 EXHIBITS 15 NO.DESCRIPTION PAGE 16 1 Curriculum Vitae .................................. 4 2 Black binder containing various 17 articles .................................... 123 3 "Bone Marrow Failure Syndromes," by 18 Neal S. Young .............................. 123 4 "Establishing the Incidence of 19 Myelodysplastic Syndrome" by P.J. Williamson et al ................................. 123 20 5 "2'3'-Dideoxycytidine-Induced Thymic Lymphoma Correlates with Species- 21 Specific Suppression of a Subpopulation of Primitive Hematopoietic Progenitor 22 Cells in Mouse but Not Rat or Human Bone Marrow," by Richard D. Irons, 23 Et al ..........................................123 6 "Clinical-Cytogenetic Associations in 24 306 Patients with Therapy-Related Myelodysplasia and Myeloid Leukemia: 25 The University of Chicago Series" ........... 123 Page 4 1 (Exhibit 1 was marked.) 2 THE VIDEOGRAPHER: This videotaped 3 deposition of Dr. Richard Irons is being taken on 4 November 21, 2003. The time is approximately 9:45 a.m. 5 We're now on the record. 6 MR. DILLARD: Good morning, Dr. Irons. 7 Would you raise your hand and be sworn by our court 8 reporter? 9 RICHARD D. IRONS, Ph.D., 10 having been first duly sworn, testified as follows: 11 EXAMINATION 12 BY MR. DILLARD: 13 Q. Tell us your name, please, sir. 14 A. Richard D. Irons. 15 Q. Where do you live, sir? 16 A. In Boulder, Colorado. 17 Q. And what is your occupation or profession? 18 A. I am a toxicologist and a pathologist. 19 Q. How are -- I was going to ask you how you're 20 employed. Where are you employed? 21 A. I am employed at the University of Colorado 22 Health Science Center in Denver, and at Fudan University 23 in Shanghai, China. 24 Q. And how long have you been employed by the 25 University of Colorado Health Science Center in Denver? 1 A. Since 1989. So, approximately 14, 15 years. 2 Q. You also mentioned another university in 3 Shanghai, China, and I am not sure I can pronounce the 4 name. Would you say it again? 5 A. Fudan. 6 Q. Fudang? 7 A. "Don." 8 Q. Fudan. How long have you been employed by 9 Fudan Medical Center in Shanghai, China? 10 A. I have been a member of the faculty there for 11 approximately three years. 12 Q. You mentioned that you are a toxicologist? 13 A. Yes, sir. 14 Q. What is toxicology? 15 A. Toxicology is the science of poisons, or the 16 adverse effects of drugs and chemicals. 17 Q. You mentioned that you are a pathologist? 18 A. Yes. 19 Q. What is pathology? 20 A. Pathology is the study of the development of 21 diseases and the laboratory diagnosis of diseases. 22 Q. What do you do at the University of Colorado 23 HealthScience Center? 24 A. I am Professor of Toxicology in the School of 25 Pharmacy. I am Professor of Pathology in the School of Page 5 Page 6 1 Medicine. I am Director of the Cancer Causation 2 Prevention Program in the Comprehensive Cancer Center at 3 the University of Colorado. 4 Q. I want to get back to that more in just a 5 moment, but first I'd like to ask you about your 6 educational background. If you would tell the jury 7 first of all where you attended school after -- after 8 high school. 9 A. Raymond College, University of the Pacific. 10 did my undergraduate studies in chemistry, political 11 science, and liberal arts. 12 Q. And then what additional formal education did 13 you receive? 14 A. I took graduate training and a masters in 15 medical technology at University of California San 16 Francisco. I then went to the University of Rochester 17 School of Medicine, and obtained a Ph.D. in toxicology. 18 Following that, I did three years of fellowship in 19 pathology at Strong Memorial Hospital, training in 20 general pathology and clinical pathology. 21 Q. Let's talk about -- and excuse me, what year 22 did you receive your -- your Ph.D. and your doctorate in 23 toxicology? 24 A. 1974, I believe. 25 Q. And then you said you completed three years of 1 additional training -2 A. That's correct. Page 7 3 Q. -- in pathology? 4 A. Yes. 5 Q. Let's talk about your professional experience 6 after you completed your formal education and the 7 additional three years of training. If you would start 8 in 1976 or '77, and just bring us up to the present 9 time, discussing it briefly, please. 10 A. From 1977 until 1988, I was a scientist and 11 senior scientist at the Chemical Industry Institute of 12 Toxicology in Research Triangle Park, and a member of 13 the faculty of Duke University. 14 Q. What did you teach at Duke University? 15 A. Toxicology and some pathology. 16 Q. How long did that tenure last? 17 A. Until I went to the University of Colorado in 18 1988, '89. 19 Q. Where you have been ever since? 20 A. Yes. 21 Q. Are you certified or licensed as a specialist 22 in your field? 23 A. Yes. I am board certified by the American 24 Board of Toxicology. I'm certified as a clinical 25 laboratory scientist in the State of California, and as Page 8 1 a laboratory director in China. 2 Q. How does one become board certified in 3 toxicology? 4 A. You have training. You have to have training 5 that is -- that qualifies you for sitting for the board 6 exams. You apply to take the exam, and if admitted then 7 you take an examination over a two-day period. It's 8 then renewed every five years by exam. 9 Q. How long have you been board certified in the 10 field of toxicology? 11 A. I believe since 1980, although I'm not 12 positive. First -- yes, first examination was in 1980. 13 Q. And then you take a recertification every five 14 years? 15 A. Yes. 16 Q. Tell the Ladies and Gentlemen of the Jury some 17 of the professional organizations and societies of which 18 you are a member. 19 A. I'm a member of the Society of Toxicology. 20 I'm a member of the Association of Investigative 21 Pathology, Association -- American Society of 22 Hematology, the International Society of Experimental 23 Hematology, among others. 24 Q. At least one or two of those organizations 25 contain the name -- or the word "hematology" in it. 1 What is hematology? Page 9 2 A. Hematology is the branch of science and 3 medicine that deals with diseases of the blood and bone 4 marrow. 5 Q. You're not a medical doctor? 6 A. No. 7 Q. Let's talk about your teaching experience. 8 Can you describe for the Ladies and Gentlemen of the 9 Jury, give us an overview of your teaching experience? 10 A. Depending upon the positions that I've held, 11 I've taught numerous subjects. Currently I teach 12 immunology. I lecture in toxicology, and I lecture in 13 hematopathology, which is the branch of pathology that 14 is specifically -- that specifically deals with the 15 diagnosis of diseases of the blood. 16 Q. And bone marrow? 17 A. Bone marrow, yes, that's correct. 18 Q. And what are your primary areas of 19 professional interests and research? 20 A. My principal areas of research are on the 21 pathogenesis, studying the -- the development and cause 22 of diseases of the blood and immune systems, and in the 23 differential diagnosis of those diseases. So, looking 24 at the effects of drugs and chemicals on the development 25 of those diseases as well as in the diagnosis of those 1 diseases. Page 10 2 Q. Let's talk a moment about your professional 3 writing and editorial experience. Can you tell the 4 Ladies and Gentlemen of the Jury some of the 5 professional journals on whose boards you've served, 6 whose editorial boards you've served? 7 A. Quite a few: Certainly the Journal of 8 Toxicological Sciences, Toxicology and Applied 9 Pharmacology, Journal of Experimental Pathology, several 10 others. 11 Q. Have you published articles in -- in one or 12 more of these journals and in other professional 13 scientific journals? 14 A. Yes. 15 Q. Approximately how many articles, books, and 16 book chapters have you published in professional 17 publications, including professional journals? 18 A. I think on the order of 100 -- probably 140 19 peer-reviewed papers and journals, and probably between 20 ten and 20 book chapters or books. 21 Q. You said peer reviewed. What does that mean? 22 A. The basic process that scientists use for 23 publication of original research is to publish in 24 journals that basically review manuscripts that are 25 submitted to them by having them reviewed by independent Page 11 1 scientists; and if they satisfy that review process, a 2 review of peers, then they're published. 3 So, peer review means research and the product 4 of research papers that are reviewed by independent 5 scientists and then accepted for publication. 6 Q. Have you served as a peer reviewer on -- for 7 articles that obviously where you -- where you were not 8 the author? 9 A. Yes, many times. 10 Q. And what is the process there for peer review? 11 A. Well, the process is that if you submit an 12 article for publication at any of the major scientific 13 or medical journals, then those papers are then 14 forwarded to independent scientists who review them for 15 meeting criteria with respect to rigor, appropriate 16 scientific methodology, appropriate interpretation of 17 results and conclusions, and may make some suggestions 18 on how to improve them; and through the journal and the 19 editorial office of the journal, you have an opportunity 20 to respond to those, and the ultimate product is, in 21 fact, a paper that's been accepted for submission 22 through this process of peer review. 23 Q. Have any of the professional articles, books, 24 or book chapters that you have authored dealt with 25 subjects including benzene, benzene toxicology, the bone 1 marrow,bone marrow toxicology, the causation of 2 diseases of the blood, and blood forming organs? 3 A. Yes. 4 Q. Approximately how many? 5 A. Certainly 80, probably between 80 and 90. 6 Q. And over what period of time? 7 A. Basically since 1977, so the last 30, 35 8 years. 9 Q. I am going to show you what's been marked as 10 Exhibit 1, and ask you if that is a correct copy of your 11 current resume? 12 A. Yes. I think so. 13 Q. And does that list these various articles, 14 books,and book chapters that you have authored? 15 A. Yes. 16 Q. As well as your work experience, your 17 educational experience, the training you've received, 18 the teaching experience that you've described for us? 19 A. Yes. 20 Q. Okay. Thank you. 21 Dr. Irons, today is November 21, 2003, and 22 we're here taking your deposition. When this testimony, 23 this videotaped testimony, is presented to the jury in 24 this case in December of this year, where will you be at 25 that time, sir? Page 12 1 A. I will be in Shanghai, China. Page 13 2 Q. For what purpose? 3 A. I am the director of a joint clinical and 4 molecular laboratory in Shanghai that currently has 5 responsibility for diagnosing diseases of the blood and 6 immune system for 23 hospitals in Shanghai; and during 7 the month of December I am on call, so I have to be 8 there. 9 Q. What is your specific involvement with that 10 project? 11 A. The laboratory currently supports a series of 12 studies referred to as the Shanghai Health Project that 13 I am principal investigator for, and that is a project 14 that is involved in characterizing the cause and 15 pathogenesis of all hematopoietic and lymphoid diseases 16 that present in Shanghai hospitals over the course of a 17 five-year period; and also is looking directly at the 18 effects of occupational exposure to benzene in the 19 development of diseases of the blood and bone marrow. 20 Q. What is a hematopoietic or lymphoid disease? 21 What is meant by that? 22 A. Lymphoid diseases are diseases of the immune 23 system and lymphocytes. The major disease entity that 24 we usually are involved in looking at is lymphoma. 25 Q. And what is a hematopoietic disease? Page 14 1 A. Hematopoietic is a disease of the blood, blood 2 forming organs. So hemo means blood, and so 3 hematopoietic really is a technical term for diseases of 4 the blood and blood forming organs. 5 Q. Are you familiar with the category of diseases 6 known as myelodysplastic syndromes? 7 A. Yes, I am. 8 Q. Would those qualify as diseases of the blood 9 or blood forming organs? 10 A. Most certainly. 11 Q. Who are the major participants in the study 12 that's being conducted in China? 13 A. The prin -- the study's being conducted 14 through a collaboration between the University of 15 Colorado Health Sciences Center, Fudan University in 16 Shanghai, the Shanghai branch of the Chinese C.D.C., and 17 the Institute of Public Health Supervision, which is the 18 Shanghai -- a -- the Chinese equivalent of OSHA, 19 Occupational Safety and Health Administration. 20 Q. Many of us may not be familiar with -- with 21 Shanghai, the city where this work is being conducted. 22 Is that a rather large city? 23 A. Shanghai is a city of 17 million people. 24 Q. How would that compare to, say, New York City 25 that some of us would at least be familiar with? Page 15 1 A. New York, if you take the greater -- the 2 greater New York metropolitan area, it's probably a 3 little larger; but New York itself is smaller. So, 4 Shanghai is a very, very large city. 5 Q. How long has this study been underway? 6 A. It's been three years in development. We've 7 been actively supporting diagnosis in Shanghai since 8 July. We have approximately another four years to go on 9 the study itself. The laboratory which is supporting 10 the study and diagnosis is also intended to continue in 11 perpetuity as a clinical laboratory after the study is 12 complete. 13 Q. When you say you have been supporting the 14 diagnosis, what -- what do you mean by that? 15 A. Part of the agreement and collaboration that 16 we're involved in is that during the time of the study, 17 during the period of time where the actual clinical 18 research is being conducted, the laboratory will also be 19 the principal laboratory supporting the diagnosis of 20 blood and lymphoid diseases for the 23 participating 21 hospitals in Shanghai. 22 Q. And are you involved in that process of 23 diagnosing? 24 A. Yes, I'm the director of the laboratory. 25 Q. Who do you report to? Who is overseeing the 1 study? Page 1 6 2 A. The -- the study oversight is performed by two 3 international committees. One is an external scientific 4 review panel that's made up of physicians and scientists 5 from around the world who have specific specialization 6 in areas that are covered under the study; and so from a 7 scientific standpoint I report to them in terms of 8 conduct, procedures and operations. There's also an 9 international ethics panel, review panel, that I'm 10 responsible to in terms of meeting the clinical criteria 11 and clinical ethical standards that are defined both by 12 U.S. and Chinese law. 13 Q. Who is sponsoring this study? 14 A. The study is sponsored through international 15 consortium that is comprised of the five major petroleum 16 companies worldwide. 17 Q. And how is independence from the -- of the 18 study from the sponsors maintained? 19 MR. LUBEL: Objection, form. 20 A. Well, as I said, the actual reporting line of 21 chain of command, if you will, is that I report to these 22 independent panels with respect to the operation of the 23 study. A l l clinical trials, on an international basis 24 in general, but specifically in the United States, 25 whether they're performed by government agencies as Page 17 1 sponsors, or pharmaceutical companies, or anyone else, 2 are governed under a set of laws and rules that are 3 established by the U.S. National Institutes of Health 4 and the Food and Drug Administration through an office 5 that's called the Office of Human Research Protection. 6 So, all clinical trials have to meet standards of 7 independence and regulations that are set forth in those 8 guidelines, and we meet those standards. 9 MR. LUBEL: Objection, nonresponsive. 10 Q. (BY MR. DILLARD) Dr. Irons, have we asked you 11 to address certain subjects in this case of Mr. James 12 Cowey? 13 A. Yes. 14 Q. What specific subject areas have we asked you 15 to address in this case? 16 A. You've asked me to address the toxicology of 17 benzene, and what's known about the effects of benzene 18 on biological systems and the development of disease; 19 specifically, diseases of the blood forming organs. 20 You've asked me to enunciate and to describe the 21 criteria that scientists use in determining causal 22 inference or the cause of disease associated with 23 different etiologies or exposure to individual agents. 24 You've asked me to evaluate the expert report of 25 Dr. Levy submitted in this case, and you've asked me to 1 render an opinion with respect to the likelihood that 2 Mr. Cowey's disease could have been caused or 3 contributed by his exposure to benzene. 4 Q. Okay, sir. I want to go into each of those 5 separately in a moment, but first I want to ask you what 6 in general you have reviewed in connection with your 7 work in this case? 8 A. I reviewed the materials that were given to me 9 associated with this case, the medical records of 10 Mr. Cowey, the depositions of Mr. and Mrs. Cowey, the 11 expert report of Dr. Levy. I've reviewed the scientific 12 and medical literature concerning the criteria for 13 determining causal inference or causation, the 14 literature concerning the development and pathogenesis 15 of the blood diseases that are at issue in this case. 16 And I've reviewed a report by Mr. Spencer. 17 Q. Okay, sir. Going back to the subjects that 18 you mentioned that you were asked to address, let's take 19 the first one. What was that again? 20 A. The toxicology of benzene, what's known about 21 the effects of benzene and the diseases that it causes. 22 Q. And what specifically have you done in that 23 regard, insofar as Mr. Cowey's case? 24 A. I reviewed that literature which I am familiar 25 with, in the context of what we know about the effects Page 18 Page 19 1 of benzene on the blood and blood forming organs, and 2 specifically on the development of acute myelogenous 3 leukemia and myelodysplastic syndrome. 4 Q. Is it your understanding that Mr. Cowey has a 5 form of myelodysplastic syndrome? 6 A. Yes. 7 Q. What -- what form of myelodysplastic syndrome 8 do you understand that he has? 9 A. The specific subtype of MDS that Mr. Cowey has 10 been diagnosed with is called refractory cytopenia with 11 multilineage dysplasia, or RCMD. 12 Q. RCMD? 13 A. Yes. 14 Q. I want to talk more about RCMD in a moment. 15 The second subject area that we had asked you to address 16 again, sir, was what? 17 A. The criteria that scientists use in 18 establishing a causal relationship, or determining that 19 a causal relationship, in fact, exists between a given 20 etiology or cause and a disease. In this particular 21 case, the issues pertaining to specifically the exposure 22 to benzene and the development of hematopoietic 23 diseases. 24 Q. And when you say the -- the scientific 25 criteria that is used, what -- what do you mean by that? Page 20 1 A. There are several different paradigms or 2 patterns that have been described and adopted in the 3 past for use in formalizing criteria that scientists use 4 in determining causation. Science plays by rules and 5 it's necessary to apply a standard set of rules to 6 determining what is an appropriate level of evidence to 7 support a causal relationship between an agent or a 8 potential etiology and a specific disease. Several 9 different criteria have been set forth over the last 10 several decades. All of them basically meet the same 11 standards of criteria that are referred to variously as 12 Bradford Hill criteria, Henle-Koch Postulates, and more 13 recently Evidence Based Medicine. But they all 14 incorporate the same basic standards and criteria. 15 Q. Would you say that their -- these are rules, 16 did you say, that scientists go by? 17 A. Basically, yes. 18 Q. Why -- why is that important, to go by these 19 rules? 20 A. Because in the absence of setting up criteria 21 that can be generally agreed upon in the scientific and 22 medical communities, we have no basis for developing 23 standards to evaluate causation or to look at the 24 effects of exposure to agents on the development of 25 disease. Page 21 1 These criteria apply not only to causation of 2 disease, but also to evaluating treatment and the use of 3 drugs or other therapies in treating disease. So, the 4 same basic criteria are used in both situations to 5 ascertain the effects of exposure to drugs or chemicals 6 or other agents and the development of disease. 7 Q. If someone gets a disease and in their past 8 they may have had an exposure to something that is 9 associated with causing that disease, can you conclude 10 that that exposure necessarily caused that person's 11 disease? 12 A. No. 13 Q. Why not? Why isn't it that simple? 14 A. Well, because, first of all, as a 15 toxicologist, I have to consider the fact that there's 16 no such thing as no exposure. There's no such thing as 17 zero. We've all been exposed to an innumerable number 18 of agents in our lifetime at some level or another. 19 We've all been exposed to agents that have the potential 20 to cause different diseases, and the issue or the 21 question of whether or not a specific agent caused a 22 specific disease requires more than simply knowing that 23 under certain circumstances that agent may be associated 24 with development of disease. 25 Q. Well, how does science go about unraveling it Page 22 1 and getting to the bottom of it in an individual case? 2 A. One has to look at the criteria in the 3 peer-reviewed literature that relates to the 4 quantitative association of exposure to a given agent. 5 Q. What's -- now what's that mean now? 6 A. With respect to the amount of exposure, or the 7 dose that an individual has received, what is that dose? 8 And, with respect to the diseases that have been 9 associated with that agent, what are the specific 10 diseases that have been shown to be significantly 11 increased in terms of incidents, as a result of or 12 associated with specific exposures to that agent? So, 13 quantitative epidemiology, human studies, that 14 characterize the disease processes that are associated 15 with exposure to specific amounts of a given substance. 16 Q. Is this something in the published literature? 17 A. By definition, peer-reviewed quantitative 18 epidemiology. 19 Q. Is published? 20 A. Yes. 21 Q. Now, you referred to these scientific 22 principals earlier, Bradford Hill, and one other, and I 23 don't recall the name of it, but where are these set 24 forth, and how did they become the rules of what the 25 scientists go by in determining whether a particular Page 23 1 exposure may have caused a disease? 2 A. They have been published variously in the 3 published literature. They have been the subject of 4 many conferences and proceedings, and many different 5 bodies and organizations have adopted them in one form 6 or another. They've been described in numerous 7 publications in the past 40 years or so, 40 or 50 years. 8 Q. Did you note in reviewing Dr. Levy's report 9 that he himself refers to these rules? 10 A. Yes. 11 Q. And Dr. Levy, of course, for the benefit of 12 the -- of the jury, is the expert retained by the 13 plaintiff in this case? 14 A. That's my understanding. 15 Q. Focusing on the rules that you scientists go 16 by in determining whether a particular substance may 17 have caused a particular disease, can you -- can you 18 walk us through them? And I may have some questions as 19 we go through them, but can you walk us through them and 20 explain what these rules are that you follow in as 21 simple terms as you can for my benefit? Can you do 22 that? 23 A. Certainly. The first criteria that is an 24 absolute requirement in determining causal relationship 25 is the availability of peer-review quantitative Page 24 1 epidemiologic data, epidemiologic studies in humans that 2 provides strength of evidence, quantitative statistical 3 association between exposure and disease. That's the 4 first one. 5 A second criteria that is related to that is 6 if you have multiple studies that meet those criteria, 7 that there is consistency, or a general consistency, 8 among those studies. So that if you have more than one 9 study, do you see a consistent pattern or a predominant 10 pattern? Because each of these studies, especially 11 studies involving humans, vary with respect to their 12 design, populations they look at, precise exposure 13 conditions. So, under what conditions of exposure, and 14 what occupations, under what particular circumstances do 15 you see this pattern, and is it consistent? 16 The third deals with specificity, and 17 specificity is very important in how -- the conclusions 18 you reach based upon the data we've just discussed. 19 Specificity with respect to exposure. Do the studies 20 look at exposure to the specific agent that is in 21 question, or at issue, or do they look at exposure to a 22 variety of different agents, or can you tell whether or 23 not they are looking at a given exposure? 24 Also, specificity of disease. What are the 25 criteria that were used in measuring outcome in these Page 25 1 epidemiological studies and are they looking at the 2 specific diseases that are in question? Do they look at 3 a variety of different diseases? Are the criteria for 4 diagnosis the same or comparable? And it's not 5 appropriate, for example, to mix or match, to look at 6 exposure to one compound or chemical and assume that it 7 applies to all others; and it's also not appropriate to 8 look at a specific disease and then extrapolate to other 9 diseases that are not the same as the disease you're 10 looking at. So, specificity is a very important 11 criteria. 12 Another criteria that is important is the 13 issue of a temporal relationship, or the time frame that 14 surrounds the development of disease and exposure, and 15 this is important for determining whether the duration 16 of exposure is appropriate based upon our knowledge of 17 the pathogenesis of the disease, and whether or not the 18 exposure, for instance, preceded the development of 19 disease in some cases. So latency and temporal 20 relationships can be an important issue. 21 Another very important issue is the issue of 22 dose response. 23 Q. What is meant by dose response? 24 A. A cardinal tenet of toxicology is that the 25 response to exposure to a given drug or chemical is Page 26 1 going to be proportionate to the dose that the 2 individual received, that if you increase the dose, you 3 increase the response; you decrease the dose you 4 decrease the response. This applies to populations. It 5 also applies to individuals. The dose response is a 6 cardinal tenet of toxicology and medicine, and 7 epidemiologic studies which are really looking at 8 associations in large groups of individuals have a 9 primary requirement to -- to -- to characterize and 10 establish dose response in order to provide credibility 11 with respect to the relationships that they purport to 12 describe. 13 Q. I want to ask you some more about dose 14 response. What -- what does a scientist have to know 15 before you can say that an exposure caused a particular 16 disease? 17 A. Well, as I said, you have to understand what 18 the dose has been to which an individual has been 19 exposed, and whether that dose has been -- that dose has 20 been shown in quantitative studies to be associated with 21 the development of that disease. If the dose that an 22 individual receives is less than a dose range or range 23 of doses that's been shown to be associated with the 24 development of that disease, then you cannot opine that, 25 in fact, that substance caused that specific person's Page 27 1 disease. So, dose response is a very important concept 2 in pharmacology, in drug development, and toxicology. 3 And it has -4 MR. LUBEL: Objection, nonresponsive. 5 Q. (BY MR. DILLARD) Can you give us some 6 everyday examples of dose response, what is meant by 7 dose response, so that we can relate it to -- to our 8 facts? 9 A. As I said before, to a toxicologist there's no 10 such thing as zero. There's also no such thing as 11 nontoxic. Every substance is potentially toxic under 12 the -- under certain conditions and at certain doses. 13 Water can be lethal. Water can be toxic. If you ingest 14 too much water, too rapidly, it can kill you. It's not 15 easy to do, but it can be done. 16 Everything follows a dose response, either 17 both in terms of beneficial effects for drugs, as well 18 as adverse effects which can also be associated with 19 drugs and chemicals. 20 A good example is aspirin, which everyone is 21 familiar with and most people are -- recognize that 22 aspirin can be used to -- as an analgesic, as an agent 23 to reduce pain associated with headache or minor aches 24 and pains. And usually the recommended dose of aspirin, 25 in these -- and under these conditions would be two 1 typical tablets over a four to six-hour period. 2 Many people may not be aware that lower doses 3 of aspirin, a half or a third of that, taken every day 4 or every other day, are actually associated with a 5 decreased risk of cardiovascular disease, because 6 aspirin also has an effect on blood clotting, and it 7 minimizes clotting at lower doses. But there are 8 statistical studies, quantitative epidemiology studies, 9 that show that at lower doses than what are normally 10 used to treat headache, can have a very significant 11 impact on the development of cardiovascular disease. 12 It's protective. 13 Some people who have chronic inflammatory 14 conditions such as arthritis, they may be prescribed 15 larger doses of aspirin than the typical amount we would 16 take for headache. They may be asked to take upwards of 17 maybe five or eight -- equivalent of five or eight 18 aspirins, which would also -- which would have an -19 reduce pain but also reduce inflammation. At the same 20 time that people take those doses of aspirin, they may 21 also experience some side effects such as 22 gastrointestinal upset or irritation. That would be an 23 adverse effect that's related to dose. 24 As they increase taking aspirin, if one were 25 to take say upwards of 12 or 20 aspirin tablets, you Page 28 Page 29 1 might have some of the same beneficial effects that 2 we've just talked about in terms of analgesia, decreased 3 inflammation, but you're going to begin to have very 4 serious gastrointestinal upset. You're likely to have 5 ringing in the ears, or tinnitus. You may begin to have 6 symptoms associated with dizziness or not feeling right, 7 and as you continue to take more aspirin those symptoms 8 will become much more prominent. Between 20 and 50 9 aspirin, you're going to become delirious. You're going 10 to have problems relating to your environment. You may 11 lose consciousness, go into coma. And between 50 and 12 100 aspirin, you may proceed into metabolic and 13 respiratory acidosis. You will go from coma to 14 basically a near death situation and, in fact, you can 15 die from that. It's a very difficult condition to 16 manage from the standpoint of clinical toxicology. 17 So, there's an example of dose response going 18 from low to high that includes the positive effects of a 19 drug, aspirin, as well as the negative or adverse 20 effects. 21 MR. LUBEL: Objection, nonresponsive. 22 Q. (BY MR. DILLARD) If you don't know the dose 23 of a particular exposure, can you say that that exposure 24 caused a particular person's disease? 25 MR. LUBEL: Objection, form. Page 30 1 A. No. 2 Q. (BY MR. DILLARD) Why not? 3 A. As I said before, dose is a very important 4 marker or benchmark with respect to comparing the 5 probability the disease can occur as a function of 6 exposure. If you have no idea what the dose is, you 7 cannot opine that an agent caused the disease. 8 MR. DILLARD: Mr. Lubel has requested a 9 brief recess. 10 MR. LUBEL: Thank you. 11 THE VIDEOGRAPHER: Going off the record. 12 Time is approximately 10:27 a.m. 13 (A break was taken.) 14 THE VIDEOGRAPHER: We're now back on the 15 record. Time is approximately 10:31 a.m. 16 Q. (BY MR. DILLARD) Dr. Irons, the third area 17 that you have told us you had been asked to review in 18 this case had to do with the plaintiffs' expert, 19 Dr. Levy. Have you reviewed his report? 20 A. Yes, I have. 21 Q. And I'd like for you to tell us whether or not 22 Dr. Levy followed proper scientific methods as you've 23 described them in reaching his opinions that are 24 expressed in that report? 25 MR. LUBEL: Objection, form, speculation. 1 Q. (BY MR. DILLARD) Do you have an opinion as to 2 whether or not he followed proper scientific methods in 3 reaching the opinions that he expresses in his report? 4 A. Yes, I do. 5 Q. And what is that opinion? 6 A. That the methodology that he used in reaching 7 his opinions does not conform to the criteria that I 8 have described, that are variously referred to as 9 Bradford Hill criteria, Evidence Based Medicine, or 10 other paradigms that meet comparable standards. 11 Q. Why do you say that? 12 A. He does not rely primarily on peer-reviewed 13 quantitative literature to support his opinions. He 14 includes secondary literature, nonquantitative 15 literature, opinions, editorials, in addition to the 16 quantitative epidemiologic literature. 17 He also does not perform any type of analysis 18 of dose in arriving at a conclusion -- the conclusions 19 he does with respect to the causation of Mr. Cowey's 20 disease. 21 Q. Referring back to these scientific rules that 22 scientists follow, the first one you listed a moment ago 23 was peer-reviewed quantitative epidemiologic data -24 A. Yes. 25 Q. -- which finds a statistical association Page 31 1 between an exposure and a disease? Page 32 2 A. That's correct. 3 Q. What deficiencies does Dr. Levy's opinions -4 what deficiencies do Dr. Levy's opinions have in that 5 specific -- in that particular regard? 6 A. The principal publications that he refers to 7 in reaching his conclusion with respect to Mr. Cowey's 8 disease include papers that did not measure benzene, 9 look specifically at benzene; but instead looked at a 10 variety of different mixed solvent exposures and did not 11 quantitate benzene exposure. 12 At the same time, these same references did 13 not meet criteria specificity with respect to relating 14 exposures to specific disease, in this particular case 15 the general category called myelodysplastic syndrome. 16 In some cases, there's no basis to conclude that 17 myelodysplastic syndrome was in fact the specific 18 disease in question. 19 In one particular case, there was no 20 statistically significant increase in myeodysplastic 21 syndrome seen in the paper. 22 In this particular case, the -- the criticisms 23 that I'm raising don't speak to the general issue of 24 causation, but do speak to the methodology that was used 25 in -- that he used in arriving at his conclusions. Page 33 1 Q. Do you have his report there handy? 2 A. Yes, I do. 3 Q. What is your understanding of the allegation 4 that's being made in this case as far as Mr. Cowey is 5 concerned? 6 A. My understanding is that the allegation is 7 that Mr. Cowey's disease, refractory cytopenia with 8 multilineage dysplasia, a form of myelodysplastic 9 syndrome, was caused as a result of his exposure to 10 benzene over the years, and a product called Liquid 11 Wrench. 12 Q. Do any of the studies that are cited by what 13 -- well, before I get to that, what is your 14 understanding as far as the allegation that's being made 15 as to the way Mr. Cowey was exposed to benzene from this 16 product called Liquid Wrench. 17 A. Well, the allegations are that through his use 18 of Liquid Wrench under the conditions in which he 19 employed it, that the -- contamination of the product by 20 benzene provided him with an opportunity for exposure 21 through inhalation from his use of the product, and that 22 that exposure over time lead to the development of his 23 disease. 24 Q. Is it your understanding that there is some 25 claim also being made that he was exposed to the product Page 34 1 on his skin? 2 A. Yes. 3 Q. Do any of the studies that are cited by 4 Dr. Levy apply to that type of an exposure allegation; 5 that is to say, someone on a recreational basis using a 6 product like Liquid Wrench as Mr. Cowey describes using 7 it? 8 MR. LUBEL: Objection, form. 9 A. No. 10 Q. (BY MR. DILLARD) What do the studies cited by 11 Dr. Levy pertain to? 12 A. They pertain to exposure to solvents and mixed 13 solvents in an occupational setting, in different 14 occupational settings, involving the use of chemicals in 15 refinery situations, in situations associated with 16 making of shoes, in situations associated with exposure 17 to pure benzene in an occupational setting, exposure to 18 mixed solvents in a variety of different occupational 19 settings. 20 Q. Some involve pure benzene? 21 A. Yes. 22 Q. You mention the making of shoes. Which 23 particular study is that, that he -- that he, Levy, 24 refers to? 25 A. that The Aksoy -- the publications by Aksoy 1 deal with Turkish shoe workers involve exposure to 2 virtually neat or pure benzene used as a solvent in the 3 preparation of resins for making shoes. 4 Q. Are you familiar with those studies? 5 A. Yes. 6 Q. What type of a work environment were the 7 Turkish -8 A. Turkish shoe workers. 9 Q. -- shoe workers working in where they were 10 using this pure benzene? 11 A. It was primarily in home environments and 12 sweat-shop environments with -- in confined spaces, 13 either by families, or by groups of individuals, usually 14 groups of families, using benzene-based resins as a glue 15 for the manufacturing of shoes in poorly ventilated and 16 restricted areas. 17 Q. Do you recall what the general working 18 conditions were in terms of how many hours a day, and 19 that sort of thing? 20 A. The descriptions by Aksoy describe conditions 21 where people basically lived in those environments, 22 where they basically made these -- they made shoes, and 23 worked and were exposed to solvents in the agents they 24 were using virtually round the clock. They did this in 25 the home. So when they were working, when they weren't Page 35 1 working, they basically were living in and around the 2 materials that they were using. 3 Q. He cites -- he, Levy, cites a paper by Yin. 4 Are you familiar with that work? 5 A. Yes, I am. 6 Q. And what did that involve? 7 A. Yin did a virtual cross-sectional study of 8 exposure of workers in China to a variety -- in a 9 variety of settings, thousands of facilities and 10 hundreds of thousands of workers where benzene was not 11 directly measured but, in fact, the assessment of 12 exposure was made indirectly. 13 This involved, again, shoe workers. It 14 involved industrial workers, factory workers, petroleum 15 refinery workers, rubber workers, painters, a variety of 16 different occupational settings, usually involving quite 17 large facilities. 18 Q. Do you believe that that -- that Mr. Cowey's 19 alleged exposure scenario is comparable to the Aksoy or 20 the Yin studies? 21 MR. LUBEL: Objection, form. 22 Q. (BY MR. DILLARD) Do you have an opinion in 23 that regard? 24 A. My opinion is that the description of 25 Mr. Cowey's use of solvents in the course of his Page 36 Page 37 1 activities is not reflected or related to the types of 2 occupational exposure that has been the subject of these 3 studies. 4 Q. You also mentioned that some of the studies 5 that Dr. Levy cites, or other studies that Dr. Levy 6 cites, involve petrochemical plants? 7 A. Yes. 8 Q. Refineries? 9 A. Yes. 10 Q. Do you have an opinion as to whether or not 11 those studies would be applicable to the type of usage 12 that Mr. Cowey -- would the exposures in those studies 13 be comparable to Mr. Cowey's alleged use of the Liquid 14 Wrench product? 15 MR. LUBEL: Objection, form. 16 Q. (BY MR. DILLARD) Do you have an opinion in 17 that regard? 18 A. It's my opinion that those exposures are not 19 relevant to that of Mr. Cowey's. 20 Q. Looking back at the -- at the scientific rules 21 that you described for us earlier, another of the rules 22 you mentioned was specificity. With respect to 23 Mr. Cowey's alleged exposures to the Liquid Wrench 24 product, do the studies cited by Dr. Levy, in your 25 opinion, meet, or do they not meet the specificity 1 requirements? 2 A. They do not meet the specificity requirements. Page 38 3 Q. Why not? 4 A. They've looked at mixed solvent exposures, a 5 variety of different exposures, and do not quantitate 6 benzene exposure either in the context of mixed exposure 7 or potentially heavy exposure to pure benzene. So, from 8 the standpoint of providing a quantitative basis to 9 relate exposure or dose to the cause of disease, they do 10 not meet those criteria. 11 Q. You mentioned the consistency requirement of 12 the scientific rules. Do you have an opinion as to 13 whether or not Dr. Levy has satisfied that requirement? 14 MR. LUBEL: Objection, form. 15 A. He has not. In fact, as I mentioned, some of 16 the studies that he cites specifically with respect to 17 the question of the relationship between myelodysplastic 18 syndrome and exposure to solvents don't reach a 19 statistical -- don't provide evidence of a statistical 20 association between exposure and the development of the 21 disease. 22 Q. (BY MR. DILLARD) That's a point I want to ask 23 you about. Do some of the studies that Dr. Levy has 24 cited refer to or involve myelodysplastic syndrome -- 25 A. Yes, they do. Page 39 1 Q. -- the condition that Mr. Cowey has? 2 A. Yes, they do. 3 Q. And is there a consistency across those 4 studies that meets the scientific requirements? 5 A. No. Neither with respect to specificity or 6 consistency for those specific citations. 7 Q. With regard to the dose response requirement, 8 does Dr. Levy satisfy that requirement, in your opinion? 9 MR. LUBEL: Objection, form. 10 A. No, he does not. He does not address the 11 issue of dose. 12 Q. (BY MR. DILLARD) Okay. Let me ask it -- ask 13 it again. Does he even address the issue of dose 14 response in his opinions? 15 A. No, sir. 16 MR. LUBEL: Objection, form. 17 MR. RILEY: What's your objection basis 18 on that last question? 19 MR. DILLARD: Yeah. 20 MR. LUBEL: I'll tell you what primarily 21 my basis has been for a little while, which is Steve's 22 been referring to whether Dr. Levy has addressed certain 23 things, and he's not been specific to his report. And 24 as I appreciate what Dr. Irons is talking about, is what 25 is contained in his report. Steve's question doesn't Page 40 1 focus in on the report. It focuses in on what Dr. Levy 2 has addressed, when it would be speculation for one, 3 because neither Steve nor Dr. Irons have talked to 4 Dr. Levy about what he's done in this case. 5 MR. DILLARD: Well, that's not a form 6 objection. And I believe -7 MR. LUBEL: Well, maybe I am making a 8 poor objection but that's -- you asked for what I was 9 doing. 10 MR. DILLARD: That's not a form 11 objection. 12 MR. RILEY: True. 13 MR. DILLARD: But I appreciate the 14 clarification. We will certainly expect that he'll 15 remain hitched to the report he produced in this case, 16 since we've been required to produce reports, right? 17 Agree with me on that? 18 MR. LUBEL: Upon what? 19 MR. DILLARD: On that he has to stay -20 the subject matter he's covering is covered in his 21 report, right? 22 MR. LUBEL: I think by and large his 23 t i l th b t f hi 24 MR. DILLARD: Okay. 25 Q. (BY MR. DILLARD) Dr. Irons, let me a Page 41 1 you have an opinion, sir, whether or not -- first of 2 all, you're familiar with the opinions that Dr. Levy 3 expresses in his report; is that correct? 4 A. Yes. 5 Q. Okay. And that's his report dated -- what's 6 the date on it? 7 A. September 18th. 8 Q. It was produced to us by the plaintiffs, 9 pursuant to the requirements of the court back in 10 September. 11 In reviewing that report, do you have an 12 opinion whether or not Dr. Levy has ruled out with 13 reasonable certainty other factors that would explain 14 Mr. Cowey's disease? 15 A. Not at all. 16 Q. Why not? 17 A. Because the principal risk factor associated 18 with the development of myelodysplastic syndrome in the 19 vast majority of individuals is age, and that's not even 20 addressed in Dr. Levy's report. 21 Q. Let's talk for a moment about myelodysplastic 22 syndromes. How does the -- how does the disease get its 23 name, if you know? 24 A. Myelodysplastic syndrome is a relatively new 25 classification of diseases within the hemopoietic blood Page 42 1 forming system that's evolved over the past 30 years. 2 It is a neoplastic condition. It is a -3 Q. What does that mean? 4 A. It means that it is a cancer. 5 Q. Okay. 6 A. It is a type of cancer on a spectrum that 7 includes acute myelogenous leukemias, a specific 8 subclass of leukemias. So, myelodysplastic syndromes 9 and acute myelogenous leukemias represent a spectrum of 10 diseases that involve the altered maturation, growth, 11 and regulation of the cells of the bone marrow that make 12 our blood cells. 13 Q. Are all acute myelogenous leukemias considered 14 to be myelodysplastic syndrome? 15 A. No. 16 Q. Are all myelodysplastic syndromes considered 17 to be acute myelogenous leukemia? 18 A. No. As a matter of fact, the vast majority 19 are not. There is overlap in these diseases, but the 20 specific diseases within these classifications represent 21 distinct entities as defined by the scientific and 22 medical literature. 23 Q. Are there different forms of myelodysplastic 24 syndrome? 25 A. Yes. Page 43 1 Q. Can we refer to it as MDS? Is that an -2 A. Yes, MDS is -- is useful. 3 Q. How are cases of MDS diagnosed? 4 A. Cases of MDS are diagnosed using criteria and 5 techniques that are the same ones that are used in the 6 diagnosis of acute myelogenous leukemias. The basic 7 criterias in their -- there are three major components 8 to the laboratory diagnosis of these diseases. One is 9 to examine the cells and look at them to see what they 10 look like. It's called morphology. 11 So you look at the bone marrow, either in 12 smear or section, and evaluate what the cells in the 13 bone marrow look like. 14 Another is to use a technique that allows us 15 to look at a fingerprint of the molecules on the surface 16 of the cells that help us determine what they are, and 17 that's called immunophenotyping or flow cytometry. So 18 we're looking at fingerprinting on the surface, 19 morphology of the cells, what they look like, and also 20 we look at the DNA in these cells. We look at DNA to 21 see if there are structural changes in the DNA, and this 22 is what we talk about when we talk about chromosome or 23 chromosome abnormalities. Chromosomes are packets of 24 DNA, and if they are rearranged, absent or missing in 25 one form or another, this is also a criteria that's used Page 44 1 in the differential diagnosis of these diseases. 2 Q. Have you been -- you yourself been involved in 3 diagnosing these diseases? 4 A. Yes. 5 Q. As opposed to treating them like a doctor 6 would do? 7 A. I don't treat these diseases, but I diagnose 8 them and I supervise the laboratory that diagnoses them. 9 Q. With respect to the type of MDS that Mr. Cowey 10 is reported to have had, RCMD, is that a common or 11 uncommon form? 12 A. Very common. Probably the most common. It is 13 among the most common forms of MDS. 14 Q. And what -- what are the main risk factors for 15 MDS? 16 A. The principal risk factor for 85 percent of 17 the cases of MDS that are diagnosed is age. 18 Q. What's your understanding of the -- of the age 19 -- the peak age range when this disease is diagnosed? 20 A. Well, the data is fairly dramatic. Below the 21 age of 50, the incidence of MDS in the general 22 population is on the order of a half of a -- one to -- a 23 half to one or two per 100,000 people. At the age of 24 50, studies variously report an incidence of five to 25 maybe 12 per 100,000 people. And as you go up in Page 45 1 decade, it increases logarithmically. At the age 2 between 70 and 79, the incidence is on the order of 49 3 to 50 or even higher per 100,000. So, between the age 4 of 50 and the age of 80, you have a change that's about 5 ten-fold in terms of the incidence of the disease, and 6 above 80 it rises to 20-fold higher. 7 Q. So it continues to rise with increasing age? 8 A. Yes. 9 Q. What was Mr. Cowey's age when he was 10 diagnosed, if you recall? 11 A. I believe it was 72, 73, in that area. 12 Q. Would that be in a peak age range for this 13 disease? 14 A. Yes. Much higher than either the 50s or the 15 60s, obviously less than the 80s, or the 8th decade, but 16 extremely high. On the order of about 49 per 100,000. 17 Q. You were explaining this a moment ago, but 18 just very briefly, how does -- how does one tell one 19 form of MDS, say like the kind that Mr. Cowey has, from 20 another form? 21 A. With respect to Mr. Cowey's disease, the 22 issues that are important are the types of cells that 23 are present by morphology, so the number of blast cells 24 that are present in the bone marrow; as well as data 25 from flow cytometry or immunophenotyping looking at Page 46 1 molecules on the surface of the cells; and also 2 cytogenetics, genetics, looking at chromosomes, and 3 changes in the DNA. 4 Q. Are you familiar from reviewing Mr. Cowey's 5 medical records as to whether he had any particular 6 chromosome pattern that was found when his was 7 diagnosed? 8 A. Yes. He had three of the cells that were 9 examined for cellular genetic damage or chromosome 10 aberrations, possessed an extra chromosome 8, which is 11 referred to as trisomy 8. And the fact that it was 12 found in three cells establishes that it is a clonal 13 lesion, and is most likely associated with the 14 development of his disease. 15 Q. Do you have an opinion as to whether 16 Mr. Cowey's chromosome pattern, this trisomy 8, would 17 fit into the pattern seen in the 85 percent of MDS cases 18 where the cause is not known as opposed to the 15 19 percent of cases where it is? 20 A. The pattern of presentation of his disease, 21 including trisomy 8, is a pattern that's most frequently 22 found in the 85 percent for which we -- there's no known 23 cause, or that's commonly called idiopathic MDS; and is 24 much less frequently found, in fact, is rare, in cases 25 of MDS that have -- that are known to be associated with Page 47 1 other causes. 2 Q. The 15 percent? 3 A. Yes. And that -- that particular pattern has 4 become increasingly prominent over the last several 5 years, and certainly the most recent literature looking 6 at the development of MDS occurring secondary to 7 exposure to toxic agents, the -- there's a clear deficit 8 or rarity of trisomy 8 in those cases. 9 MR. LUBEL: Objection, nonresponsive. 10 Q. (BY MR. DILLARD) Do you have some published 11 literature, peer-reviewed literature, that you have here 12 with you today that supports the opinions that you've 13 expressed? 14 A. Yes. 15 Q. You said that this was becoming more 16 increasing -- excuse me, that this was increasingly 17 becoming known in the literature in the last few years. 18 What specifically are you talking about? 19 A. Well, for example, in the early '90s, it was 20 well recognized that there were patterns of chromosome 21 abnormalities that were found in acute myelogenous 22 leukemia, AML and MDS, that was associated with exposure 23 to toxic agents that were clearly more likely to be 24 found in those cases than in idiopathic cases. 25 Q. And what -- Page 48 1 A. The majority of cases. 2 Q. What does idiopathic mean? 3 A. No known cause. 4 At the same time there are chromosome 5 abnormalities that were reported occasionally occurring 6 in either, those that were idiopathic, no known cause; 7 or those that developed secondary to exposure to toxic 8 agents. 9 Q. Such as what -10 MR. LUBEL: Objection, nonresponsive. 11 Q. (BY MR. DILLARD) -- type of toxic agents? 12 A. Alkylating chemotherapeutic agents, radiation. 13 Q. Cancer drugs? 14 A. Cancer drugs. 15 Q. Radiation? 16 A. Radiation. Also, in solvent exposure where 17 these lesions have been found in individuals who have 18 been occupationally exposed to solvents, including 19 benzene. 20 Q. Now, is that -- is that group, the 21 chemotherapy, the radiation, and the benzene exposure, 22 is that the 85 percent category or is that the 15 23 percent? 24 A. That's the 15 percent category. 25 Q. All right. Page 49 1 A. What we've seen over the last several years 2 with increasing -- with studies that look at larger 3 numbers and have focused on primarily the 4 chemotherapeutic literature, it's become clear that this 5 difference in the pattern of the frequency of chromosome 6 abnormalities that are seen in those developing 7 secondary to exposure and those that are idiopathic is 8 much greater than was considered in the past. So, we 9 now have recent studies looking at very large numbers of 10 cases where that pattern of differences in the types of 11 chromosome lesions that are found between those exposed 12 to alkylating agents and those that are not is a 13 dramatic difference. 14 MR. LUBEL: Objection, nonresponsive 15 Q. (BY MR. DILLARD) What is the predominant 16 pattern that is seen in the 85 percent of cases where 17 age is the risk factor and there's no known external 18 cause? 19 MR. LUBEL: Objection, form. 20 21 there? 22 MR. DILLARD: What's the form objection MR. LUBEL: Compound. Age is the risk 23 factor and there is no external cause. 24 Q. (BY MR. DILLARD) Okay. What is the 25 predominant pattern that is seen in the 85 -- first of Page 50 1 all, let's go back to the 85 percent of cases. 2 Is this the group where there is a known risk 3 factor or -- excuse me, where there is a known cause or 4 not a known cause? 5 A. Not a known cause. 6 Q. Okay. And what's the main risk factor in that 7 group? 8 A. Age. 9 Q. All right. What is the predominant chromosome 10 pattern that is seen in that category? 11 A. Reoccurring chromosome lesions that are found 12 and described in acute myelogenous leukemia and in MDS 13 that are associated with no known cause; and there are a 14 series of reoccurring lesions that are described in the 15 diagnostic classification of these, included among them 16 would be trisomy 8, or involvement of translocations 17 involving chromosome 8. Also, other types of 18 abnormalities as well, most of them involving 19 translocations or inversions. 20 Q. Now, let's talk about the 15 percent category, 21 where there's a known cause. What's the predominant 22 pattern that is seen in those? 23 A. The predominant pattern is the loss of all or 24 part of chromosome 5 and/or chromosome 7 and sometimes 25 both; so involving the chromosome 5 and chromosome 7 and Page 51 1 deletions of those chromosomes. And studies over the 2 years suggest that the incidence of those in AML and MDS 3 preceding AML following exposure to alkylating agents is 4 higher than 70 percent. The most recent study by Larson 5 in Chicago suggests 76 percent. 6 Q. Did James Cowey have that chromosome pattern? 7 A. No, he did not. 8 Q. Is the MDS that is in this 85 percent category 9 considered to be the same disease or a different disease 10 from the MDS in the 15 percent category? 11 A. The World Health Organization classification 12 of diseases, which has become the world bench standard 13 for the classification of these over the last couple of 14 years, distinguishes MDS into several different 15 categories; and it distinguishes AML, acute myelogenous 16 leukemia, into several different categories. The 17 specific type of AML associated with exposure to 18 alkylating agents is preceded by a type of MDS, and so 19 the -- they're referred to together as MDS/AML 20 developing secondary to exposure to these agents. So it 21 has a specific disease classification all by itself. 22 Q. Is that the same as or different from -23 A. It's different from. 24 Q. -- the 85 percent? 25 A. That's correct. 1 Q. Incidentally, did you note the treatment that 2 Mr. Cowey had received, the medication that he had 3 received? 4 A. Yes. 5 Q. Okay. What did he -- what did he receive? 6 A. He was entered into an experimental protocol 7 that involved the use of a derivative of 8 Dideoxycytidine, 5-Aza-2'-Deoxycytidine, and Cytosine 9 Arabinoside, or Ara-C. Ara-C is routinely used in 10 treating myelodysplasia and acute myelogenous leukemia, 11 usually in combination with other drugs. In this 12 particular case, the use of the Dideoxycytidine 13 derivative was an experimental protocol. 14 Q. Have you had any involvement with that drug? 15 A. Yes. I worked on the development of the 16 parent compound Dideoxycytidine, 2'3'-Dideoxycytidine, 17 prior to its approval as a drug. 18 Q. Have you published on that drug? 19 A. Yes, I have. 20 Q. Do you have that paper here with you in the 21 event someone wants to ask you questions about it? 22 A. Yes, I do. 23 Q. Do you also have here available the papers 24 that you referred to earlier involving this 85 percent 25 category and the chromosome pattern seen there, and the Page 52 Page 53 1 15 percent category and the chromosome pattern seen 2 there? 3 A. Yes. 4 Q. Let me turn now to the last of the subjects 5 that you were asked to address, Dr. Irons, and if you 6 could remind us again what that was. 7 A. Specifically with respect to the probability 8 that Mr. Cowey's disease was caused by his exposure to 9 benzene over the years in his use of Liquid Wrench. 10 Q. Applying the scientific methodology that 11 you've described, do you have an opinion as to whether 12 there is reliable scientific evidence that Mr. Cowey's 13 use of Liquid Wrench, assuming it contained benzene for 14 purposes of this question, was a cause of his disease? 15 A. Yes, I do. 16 Q. And what is that opinion? 17 A. That there is no reliable scientific basis to 18 conclude that his exposure to benzene Liquid Wrench was 19 the cause of his myelodysplasia. 20 Q. Why do you say that? 21 A. First of all, because the presentation of his 22 myelodysplasia, as I've just said, is consistent with 23 presentation that's seen in vast majority of individuals 24 who develop idiopathic myelodysplastic syndrome, the 25 major risk factor of which is age, and his age at Page 54 1 diagnosis is consistent with that. 2 Independently, there's no basis upon which 3 the information I have been provided with that I can 4 quantitate a -- make a meaningful assessment of his 5 exposure to benzene, given the information that's been 6 presented to me. So, it's impossible for me to provide 7 a quantitative analysis of his exposure to benzene. 8 Independent of that, the quantitative 9 epidemiologic literature that demonstrates an 10 association between exposure to benzene and the 11 development of AML or MDS involves exposure scenarios 12 and occupations that are not relevant to Mr. Cowey's 13 specific situation and use of the product Liquid Wrench. 14 Q. Assuming that he was last using Liquid Wrench 15 at a time when it might have contained benzene, in 1978, 16 and his diagnosis was in 2001, do you have an opinion as 17 to whether or not that would be consistent with the 18 Liquid Wrench usage explaining his disease? 19 A. The vast majority of the quantitative 20 epidemiology -- epidemiologic literature dealing with 21 the development of acute myelogenous leukemia following 22 exposure to benzene defines a latency, or period, or 23 interval between opportunity for exposure and 24 development of disease that has a median of about 25 nine-and-a-half to ten years. More recent follow-up Page 55 1 studies of those same populations suggest that it may be 2 possible that that latency may extend for a period of, 3 say, 15 years at the latest, or the longest. But I know 4 of no basis to conclude that on -- certainly on the 5 basis of latency that exposures exceeding that, or 6 certainly exceeding 20 years, are associated with the 7 development of acute myelogenous leukemia. 8 Q. How about MDS? 9 A. MDS is subsumed within diagnosis of AML when 10 we're talking about AML secondary to exposure to toxic 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 agents. They're part of the same paradigm or process. Again, in contrast, if you look at MDS/AML developing secondary to alkylating chemotherapy, the latency interval is on the order of two to seven years. MR. LUBEL: Objection, nonresponsive. Q. (BY MR. DILLARD) What is the latency period for the development of the MDS/AML disease that is at -that's this 15 percent, what is the latency in those individuals receiving chemotherapy? A. Two to seven years. Q. Do you have an opinion as to the most likely factor in explaining Mr. Cowey's disease? A. His age. MR. DILLARD: Thank you, sir. I think that's all the questions I have right 1 now. 2 EXAMINATION Page 56 3 BY MR. LUBEL: 4 Q. Dr. Irons, my name is Lance Lubel, and you and 5 I briefly met right before we started this deposition, 6 correct? 7 A. That's correct. 8 Q. We had never met before? 9 A. That's correct. 10 Q. True? And as I appreciate it, you have been 11 retained by the lawyers for United States Steel 12 Corporation to serve as an expert witness for them, 13 that true? 14 A. That's correct. is 15 Q. When were you retained? 16 A. I believe it was this summer, may have been 17 August. 18 Q. Mr. Steve Dillard from the law firm of 19 Fulbright and Jaworski, did you have discussions with 20 him about this? 21 A. I had discussions with Mr. Dillard and with 22 Mr. Kemp. Kemp. 23 Q. Another lawyer from their Dallas office? 24 A. I believe so, yes. 25 Q. Is -- is benzene a carcinogen, in your Page 57 1 opinion? 2 A. Yes. 3 Q. What does the term carcinogen mean? 4 A. That it is a substance or chemical or an agent 5 that can cause certain types of cancer. 6 Q. If I heard you correctly when Mr. Dillard from 7 Fulbright was asking you questions, I believe that you 8 said that MDS, or myelodysplastic syndrome, was a 9 cancer, in your opinion? 10 A. Yes. It is a neoplastic disease. It is by 11 definition clonal, which means it is a cancer. 12 Q. Is there any dispute amongst good scientists 13 such as yourself as to whether benzene is, in fact, a 14 cancer-causing agent? 15 A. No. 16 Q. Would it be fair to say that it is generally 17 accepted in both the medical and the scientific 18 community that benzene can cause cancer if exposures are 19 correct? 20 A. If the exposures are sufficient, benzene has 21 been demonstrated to cause specific kinds of human 22 cancer, principally the acute myelogenous leukemias. 23 Q. And, in fact, sir, is it true that benzene has 24 been known in the medical and scientific community to 25 cause serious -- or can cause serious health 1 consequences for many, many decades? Page 58 2 A. Certainly since the -- benzene's been known 3 for many, many years to be -- to be able to cause bone 4 marrow suppression, and toxicity to the blood forming 5 organs. Certainly, by the mid '70s, the mid to late 6 '70s, it was generally appreciated and understood that 7 benzene could also cause acute myelogenous leukemia. 8 Q. Are you aware, Dr. Irons, from all of your 9 research regarding benzene, that adverse health 10 consequences have been reported in the literature back 11 in the 1920s and '30s regarding benzene exposures? 12 A. Yes. 13 Q. And, in fact, I am sure you're aware, and 14 since you have been in this field for some period of 15 time, that the American Petroleum Institute that was 16 made of large oil companies such as United States Steel 17 Corporation, that they issued a report in about 1948 18 that found that benzene was a hazardous substance. 19 MR. DILLARD: Object to the form of the 20 question. 21 Q. (BY MR. LUBEL) Are you aware of that, sir? 22 A. I'm generally aware that the American 23 Petroleum Institute recognized the potential toxicity of 24 benzene, certainly as early as the '40s. 25 Q. And you have no reason to dispute that -- that 1 companies that were interested in finding out what the 2 potential hazardous health effects from benzene exposure 3 were, that there was some information that was available 4 as early as the 40s concerning benzene exposures, true? 5 MR. RILEY: Objection, form. 6 A. As a matter of fact, there were several 7 anecdotal reports going back at least that far, that 8 described bone marrow suppression and the development of 9 blood disease associated with very high level exposure 10 to benzene. 11 Q. (BY MR. LUBEL) And I'm sure that you're aware 12 that the 1948 report by the American Petroleum Institute 13 was actually authored by a gentleman from the Harvard 14 Medical School by the name of Dr. Phillip Drinker? 15 A. That I couldn't tell you one way or the other. 16 Q. Do you know who Dr. Drinker is or was? 17 A. He was a prominent hematologist, I believe. 18 Q. He was a good and reputable doctor in his 19 field of blood disorders, correct? 20 A. To my understanding, yes. I wasn't there at 21 the time. 22 Q. But -23 A. Yes, he's well-known. 24 Q. In your years of researching and writing on 25 the topic of benzene exposures, you've come across Page 59 Page 60 1 Dr. Drinker's name on more than one occasion, I take it? 2 A. Yes. 3 Q. And he's well written in that area, true? 4 A. Yes. 5 Q. And were you aware that the 1948 American 6 Petroleum Institute study that Dr. Drinker authored on 7 behalf of oil companies stated that there was -- there 8 was absolutely no safe level of benzene exposure? 9 A. I do recall that it said that. 10 Q. And, in fact, you acknowledge that that study 11 talked about blood and blood forming disorders, correct? 12 A. Yes. 13 Q. And would you agree that MDS, the disease that 14 you acknowledge Mr. Cowey has, is a blood or blood 15 forming disorder? 16 A. It is. It's probably important to point out 17 that at that particular point in time, the 18 state-of-the-art was such that myelodysplastic syndrome 19 wasn't recognized as a disease process, and that the 20 exposures that were at issue with respect to the 21 toxicity of benzene in the '40s were several fold higher 22 than those that we now are concerned about with respect 23 to benzene exposure and toxicity. 24 MR. LUBEL: I object to everything after 25 "It is" as being nonresponsive. Page 61 1 Q. (BY MR. LUBEL) Have you brought with you, 2 Dr. Irons, the peer-reviewed published articles that 3 state that there are -- there -- there is a safe level 4 of benzene exposure? 5 A. I am not sure what you're referring to. 6 Q. Well, we talked just a minute ago briefly 7 about the American Petroleum Institute study in 1948 8 that said there was absolutely no safe level of benzene 9 exposure, short of zero. And so my question is: Have 10 you brought with you today any peer-reviewed published 11 literature that tells us what the safe level is? 12 A. There is no literature that I can point to, 13 including the API report, which incidentally wasn't a 14 peer-reviewed study either, that defines a safe level. 15 There are many studies that in the context of 16 quantifying the relationship between exposure and 17 disease, that have provided a characterization of dose 18 response. But in science we can't prove a negative; and 19 therefore, you won't find any studies that point to a 20 specific level and say that it is safe. That's not 21 something that science does. 22 Q. So, you don't have, at least with you today, a 23 study that says what level of exposure to benzene is 24 considered safe by the relevant medical and scientific 25 community, correct? 1 A. As I said, in science we can't prove a 2 negative, so there are no studies that exist that will 3 affirmatively say that there is a quantitative level 4 that has been proven to be safe. 5 Q. So, the information that was published in the 6 1948 American Petroleum Institute, where they said that 7 there is absolutely no safe level of benzene exposure, 8 that still holds true today, correct? 9 A. No. I don't believe so. I don't believe that 10 you can say there's absolutely no level that does not 11 produce adverse health effects. There clearly are. But 12 pointing to a specific level and saying that there is a 13 study or a body of literature that states that this 14 level is safe is not something that scientists do. 15 Q. What are the accepted risk factors of MDS, 16 Mr. Cowey's disease? And by accepted I mean generally 17 accepted in your field, medical people and scientists. 18 MR. DILLARD: I'm sorry, would you state 19 it again? 20 Q. (BY MR. LUBEL) I'll be happy to. What are 21 considered to be in your community, the medical and 22 scientific community, the generally accepted risk 23 factors for MDS, myelodysplastic syndrome? 24 A. Depending upon the specific type of 25 myelodysplastic syndrome, as I have -- as I've discussed Page 62 Page 63 1 previous today, the risk factors include age, which is 2 the predominant risk factor certainly for idiopathic 3 myelodysplastic syndrome. With respect to MDS 4 developing in the context of acute myelogenous leukemia, 5 or in combination of acute myelogenous leukemia, 6 exposure to alkylating chemotherapeutic agents, exposure 7 to radiation, and with some controversy, exposure to 8 benzene. 9 There are other agents that have been 10 generally -- other agents and drugs that have been 11 variously suggested to be associated with it, but in 12 general those are the major causes. 13 Q. Well, other than age, exposure to alkylating 14 agents, which I think you've referred to as basically 15 chemotherapy? 16 A. Yes. 17 Q. Radiation is accepted, true? 18 A. Yes. 19 Q. True? 20 A. Yes. 21 Q. And is that ionizing radiation? 22 A. Yes, definitely. 23 Q. And then certain benzene exposures? 24 A. There -- there's at least one report that 25 implies electromagnetic radiation. That certainly has 1 not been confirmed and has not been demonstrated with 2 respect to biologically plausible mechanisms. 3 Q. So, as you sit here today, do you have the 4 opinion that electromagnetic exposures -- is that what 5 you referred to it as? Electromagnetic -6 A. Electromagnetic fields. 7 Q. At this point in time, as you sit here, is the 8 information sufficient for scientists such as yourself 9 to conclude that that causes MDS? 10 A. No. 11 Q. And as you sit here today, are you aware of 12 any exposures that Mr. Cowey had to electromagnetic 13 fields? 14 A. No. 15 Q. So, other than age, chemotherapy, ionizing 16 radiation, and benzene, are you offering any opinions as 17 to the major accepted risk factors for MDS other than 18 those? Page 64 19 A. No. 20 Q. How much benzene was Mr. Cowey exposed to -21 MR. DILLARD: Object to -22 Q (BY MR. LUBEL) -- during his lifetime? 23 MR. DILLARD: Object to the form. 24 A. I don't know. 25 Q. (BY MR. LUBEL) How many years did Mr. Cowey Page 65 1 use benzene-containing products? 2 MR. DILLARD: Object to the form. 3 A. As a toxicologist, the only responsible answer 4 I can give to that is as long as he worked, he was 5 exposed to products that to some degree or some form 6 contained benzene because it's ubiquitous. You can't 7 exclude for -- assume that at any time he or any of the 8 rest of us have not had some exposure to benzene. 9 Q. (BY MR. LUBEL) But as you sit here today, can 10 you offer to the jury, based upon the information that 11 the United States steel lawyers have provided you, 12 either on a qualitative basis or quantitative basis, 13 what Mr. Cowey's exposures to benzene were over his 14 lifetime? 15 A. No, I can't. 16 Q. Did -- did the lawyers for United States Steel 17 Corporation advise you that on a fairly regular basis 18 Mr. Cowey used benzene-containing products for 19 approximately 25 years? 20 MR. DILLARD: Object to the form. 21 MR. RILEY: Same objection. 22 A. I am aware and was provided with information 23 that related to the allegation that he had used Liquid 24 Wrench, and Liquid Wrench is a solvent mixture. 25 Q. that (BY MR. LUBEL) But did they tell you 1 there was benzene as an ingredient in that product? Page 66 2 A. I have seen reports that document that at 3 various times the product contained mixtures of 4 raffinates that included some benzene, yes. 5 Q. And that varied, based upon the information 6 you were provided? Would you agree with that? 7 A. Yes. 8 Q. Not every batch was exactly the same, true? 9 A. That's correct. 10 Q. And that wouldn't surprise you as a scientist? 11 A. No. 12 Q. Have you done work for any Exxon or Mobil 13 entities during your career as a scientist? 14 A. I've consulted with Exxon before. 15 Q. Have you done any work for Mobil? 16 A. Yes, I believe so. 17 Q. And did you find your experience with the 18 Mobil people to be enlightening? 19 MR. DILLARD: Object to the form. 20 A. I'm afraid I don't know what you mean. 21 Q. (BY MR. LUBEL) Let me tell you what I'm 22 driving at, Dr. Irons. 23 The lawyers in this case have -- have seen 24 studies performed by Mobil employees that demonstrate 25 that Liquid Wrench, at least in the late '70s, had a Page 67 1 benzene content of 7 to 30 percent. Have you seen those 2 studies? 3 MR. RILEY: Objection, form. 4 A. I've seen references to analysis of raffinate 5 in at least one occasion that would comport with those 6 -- that level of benzene. 7 Q. (BY MR. LUBEL) And I am trying to be more 8 specific. As you -- you understand that raffinate is a 9 component of Liquid Wrench, correct? 10 A. Yes. 11 Q. What I'm telling you is, is that the lawyers 12 in this case have been provided Mobil documents that 13 indicate that Liquid Wrench itself had a benzene content 14 between 7 percent and 30 percent, and I am asking you if 15 you have seen those? 16 A. What I -- what I recall seeing is the -- is 17 various anal -- various analyses of raffinate in at 18 least one occasion that would be consistent with those 19 levels. 20 Q. Do you have any reason to disagree or differ 21 with what those documents tell us about the benzene 22 component of Liquid Wrench? 23 A. No. 24 Q. There was a period of time where you did work 25 for the -- I think you called it the Chemical Industry KC' 1 Institute of Toxicology? 2 A. Yes. Page 68 3 Q. Where were they based? 4 A. Research Triangle Park, North Carolina. 5 Q. And who owned that group, if you will? 6 A. It was a nonprofit independent research 7 institute that conducted research on commodity -- 8 toxicology, research on commodity chemicals. It was 9 funded when I was there through a group of chemical 10 companies. 11 Q. Do you know the name of those chemical 12 companies? 13 A. There was something like 20 or 23. I know 14 some of them but I certainly couldn't give you an 15 exhaustive list. 16 Q. Just tell me the ones you can remember. 17 A. Dow, Dupont, Exxon, Mobil, Chevron, Conoco, 18 W. R. Grace, Phillips -- I don't know what number I'm at 19 -- Shell, Monsanto, many different companies. 20 Q. When did you do work for -- for those 21 companies? 22 A. I worked for the Chemical Industry Institute. 23 I didn't work for the companies. 24 Q. That's what I mean. What -- what time period 25 are we talking about? Page 69 1 A. 1977 to 1987, '88. 2 Q. And I take it during this roughly -- that's a 3 ten-year period, am I right? 4 A. Yes. 5 Q. -- that you would have fairly frequent 6 communication with representatives of these various 7 chemical companies you've told us about, correct? 8 A. Only within the context of restrictions that 9 the Institute guidelines placed on me. We did not have 10 routine interaction with company representatives outside 11 of the normal activities of the institute. 12 Q. Were you aware that Mr. Dillard and his law 13 firm of Fulbright & Jaworski do a lot of work for those 14 companies? 15 A. At that time -16 MR. DILLARD: Object to the form. 17 A. -- no, I didn't know Mr. Dillard then. 18 Q. (BY MR. LUBEL) Talking about now. Are you 19 aware of it as you sit here now? 20 MR. DILLARD: Object to the form. It's 21 not right, but -22 A. For which companies? 23 Q. (BY MR. LUBEL) Well, when did you meet 24 Mr. Dillard? 25 A. Probably I first met Mr. Dillard 1989, 1990, 1 1991, somewhere in that time frame. Page 70 2 Q. And how did you meet him? 3 A. I don't remember the first time I met him. It 4 might have been in conjunction with a lawsuit in which I 5 was an expert, but I couldn't tell you specifically the 6 first time I met him. 7 Q. Do you recall that -- at any rate that it was 8 a lawsuit that had something to do with chemical 9 exposures? 10 A. If it was a lawsuit, I -- I think that would 11 be safe assumption. 12 Q. And has it been your experience since you've 13 been doing work for Mr. Dillard that oftentimes he 14 represents chemical companies? 15 A. Yes. 16 Q. Have you ever been an expert witness for 17 Mr. Dillard or his law firm in cases where they did not 18 represent a chemical company? 19 A. I don't believe so. 20 Q. Now, when were you first introduced to 21 litigation? 22 A. 1989, I believe. 23 Q. And who was the first person that introduced 24 you to lawsuits and potential expert work you could 25 provide in that area? Page 71 1 A. Well, the first attorney that I ever agreed to 2 talk to on this would have been Mr. Robert Scott. 3 Q. And who put y'all two together as you 4 appreciate it? 5 A. He called me. 6 Q. And did he tell you who he got your name from? 7 A. Got my name, I believe, from Dr. Daniel 8 Teitelbaum. 9 Q. And who is Dr. Daniel Teitelbaum? 10 A. He's a toxicologist in Denver. 11 Q. He does similar work to you, similar field? 12 A. I think that's probably a stretch, but he -13 he's involved primarily -- I think his background is in 14 drug abuse and toxicity of drugs and glues and things 15 like that. 16 Q. Is he a good doctor? 17 A. I have no idea. 18 Q. Have you met him before? 19 A. Yes, I have. 20 Q. Is he reputable in his field? 21 A. I'm not sure how you would define his field 22 I really can't speak to what his reputation is as a 23 doctor. 24 Q. So, tell me what you can recall about your 25 first conversation with Mr. Robert Scott, about you Page 72 1 getting involved in these lawsuits. 2 A. I think it's -3 MR. DILLARD: Object to the form. 4 A. At the time, as I recall, he asked me if I 5 knew that my work, my research, was being used to 6 support opinions that were being offered in litigation; 7 and I said, no, I wasn't. And he asked me to -- if I 8 would take a look at some testimony and call him back if 9 I felt like it, and send him a bill otherwise. But 10 simply just to review testimony that had been presented 11 in a case relating to my own work, and the 12 interpretation of that work, and after some give and 13 take I agreed to do that. 14 Q. (BY MR. LUBEL) Did you at some point in time 15 learn that Mr. Robert Scott, in fact, represents 16 companies similar to Mr. Dillard and his law firm; that 17 is, chemical companies? 18 MR. RILEY: Objection, form. 19 A. Mr. Scott asked me if I would be willing to 20 serve as an expert in a case that involved the 21 allegation of disease caused by exposure to benzene. 22 Q. (BY MR. LUBEL) My question is -- it's a 23 little bit more specific, and that is at some point in 24 your time -- in time, did you learn that Mr. Scott, like 25 Mr. Dillard, typically represents chemical companies in Page 73 1 these chemical exposure cases? 2 MR. RILEY: Objection, form. 3 A. I think he does. He represents a number of 4 clients, some of which include chemical companies. 5 Q. (BY MR. LUBEL) Can you think of any clients 6 that Mr. Scott has had in the number of cases that 7 you've worked with him on, where he represented 8 companies that were not in the chemical company field, 9 if you will? 10 A. It's my understanding -- I know that he has 11 been involved and has represented companies that aren't 12 chemical companies, but I couldn't tell you in which 13 particular cases or who they are. 14 Q. Dr. Irons, do you hold yourself out as an 15 expert epidemiologist? 16 A. No. I'm a toxicologist. 17 Q. And what is the difference between toxicology 18 and epidemiology? 19 A. Epidemiology is the science that deals with 20 the design and conduct of population-based studies 21 relating to the cause of disease and the incidence of 22 disease. 23 It's distinguished from toxicology in that 24 toxicology is primarily focused on understanding the 25 specific relationships and pathogenesis of disease Page 74 1 caused by exposure to chemicals. Toxicology uses 2 epidemiology extensively in evaluating the cause of 3 disease. 4 Q. Are you a hematologist? 5 A. I'm an experimental hematologist, and I'm a 6 clinical laboratory scientist that uses hematology in 7 differential diagnosis. 8 Q. Do you hold yourself out as a hematologist? 9 A. Yes. As an experimental hematologist, I do. 10 Q. Now, is there a difference between a medical 11 doctor hematologist and an experimental hematologist? 12 A. Yes. 13 Q. What is the difference? 14 A. A medical doctor as a hematologist is involved 15 in the treatment of diseases involving the blood system. 16 I am not involved in the treatment of blood diseases. 17 An experimental hematologist is an individual who is 18 concerned with the understanding the mechanisms of 19 diseases involving the blood forming organ. 20 Q. Now, if I understood you correctly, you're not 21 a medical doctor, correct? 22 A. That's correct. 23 Q. And you did not go through a complete -- all 24 the courses that medical students have to go through, 25 correct? Page 75 1 A. That's correct. 2 Q. And you don't hold yourself out as an expert 3 in -- as a physician? 4 A. No. 5 Q. Is that true? 6 A. That's correct. 7 Q. Now, if I heard you correct, the work that 8 you're doing over in China is funded by some chemical 9 companies, too; is that correct? 10 A. It's -- it's funded by a consortium that is 11 made up of companies that are involved in petroleum. 12 Q. Okay. And there's a difference between -- at 13 least in your mind between petroleum companies and 14 chemical companies? 15 A. In general, yes. 16 Q. But your work even in China that you talked to 17 the jury about so far today is being funded by petroleum 18 companies? 19 A. That's correct. 20 Q. So, would it be fair to say that between 1977 21 through roughly today, in 2003, that much of your work 22 has been funded by either the chemical or the 23 petrochemical industry? 24 A. A great deal of it has. A great deal has also 25 been supported by federal funds and pharmaceutical 1 companies, and a variety of other sponsors. Certainly Page 76 2 because my focus and focus of my research is -- involves 3 primarily drugs and chemicals, much of my research 4 funding has come from the makers of those products. 5 Q. And I didn't mean to imply that you have not 6 done any other work in your career as a scientist other 7 than for the chemical and the petrochemical industry. 8 My only point was much of your work has been funded by 9 those industries? Is that true? 10 A. That's correct. 11 Q. Now, I am curious, because in your report, and 12 I have seen a report -- is your report dated October 13 24th of 2003? 14 A. Let me look at the date here. Yes, it is. 15 Q. In your report, it's a number of pages, you -- 16 you do make some opinions based upon Mr. Cowey's 17 exposures within the report, is that a fair statement? 18 A. I make some opinions on exposure that are 19 based upon a report that I reviewed by Mr. Spencer. 20 Q. All right. Now, I think what you've told me 21 so far, I want to make sure we're on the same page, is 22 that you don't feel as you sit here today that you have 23 seen competent evidence, if you will, or proof, of what 24 Mr. Cowey's exposures to benzene or benzene-containing 25 products has been throughout his life, is that a fair 1 assessment? Page 77 2 A. No. Not exactly. Based on the materials that 3 I've reviewed in this case, I cannot make a reasonable 4 quantitative assessment of what his exposure was. I did 5 review Mr. Spencer's report which provided me with a 6 worst-case scenario, and I did reach a conclusion based 7 upon that with respect to given a worst-case scenario, 8 what, in fact, the relationship would have been between 9 Mr. Cowey's exposure to benzene and potential 10 development of his disease. 11 Q. And that's what I want to visit with you about 12 for -- for a moment is the report that you relied upon 13 that Mr. Spencer provided you. Do you have that with 14 you? 15 MR. RILEY: Objection, form. 16 A. I don't know whether I do or not. 17 MR. LUBEL: We're going to take a short 18 break, Dr. Irons, and if -- I am n o t s a y i n g y o u c a n ' t d o 19 anything else; but over the break, will you look for 20 that report? 21 THE WITNESS: Yes. 22 MR. LUBEL: Thank you. 23 THE VIDEOGRAPHER: Going off the record. 24 Time is approximately 11:41 a.m. 25 (A break was taken.) 1 THE VIDEOGRAPHER: This is the beginning 2 of tape 2. The time is approximately 11:55 a.m. We're 3 now back on the record. 4 Q. (BY MR. LUBEL) Dr. Irons, before we took the 5 break, I asked you to try and locate the Mr. Spencer 6 report that you -- that you've addressed earlier, 7 correct? 8 A. Yes. 9 Q. Did you find it? 10 A. Yes, I did. 11 Q. What product did Mr. Spencer test? 12 A. Liquid Wrench, I believe. 13 Q. And do you know if the components of the 14 Liquid Wrench that he tested were the components in the 15 Liquid Wrench that Mr. Cowey used? 16 A. I can't say that on the basis of my review of 17 the report. 18 Q. Can you tell if the product called Liquid 19 Wrench that Mr. Spencer tested was a 2003 product? 20 A. No. I have no idea. 21 Q. Do you see the reference in Mr. Spencer's 22 report about how he added benzene or had benzene added 23 to the Liquid Wrench product? 24 A. Certainly -- well, what I have is the amounts 25 that were -- were in the formulations. I don't know Page 78 Page 79 1 exactly how he compounded those. 2 Q. But, as you sit here today as an expert 3 witness for United States Steel Corporation, you can't 4 tell us under oath whether or not the product that 5 Mr. Spencer tested was in fact a product that had the 6 same or substantially similar ingredients to that that 7 Mr. Cowey used, correct? 8 A. I can't say that. No. 9 Q. And I take it that it's -- there's those kind 10 of deficiencies, if you will, or shortcomings, in 11 Mr. Spencer's report that have put you in a position to 12 say, I don't have any meaningful information, I think is 13 the word you used, or I can't make a meaningful 14 evaluation of Mr. Cowey's benzene exposures? 15 MR. DILLARD: Object to the form of the 16 question. 17 Q. (BY MR. LUBEL) Is that what you said? 18 MR. DILLARD: Object to that question. 19 A. I reviewed this report and I've reviewed the 20 testimony of Dr. Rose, and Dr. Rose's testimony provides 21 me with absolutely no basis or quantitation or estimate 22 of what Mr. Cowey's exposure to benzene might have been. 23 Mr. Spencer's report is a -- is to my understanding an 24 estimate of worst-case exposure scenario based upon the 25 modeling conditions that he used in deriving this Page 80 1 report. So, I have independently used these numbers in 2 evaluating worst-case scenario for potential exposure. 3 But I have seen, in certainly Dr. Rose's report, no 4 information, nor in Mr. Spencer's report, information 5 that would allow me to evaluate specifically what 6 Mr. Cowey's personal exposure would have been. 7 MR. LUBEL: Objection, nonresponsive 8 Q. (BY MR. LUBEL) Did you earlier today in your 9 testimony make a statement that you didn't feel as 10 though you were in a position to make a meaningful 11 evaluation of Mr. Cowey's benzene exposures based upon 12 the information that had been provided to you? 13 A. That's correct. 14 Q. Do you stick by that statement now that I'm 15 asking you questions? 16 A. Yes. That's correct. 17 Q. Now, my question is: Is part of the reason 18 that you have that opinion that you can't make a 19 meaningful evaluation of Mr. Cowey's exposures to 20 benzene -- is part of the basis for that because of 21 Mr. Spencer's report does not give you the detail you 22 need to know whether, in fact, he's even testing a 23 product that, in fact, Mr. Cowey used? 24 A. No. 25 Q. That's not part of it? 1 A. My evaluation of Mr. Spencer -- I used 2 Mr. Spencer's report in providing an independent 3 evaluation of potential worst-case scenario for exposure 4 to Liquid Wrench given different formulations of benzene 5 in modeling that Mr. Spencer did. It's independent and 6 separate from my opinion, which is that I have no basis 7 to make a meaningful assessment of what Mr. Cowey's 8 specific exposure to benzene is. 9 Q. Can you tell the jury how much benzene 10 Mr. Cowey was exposed to when he would be underneath the 11 houses using Liquid Wrench, in what he called, I 12 believe, crawl spaces? 13 A. No, I can't. 14 Q. Does Mr. Spencer within his report provide you 15 any information regarding that particular task, what 16 Mr. Cowey was exposed to, for the Liquid Wrench he was 17 using? 18 A. Mr. Spencer uses a couple of different 19 mathematical models and assumes certain conditions with 20 respect to ventilation and air flow. I can -- I am not 21 an industrial hygienist and I can't tell you whether or 22 not those comport with conditions that would be 23 representative of a crawl space or not. 24 Q. But in Mr. Spencer's report, does he make any 25 reference to Mr. Cowey's exposures in the crawl spaces Page 81 Page 82 1 underneath the houses? Do you see that in there? 2 A. Not specifically, no. 3 Q. I want to talk to you for a minute about your 4 -- one of the major pieces of work that you said that 5 you've done over your career, is do work for 6 pharmaceutical companies. 7 A. Yes. 8 Q. Which companies? 9 A. Roche, Astra, Fujisawa, Lily, Sandoz. I'm 10 probably leaving a couple out. 11 Q. How about Bayer? 12 A. No. Not that I'm aware of. They may own 13 somebody. I mean in this business, I can't tell. 14 Q. Now, when you did work on behalf of the 15 pharmaceutical companies, would those companies actually 16 fund your work? 17 A. Well, they paid me. On occasion -- on 18 occasion I have consulted specifically in -- on issues 19 related to drug development or certification. Other 20 times I've done research on products with respect to 21 evaluating mechanisms of toxicity. I've done both, 22 sometimes interchangeably. 23 Q. Are you familiar with any asbestos-related 24 diseases? 25 A. Yes, in general. 1 Q. Have you done any reading on the disease Page 83 2 mesothelioma? 3 A. Yes. 4 Q. Do you recognize mesothelioma to be an 5 asbestos-related malignancy or cancer? 6 A. It is generally considered to be that, yes. 7 Q. Are you aware of any other known and accepted 8 causes of mesothelioma other than asbestos? 9 A. No, with the proviso that other fibers with 10 asbestos-related properties, I think, probably, have the 11 potential to do the same. 12 Q. Are you familiar with the studies that concern 13 housewives contracting mesothelioma from washing their 14 husband's clothes that contained asbestos, after work? 15 A. No, I'm not. 16 Q. Would it surprise you if there were, in fact, 17 studies of housewives contracting asbestos-related 18 malignancies such as mesothelioma from simply washing 19 out the clothes of their husbands after they had 20 returned from work? 21 MR. RILEY: Objection, form. 22 A. I would have to review those papers before I 23 could give you a meaningful opinion on then. I haven't 24 seen them and I'm not familiar with them. 25 Q. (BY MR. LUBEL) Would it surprise you, Page 84 1 Dr. Irons, that in those studies that conclude that 2 housewives exposed to asbestos while washing out their 3 spouse's clothes could contract the disease, or did, in 4 fact, contract the disease mesothelioma, that in those 5 studies there was no quantitative exposure 6 MR. RILEY: Objection, form. 7 Q. (BY MR. LUBEL) -- that was referenced in the 8 study? 9 A. Without referring -- without having a chance 10 to review the papers, I couldn't give you an informed 11 opinion on them. 12 Q. Now, one of the things that you brought with 13 you is a three-ring binder that has multiple documents 14 including studies in it, correct? 15 A. Yes. 16 Q. And I'd like to mark that as Exhibit Number 2 17 to your deposition and have either Mr. Dillard's office 18 or the court reporter make a copy of that and then 19 return the original to you, is that okay? 20 A. That's acceptable. 21 Q. Now, you were kind enough over the last break 22 we took to let me see that thick book of studies, 23 correct? 24 A. Yes. 25 Q. And if we look at, I believe, the first or Page 85 1 second study is a 1965 article about the Bradford Hill 2 -- Hill criteria that you have discussed today. Do you 3 see that? 4 A. That would probably be the first -- that's the 5 first address given by Sir Austin Bradford Hill, yeah. 6 Q. And what number is that in your book? Is that 7 the second cite -- tab, if you will? 8 A. It's Number 1. 9 Q. It's Number 1? Now, you -- you have referred 10 on many occasions to those particular scientific 11 criteria, if you will, today? 12 A. Yes. 13 Q. Is that a fair statement? 14 A. Yes. 15 Q. And one of the statements that I believe that 16 you've made is that the Sir Bradford Hill criteria 17 require quantitative exposure levels to establish or 18 make an inference of causation; is that true? 19 A. One of the criteria within the rubric of 20 Evidence Based Medicine and the Bradford Hill criteria 21 is dose response, and that is what requires quantitative 22 analysis of exposure. 23 Q. That there is, in fact, a dose response? 24 A. In order to establish that there is a dose 25 response, you have to know what the dose is, and that Page 86 1 requires quantitative analysis. 2 Q. Well, let me ask you this. Is there a dose 3 response between benzene and AML? 4 A. Yes. 5 Q. In your opinion, has that been successfully 6 plowed through, if you will, or discussed in the 7 literature? 8 A. We have a literature that provides us with a 9 quantitative dose response for benzene. 10 Q. And, in fact, dose response means, and correct 11 me if I am wrong, is that you would expect if a person 12 is exposed to more of a chemical, that the response 13 would be greater, is that generally what it means? Or 14 am I misstating that? I don't want to put words in your 15 mouth. 16 A. That requires -- in order -- in order for me 17 to answer that requires a little bit more specificity. 18 Dose response applies to populations, and it also 19 applies to individuals, but there are differences. 20 In a population dose response refers to, in 21 general, certainly given the design of most epidemiology 22 studies, the frequency of a given disease in the 23 population as a function of what they were exposed to. 24 So the number of cases or the incidence. 25 In an individual, dose response either refers Page 87 1 to the probability that they developed a certain 2 disease, or to the severity of the symptoms that they 3 may encounter if, in fact, they're related to dose. So, 4 in other words, if you increase the dose, you increase 5 the severity of the symptoms. 6 Q. And there's what's referred to as a dose 7 response curve; is that true? 8 A. That's correct. 9 Q. And if you would go ahead and draw out on your 10 yellow sheet of paper what curve you would expect to 11 see, in general, to fulfill this dose response criteria 12 of the Sir Bradford Hill criteria, or test. 13 A. I'm not exactly sure what you're asking me to 14 do. 15 Q. It was a poorly phrased question. Let me -16 let me start over on that, so that you and I are talking 17 the same language to the extent that that's even 18 possible. 19 Can I borrow your piece of paper? 20 A. Sure. 21 Q. I have drawn on the sheet of paper two axis, 22 if you will, correct? Do you see that? 23 A. Yes. 24 Q. If you would just point -- hold that up to the 25 jury so they can see what you and I are talking about. 1 All right. Now, if I can have that back, let 2 me draw another line. 3 Now, if you would take a look at that and hold 4 that up. If the -- and the line I've drawn that angles 5 upward, if your dose goes up, you would expect a greater 6 response to chemicals such as benzene; is that true? 7 A. If your -- if your dose response curve is 8 linear, which is a major assumption, then that's true. 9 Q. All right. Now, will you draw for us on a 10 separate piece of paper, or below that if you can, what 11 the dose response chart looks like for benzene? 12 A. With respect to a complete dose response going 13 from zero effect to a measurable effect, I can't do 14 that, because we don't know basically what the dose 15 response is at concentrations below which we can see an 16 effect. The observable effect is one that has to be 17 quantitated on the basis of appropriate statistics and 18 industrial hygiene. 19 Q. But would you agree, Dr. Irons, that there is 20 a dose response for benzene and MDS when you take into 21 account the Sir Bradford Hill criteria? 22 A. We have a dose response for benzene based on 23 Bradford Hill, Evidence Based Medicine, Henle-Koch. 24 There's a clear-cut dose response in the sense that 25 there are specific cumulative exposures that have been Page 88 Page 89 1 associated with a statistically significant increase in 2 acute myelogenous leukemia; and there are exposures, 3 cumulative exposures, below which we don't have any 4 evidence of a significant increase. 5 Q. But my question is: Is there a dose response 6 with respect to benzene and MDS, the disease that 7 Mr. Cowey has? 8 A. Only in the context of MDS/AML, not in the 9 context of MDS itself. 10 Q. All right. Now, can -- looking at the actual 11 1965 paper that you have before you on the Bradford Hill 12 criteria, can you locate the section for us that talks 13 about dose response? 14 A. Biological grading. 15 Q. What page? 16 A. Dose response. 17 Q. What page are you on? 18 A. 298. 19 Q. And can you read for us the relevant section 20 on the dose response criteria that you have been talking 21 about with the jury at some length today? 22 A. Well, certainly in the original Bradford Hill 23 criteria, he says, "Fifthly, if the association is one 24 which can reveal a biological gradient or dose response 25 curve, then we should look most carefully for such 1 evidence. For instance, the fact that the death rate 2 from cancer of the lung rises linearly with the number 3 of cigarettes smoked daily adds a very great deal to the 4 simpler evidence that cigarette smokers have a higher 5 death rate than nonsmokers. That comparison would be 6 weakened, though not necessarily destroyed, if it 7 depended upon, say, a much heavier death rate in light 8 smokers and a lower rate in heavier smokers. We should 9 then need to envisage some more complex relationship to 10 satisfy the cause and effect hypothesis. The clear dose 11 response curve admits of a simple explanation and 12 obviously puts the case in a clearer light." 13 Q. All right. Now, let me stop you there and 14 talk to you about that for a second. The example that's 15 given in that Sir Bradford Hill criteria document is 16 cigarette smoking, correct? 17 A. That's correct. 18 Q. And does it stand for the proposition that 19 people that smoke more are more -- or at greater risk of 20 developing lung cancer? 21 A. Yes. 22 Q. And would it also hold true, if we applied 23 that same concept to people that are exposed to benzene, 24 that people that are exposed to benzene would be at 25 greater risk if they're exposed to more benzene? Page 90 1 A. Yes. 2 Q. You don't disagree with that, do you? 3 A. No. 4 Q. And did the studies bear that out, that in 5 fact there is a relationship? 6 A. Yes. 7 Q. Now, Where in the Sir Bradford Hill criteria 8 document that you have before you does it get into the 9 quantitative issues with regard to the individual as 10 opposed to the quantitative issues regarding a 11 population? 12 A. That is the basic -- Bradford Hill does not 13 address dose response in that context. It addresses it 14 in terms of the gradient I've just described as a 15 criteria. Dose response with respect to population 16 versus individual, severity of response is subsumed in 17 the entire field of toxicology. 18 Q. Can you find for us any peer-reviewed 19 publication in your three-ring book there that stands 20 for that proposition? 21 A. Probably not. But I could cite to several 22 text books that describe it in extreme detail. I didn't 23 bring my toxicology -- basic toxicology literature with 24 me. Pharmacology toxicology, the concept of dose 25 response is extremely well exhaustively described. Page 91 Page 92 1 Q. Are any of the studies that you have with you 2 studies that address the specific product Liquid Wrench? 3 A. No. 4 Q. There is no such study, correct? 5 A. Not to my knowledge. 6 Q. Are there any studies that you brought with 7 you that addressed solvents, products that contained 8 benzene? 9 A. Yes. 10 Q. And can you just tell us the tab numbers of 11 the studies that discuss mixed solvents, if you will? 12 A. This could take a little while. 13 MR. LUBEL: Do you-all mind if we go off 14 the record while he is doing this? 15 THE VIDEOGRAPHER: Going off the record. 16 Time is approximately 12:19 p.m. 17 (A break was taken.) 1 8 T H E V I D E O G R A P H E R : We're now back on the 19 record. Time is approximately 12:25 p.m. 20 Q. (BY MR. LUBEL) You can proceed, Dr. Irons. 21 A. Yes. 22 Q. Were you able to give us the tab numbers? 23 A. There are several that deal with solvents 24 and/or benzene and solvents: 30, 31, 32, 35, 39, 40, 25 41, 42, 43, 44, 46, 47, 48; 51 is an error in that the Page 93 1 title page is correct but the chapter that was copied is 2 not the correct chapter. And for which I apologize. 3 Q. Now, would it be fair to say that the 4 remaining studies that you didn't read us off the tab 5 numbers within your three-ring binder involved pure 6 benzene? 7 A. No. There are studies in here that deal with 8 a variety of different issues, not just benzene, 9 including disease causation, specificity, and other 10 issues. There are three that deal specifically with -11 that quantitatively deal specifically with pure benzene 12 exposure. 13 Q. Within your references that you brought with 14 you, do you have the study by Hayes, Yin, and others, 15 from 2000, that was in the Journal of toxicology and 16 Environmental Health? 17 A. I don't believe so. 18 Q. The title is, "Benzene and lymphohematopoietic 19 malignancies in China." 20 A. I don't believe it's in here. 21 Q. Have you seen that study before? 22 A. Yes, definitely. 23 Q. Are you aware that that is a -- a study that 24 concludes that benzene exposures cause MDS? 25 A. It includes MDS/AML as a subcategory. It Page 94 1 includes them together as a form of AML that is -- that 2 develops secondary to exposure to alkylating agents. 3 Q. But were you aware that this particular study 4 states that benzene exposure causes MDS? 5 A. It causes -- that particular study quantitates 6 the relationship between exposure to benzene by the 7 criteria that they use, and the development of MDS/AML. 8 Q. Do you have any criticisms of this study? 9 A. Yes, I do. The -- the exposure analyses are 10 extremely sparse, and, in fact, don't actually measure 11 exposure, direct exposure, in majority of individuals, 12 which makes it very limited for use in evaluating risk, 13 quantitative risk. It does, however, reaffirm and 14 confirm some of the other findings that have been 15 described in other more reliable quantitative studies, 16 including the relationship between benzene exposure and 17 AML and AML/MDS. 18 Q. Were you aware that that particular study 19 stated that there were significant excess risks for MDS 20 from benzene exposure? 21 A. Yes. 22 Q. You don't disagree with that statement, do 23 you? 24 A. No. 25 Q. How long have you known about the study that Page 95 1 was published apparently in the year 2000? 2 A. That study is one of several that was -- that 3 basically describes the -- that paper is one of several 4 that describes the same study that was conducted by the 5 NCI in China. I have been aware of it for quite a long 6 time. 7 Q. What is the NCI in China? What do you mean by 8 that? 9 A. The National Cancer Institute. 10 Q. Is that a Chinese governmental agency? 11 A. No. It's a U.S. Governmental agency. U.S. 12 Q. Oh, the National Cancer Institute? 13 A. Yes. 14 Q. Okay. Were there Chinese scientists that were 15 involved in this study? 16 A. Yes. Yin Song Nian was the Chinese principal 17 investigator. 18 Q. Were you aware that that particular study was 19 a collaborative study that involved the Chinese Academy 20 of Preventive Medicine? 21 A. Yes. 22 Q. And as you stated, the United States National 23 Cancer -- Cancer Institute? 24 A. Yes. 25 Q. And were there, in fact, good scientists that Page 96 1 worked on this particular study? 2 A. Certainly. 3 Q. And good scientists can disagree, correct? 4 A. Yes. 5 Q. And remain good scientists? 6 A. Yes. 7 Q. You don't agree with everything that Dr. Yin 8 or Dr. Hayes have stated about benzene, I take it? 9 A. No. 10 Q. And that doesn't make them bad scientists, 11 does it? 12 A. No. 13 Q. Have you made your criticisms regarding this 14 particular study known to the National Cancer Institute, 15 and the Chinese Academy of Preventative Medicine? 16 A. Oh, yes, several times. My criticisms of that 17 study are widely known, and are consistent with some of 18 the general criticisms that have been made about that 19 study. I don't know why they even published it. 20 Q. And your criticisms about this particular 21 study, are they in writing anywhere? 22 A. I've referred -- well, I know that I certainly 23 referred to criticisms that have been made with respect 24 to the quantitative limitations of that particular 25 study, because they have been made in government 1 publications, and I've referred to them. The EPA, for 2 instance, has -- won't use that for risk assessment 3 because of the quantitative limitations in it. 4 That's widely known. I've commented on it, 5 and I think several other people have as well. 6 MR. LUBEL: Objection, nonresponsive. 7 Q. (BY MR. LUBEL) My question simply is: Have 8 your criticisms of this 2000 study by Yin and Hayes and 9 others, have you made those criticisms known to them in 10 writing? Do you have a document, a letter, another 11 article that you published that talks about these 12 criticisms? 13 A. I've referred to them before. I am certain of 14 it. Precisely where, I would have to review my writings 15 to tell you exactly. I've also publicly commented on 16 them at meetings, and I'm -- specifically one in Ottawa 17 conducted several years ago. 18 There -- they're certainly not arcane or 19 esoteric. 20 Q. Let me ask you this: There's a discussion in 21 this article that talks about how cases of MDS have been 22 reported in prior exposure to solvents, and they refer 23 to a 1990 study by -- is it Venisse? 24 A. I'd have to look at it to comment on that. I 25 -- I don't know who you're referring to. Page 97 1 Q. How about Ciccone, C I C C 0 N E? 2 A. Ciccone. 3 Q. Ciccone? 4 A. Yes. 5 Q. Have you seen that study? 6 A. Yes, I have. 7 Q. Do you have that with you? 8 A. Yes, I do. Page 98 9 Q. All right. And then they reference a case 10 control study in Great Britain by Mehlman, 1987. Do you 11 have that study with you? 12 A. No. I don't. 13 Q. Have you looked at that study? 14 A. I don't know what specific study it is. I may 15 have, may not have. 16 Q. They cite it for showing an association of MDS 17 with a history of exposure to gasoline and diesel fumes 18 or liquids. Does that spark your memory? 19 A. No. 20 Q. Have you seen the -- the Rothman work on 21 benzene? 22 A. Rothman is one of the authors on the NCI 23 series of papers that all refer to this same study. 24 Q. Have you seen his 1996 work? 25 A. There are numerous publications dealing with 1 the same study in different forms and different formats. 2 If you want to refer to a specific paper and you've got 3 it, I can give you an informed response; but, the fact 4 is there are numerous articles that have been published 5 by that group. In fact, I'm a coauthor on at least one, 6 if not more of them. So, I can't speak to a specific 7 date and know precisely which publication you're talking 8 about. 9 Q. Are you familiar with the scientist named 10 Dosemeci? 11 A. Yes. 12 Q. Is he a good doctor, good scientist? 13 A. He's a statistician. I don't know much more 14 about him than that. 15 Q. Have you seen any of his work on benzene? 16 A Yes. 17 Q. Do you have any criticisms of that work? 18 A. He's attempted to use mathematical models 19 instead of actually measuring benzene. I think in 20 general if you're going to try to develop an accurate 21 dose response, especially when you're looking at fa -22 thousands of facilities, that you have to have some 23 basis for understanding what the exposures were on a 24 quantitative basis and what the confounders are. A math 25 -- mathematical model is not a surrogate for measuring Page 99 Page 100 1 exposure. 2 Q. And I take it that you've seen the -- the work 3 out of Australia by their petroleum institute that was 4 at least sponsored in part by ExxonMobil Corporation? 5 A. If you're talking about the Health Watch 6 Study, I am generally familiar with that study. 7 Q. And were you aware that in that study, they 8 concluded that excess risk of leukemia appears to be 9 associated with lower cumulative exposures, and exposure 10 intensities when compared to other petroleum industry 11 studies where an excess of leukemia risk had been found? 12 Are you familiar with that conclusion? 13 A. I'm familiar with that, and I'm also familiar 14 with the design and issues related to that study, one of 15 which you mentioned, which is the relative inability to 16 segregate or to distinguish one type of anemia from 17 another. Excuse me, leukemia. 18 Q. So, you -- you disagree with the Australian 19 Petroleum Institute study that found that there was an 20 excess risk of leukemias even in lower exposure -- at 21 lower exposure levels than had previously been reported? 22 A. I think that that subject is some question. 23 They confirmed previous studies with respect to risks 24 associated with acute myelogenous leukemia at higher 25 concentrations, but they are -- significance is seeing Page 101 1 lower concentrations for nonspecific leukemia and they 2 have extremely few -- low numbers, so they have 3 difficulty in distinguishing between the disease types 4 and the exposures. 5 Q. Do you have any other criticisms or complaints 6 with that study other than what you've told us about? 7 A . Well, it would depend on what you're referring 8 to. That study itself, and the document that I have 9 read, is probably 200 pages long. If you're asking me 10 whether the only statement or criticism I have of it is 11 which I just said, is probably not. But, with respect 12 to the issues of exposure analysis and dose response, 13 those are my principal criticisms. It's unstable for 14 specific disease association in exposure at the lower 15 doses. 16 Q. Do you agree with the finding in that study 17 that smoking does not increase the risk of developing 18 AML? 19 A. There are other studies out -- there are a 20 number of studies, including some government studies 21 looking at meta-analysis of smokers involving huge 22 numbers of smokers, that does show an increased risk of 23 AML associated with smoking, so I would disagree with 24 the conclusion of this -- of the Health Watch study 25 insofar as it doesn't comport with much larger studies Page 102 1 that have seen an excess risk associated with smoking. 2 Q. Now, in your report in this case, you don't 3 conclude that Mr. Cowey's MDS is caused by any prior 4 smoking history he may have had, correct? 5 A. I think by and -- by and large and far away 6 the most significant risk factor associated with 7 Mr. Cowey's disease is age. That doesn't -8 Q. My question -9 A. -- exclude the possibility that smoking might 10 play a role, but I did not consider in my evaluation of 11 Mr. Cowey that smoking played a prominent role in the 12 development of his disease. 13 Q. Does your report anywhere in there state or 14 make reference to smoking playing a role in his MDS? 15 A. No. I just said I did not conclude that. 16 Q. Well, can you find for us the studies that you 17 brought with you that demonstrate that age causes MDS? 18 MR. DILLARD: Object to form. 19 A. As a risk factor, yes. Age as the -- a risk 20 factor for MDS is described several times in the 21 literature. The most recent one, I've got an excerpt 22 from a monograph by Neal Young in which he cites a 23 Birmingham study. That's one. 24 Q. (BY MR. LUBEL) But is it your opinion -25 MR. DILLARD: Why don't we get those Page 103 1 marked so we know what we're talking about? 2 A. And independently, as stated by Williamson, et 3 al, that is actually from the mid '90s showing -4 establishing the incidence of myelodysplastic syndrome 5 with age. 6 Q. (BY MR. LUBEL) My question, Dr. Irons, is, is 7 it your testimony and your opinion that age causes MDS? 8 A. Age is a co-factor. It is a confounder, a 9 risk factor. It is understanding the relationship 10 between confounders and risk factors is an important 11 tenet in Bradford Hill and Evidence Based Medicine. It 12 does not mean that one can say that age is a cause. It 13 is an important influence and co-factor that has to be 14 evaluated in determining causation, and in excluding 15 other potential etiologies. 16 Q. So, if I understand you correctly, what you're 17 saying is that as a person's age increases, or a person 18 gets older, they're at an increased risk of developing 19 MDS? 20 A. Absolutely. 21 Q. But you're not saying that age itself causes 22 MDS? 23 A. I think that's semantic. I could say the same 24 thing with respect to exposure to alkylating agents; 25 that as you're exposed to alkylating agents, your risk Page 104 1 factor increases, or your risk of developing disease 2 increases. Do the alkylating agents directly cause it? 3 That involves understanding the pathogenesis and 4 molecular mechanisms of toxicity, and to that extent I 5 can't say with respect to alkylating chemotherapeutic 6 agents or age what is the defining factor that's 7 associated with that increased risk, but it's clearly 8 established in the quantitative literature. 9 Q. Do you have any quantitative literature that 10 states, that concludes, that age causes MDS? 11 A. No. 12 Q. Is there, in fact, literature that -- that is 13 peer reviewed that states that chemotherapy agents can 14 cause MDS? 15 A. Yes. 16 Q. Peer-reviewed studies? 17 A. Yes. 18 Q. Have you brought with you all of your file 19 materials regarding your opinions and the bases for your 20 opinions today? 21 A. I believe so. Other than references you've 22 made to general textbook concepts that I haven't 23 documented in the material that I have brought with me. 24 Q. Other than that, have you brought the 25 documentation? Page 105 1 A. Yes. 2 Q. Do you have your billing records? 3 A. That I don't believe I have. 4 Q. Have you been paid for your services yet? 5 A. To date, yes. 6 Q. And do you know approximately how much you 7 have billed prior to this deposition starting? 8 A. Total fees and expenses, I believe, is on the 9 order of $10,000. 10 Q. Would that include today or just before today? 11 A. No, that's before today. 12 Q. And what is your billing arrangement? How do 13 you bill and how much? 14 A. I bill personally $500 an hour for time. 15 Q. Does that include travel time? 16 A. Yes. 17 Q. Does that include time where you're reviewing 18 materials? 19 A. Yes. 20 Q. Does that include testimony time, like here 21 today? 22 A. Yes. 23 Q. I understand that you're not going to make it 24 to this trial, if it goes forward in December, correct, 25 because you're going to be out of the country? 1 A. That's correct. Page 106 2 Q. But if you -- if this case for some reason 3 were to get continued, and you were to make it to trial, 4 do you have a different rate for attending trial? 5 A. No. 6 Q. You charge by the hourly basis for coming to 7 trial, or do you have a day rate? 8 A. Hourly basis. 9 Q. And would it be fair to say that Mr. Dillard's 10 law firm, Fulbright & Jaworski, has paid your bills up 11 through the beginning of today? 12 A. Yes. 13 Q. When did you arrive for your deposition? 14 A. Yesterday evening. 15 Q. And have you had a chance to visit with 16 Mr. Dillard or other representatives from United States 17 Steel Corporation to discuss your testimony in this 18 case? 19 A. I met with Mr. Dillard last night. 20 Q. Did you-all go to dinner? 21 A. Yes, we did. 22 Q. And did you-all visit about the case? 23 A. Yes. 24 Q. That's not uncommon between experts and the 25 lawyers that hire them, is it? Page 107 1 A. No. 2 Q. Have you been provided with the reports by 3 Dr. Nettleson and Dr. Raabe? 4 A. Yes, I have seen them. 5 Q. Did you review those? 6 A. Yes. 7 Q. And were you aware that some of the opinions 8 that they give are different than what you say? 9 MR. DILLARD: Object to the form. 10 A. In some minor degree, yes. 11 Q. (BY MR. LUBEL) In other words, were you aware 12 that Dr. Raabe has taken the position that benzene 13 exposure does not cause MDS? 14 MR. DILLARD: Object to the form. 15 A. That's -- that wasn't -- that's not exactly my 16 impression of Dr. Raabe's -- what I've read in 17 Dr. Raabe's report. I think he correctly points out 18 that there are no quantitative -- there's no 19 quantitative basis to specifically demonstrate the 20 quantitative exposure to benzene, specifically as 21 associated with the development of MDS specifically. A 22 great deal of the basis for concluding that MDS is 23 associated with benzene exposure comes from our 24 knowledge of MDS as a part of secondary AML, and the 25 enormous data base we have with respect to alkylating Page 108 1 chemotherapeutic agents and the development of that 2 disease. 3 MR. LUBEL: Objection to the 4 nonresponsive portion. 5 Q. (BY MR. LUBEL) Is it fair, Doctor, for 6 scientists such as yourself to review and rely upon 7 literature on AML in assessing MDS? 8 A. To the extent that we're talking about AML 9 that is preceded by MDS, and that is described as a 10 specific entity, yes. It's actually a di -- a specific 11 diagnostic paradigm within the WHO classification of 12 hematopoietic lymphoid diseases. 13 Q. And I take it that one of the reasons for 14 which you're able to hold the opinion that benzene 15 exposures can cause MDS is based upon the AML literature 16 that you're familiar with? 17 A. That's correct. 18 Q. All right. Let's talk for a minute about 19 latency period. And I believe that you made a statement 20 that the outside time limit -- limit for latency period 21 is 15 years? 22 A. It's certainly in terms of the quantitative 23 literature that -- that appears to be an outside number. 24 Q. Can you pull for us the peer-reviewed studies 25 that state that in order for a malignancy to be related Page 109 1 to benzene, that the malignancy must manifest itself 2 within 15 years of the last exposure? 3 A. There's no literature that's specifically 4 going to say that. The way in which latency is 5 determined is by looking at the distribution of cases 6 that -- and the time that they occur relative to 7 exposure in studies that have demonstrated a 8 quantitative relationship. 9 The only study that infers and does not 10 specifically indicate -- actually implies is the proper 11 term -- a latency as late as 15 years, would be Wong 12 update of the original pliofilm study in which the 13 follow-up cases included at least one case that appeared 14 15 years after exposure. The vast majority of cases 15 conform to the nine-and-a-half to ten-year period that I 16 referred to, and certainly prior to that study, that was 17 the general consensus and can be found in several 18 different places and documents. 19 Q. But you -- you don't have with you a 20 peer-reviewed published study that states that? 21 A. States that? No. 22 Q. Now, if we go back and we look at the Sir 23 Bradford Hill criteria, one of the criteria -- criteria, 24 I believe you referenced was temporal relationship? 25 A. Yes. Page 110 1 Q. And you've subsumed the term "latency" within 2 that criteria, correct? 3 A. Latency is in -- is included within temporal 4 relationship. 5 Q. And the temporal relationship can be important 6 because one of the things that scientists need to look 7 at is whether, in fact, there's been an exposure before 8 the disease onset? 9 A. That would be the extreme temporal -- I mean, 10 it's a spectrum. But, yes, obviously it's easier to 11 illustrate that temporal relationship than many others. 12 But if the exposure does not precede the onset of the 13 disease, you obviously have a temporal issue. 14 Q. And that's an important criteria that Sir 15 Bradford Hill surely recognized? 16 A. Yes. 17 Q. And you don't differ with that? 18 A. No. 19 Q. Let me talk to you about dose response for a 20 minute. Are you familiar with any substances for which 21 there is a dose response relationship; however, at a 22 certain point, as the dose increases, it can overwhelm 23 the system and -- and, in fact, can change the 24 mechanics, if you will, of causation? In other words, a 25 person can have a greater exposure at a certain level 1 and, in fact, have a reduced risk? Page 111 2 A. In populations, yes. For individuals, it's 3 not really biologically plausible, but for populations, 4 yes. That's well described. 5 Q. Can you give us some examples of that? 6 A. Radiation, ionizing radiation. The dose 7 response for leukemia and ionizing radiation has a bell 8 curve at the extreme end of the spectrum. 9 Q. And what is the bell curve? For people that 10 don't know, where did that -11 A. It means that at extremely higher doses, the 12 actual incidence rate goes down. That's well described 13 for agents that are extremely cytotoxic, immunogenic. 14 Q. What is the scientific explanation for the 15 bell curve? 16 A. There are two potential explanations, both of 17 which are plausible. 18 One is that in the case of radiation that the 19 radiation itself is causing other injuries that compete 20 with the incidence of the disease for survival and/or 21 sickness. The other is that they, in fact -- that 22 radiation may, in fact, influence the expression of the 23 disease in individuals as a function of damage. 24 Q. Have you seen anyone determine Mr. Cowey's 25 dermal exposures? Page 112 1 A. Specifically, no. 2 Q. Do you have an opinion as to whether or not 3 dermal exposures can contribute to hema -- hematological 4 disorders? 5 A. Unless a person is wearing respiratory 6 protective equipment, dermal exposure almost never for 7 solvent exposure represents an important factor relative 8 to inhalation. 9 Q. My point is, is can it contribute to the 10 disease process? 11 A. Yes, and studies that have basically looked at 12 quantitative benzene exposure, by definition, include 13 dermal as well as inhalation exposure. 14 Q. And have you brought those studies with you? 15 A. They -- any of the studies that looked at the 16 epidemiology of benzene, including those I have brought, 17 have as a matter of -- of fact contained within the 18 exposure scenario dermal exposure. 19 Q. How do they quantify the dermal exposure? 20 A. The dermal exposure is part and parcel of what 21 the individual is exposed to. Most of the studies are 22 quantitative only airborne exposure, but the dermal 23 exposure is part of those exposure scenarios. 24 Q. I am not disagreeing with you. I am just 25 asking you in those studies, how did they actually Page 113 1 quantify the dermal exposures? 2 A. Those studies don't. There are an independent 3 set of studies that have looked at the physical chemical 4 properties of solvent flux through the skin and 5 quantitated benzene, and other solvents specifically, 6 and those studies, as a group, confirm that solvent 7 exposure through the skin, especially for benzene, is a 8 relatively minor component, even at high levels of 9 exposure, inhalation being the dominant exposure. 10 Q. But you're not suggesting to this jury that 11 dermal exposures are safe and inhalation exposures are 12 not, are you? 13 A. I am saying that chronic exposure to benzene 14 at concentration -- or to deliver a dose of benzene via 15 the skin that would be consistent with airborne 16 exposures that are associated with adverse health 17 effects, is an extreme phenomenon, and one that's going 18 to be -- that is inconsistent with typical dermal 19 exposure even under conditions of high level inhalation 20 exposure. 21 Q. But if somebody has got -- has received both 22 inhalation exposures and dermal exposures, you're not 23 telling this jury that the dermal exposures are of zero 24 consequence? 25 A. I am saying that the major consequence, and Page 114 1 certainly the consequence associated with chronic 2 effects of benzene, is predominantly due to inhalation, 3 and that dermal exposure, to be consistent with levels 4 that we know, or doses that we know cause, for instance, 5 chronic toxicity to the blood or bone marrow, are only 6 consistent with extreme pathology to the skin and are 7 not consistent with relatively short-term or low-level 8 exposure to the skin. 9 Q. So, if I understand you correctly, in your 10 opinion, the inhalation exposures are far more important 11 than the dermal exposures to the disease process, but 12 you do acknowledge that the dermal exposures may 13 contribute to it? 14 A. Dermal exposure is going to contribute to a 15 minor extent to the overall body burden or dose of 16 benzene. The predominant exposure -- the root that I 17 believe is most consistent with chronic toxicity of the 18 blood or bone marrow is via inhalation. 19 Q. All right. Now, I want to talk to you about 20 the studies that you talked about with regard to the 21 shoes. 22 A. Yes. 23 Q. How do you refer to those? The shoe making 24 studies? 25 A. Shoe worker studies is -- Page 115 1 Q. What -2 A. -- an accurate description. 3 Q. -- benzene-containing product were they using 4 in those studies? 5 A. Benzene. 6 Q. Pure benzene? 7 A. Pure benzene used as a solvent for dissolving 8 resins, Arbetar-based resins for use as glues. 9 Q. All right. Well, some -- somewhere in your 10 testimony, I got the impression that you said that they 11 were using benzene-based resins. 12 A. It's basically -- the same thing is seen in 13 China. You take a resin which is basically an organic 14 substance derived from glue factories, like where they 15 used to take old horses, and you use benzene as the 16 solvent to resuspend and dissolve that, and that's used 17 as a glue for making shoes. It apparently is a very 18 efficient substance for gluing leather. 19 Q. What percentage of the glue contains benzene? 20 A. I'm not sure what you're asking me. 21 Q. Well, you're not saying that the glue was 100 22 percent benzene, are you? 23 A. I am saying the glue was made by taking resin 24 and dissolving it in benzene, and using it in an open 25 pot. So, the solvent was benzene. 1 Q But, how much of the glue was benzene? 2 MR. DILLARD: You're not understanding 3 him, I don't think, Lance. 4 MR. LUBEL: I'm probably not. I am not 5 trying to be -6 MR. DILLARD: I think you-all are 7 crossing paths. 8 Q. (BY MR. LUBEL) Let me start over. Were the 9 workers in these studies using glue to manufacture 10 shoes? 11 A. Yes. And they were making the glue as they 12 went by taking and dissolving resin in benzene. 13 Q. But are you saying that those studies -- they 14 state that every worker was making the glue, or were 15 there some workers that were just applying the glue, or 16 do you know? 17 A. The typical situation you're talking about 18 would be a group of people sitting around a table such 19 as this in which they are -- they have a bowl, and they 20 have resin, and they keep pouring the benzene into the 21 resin to keep it in a slurry, and they're spreading it 22 on soles and putting the shoes together. And when they 23 need to do more, they -- then, it begins to get dry, 24 they pour some more benzene in it. So it's basically -25 it's a maw-and-paw-type operation. Page 116 Page 117 1 Q. All right. And what size areas were they 2 working in? 3 A. Houses, living rooms, kitchens. 4 Q. How big were these areas? 5 A. It varies. It varies from individual -- if 6 you read -- if you read the descriptions, the anecdotal 7 descriptions, some of the situations I've seen in China, 8 they vary from very small facilities to extremely large 9 facilities. 10 Q. Facilities, you mean rooms, houses, kitchens? 11 A. Rooms, houses, kitchens, factories, workshops. 12 Q. I am talking about these houses right now. 13 Were any of the -- do you know if any of the windows 14 were open in them? 15 A. I have no idea what those conditions were 16 other than the descriptions that Aksoy provides. 17 Q. And in the study does it say whether the 18 windows were open? 19 A. There are -- they're simply descriptions about 20 the fact that these were family-run businesses, with the 21 -- basically the manufacture of shoes within the house. 22 Q. Are you familiar with the Paci study? 23 A. I am not sure what you're referring to. 24 Q. The Italian study. 25 A. Paci? Page 118 1 Q. Paci, sorry. 2 A. Yes. I am in general. 3 Q. Do you have that with you? 4 A. No, I don't. 5 Q. Were you aware that the substance being used 6 in those studies that were -- that was pure benzene? 7 A. If you've got a copy of it, I would be happy 8 to review it. I am generally familiar with it, but I 9 don't remember the specific with -- it certainly is a -10 a -- a work that discusses benzene exposure. 11 Q. We will just move on. I don't have a copy of 12 it with me. 13 Did you rule out radiation as a cause of 14 Mr. Cowey's disease? 15 A. I didn't see any basis to conclude that he had 16 exposure to radiation in the materials that I reviewed. 17 Q. Did you rule out chemotherapy agents as being 18 a cause of his M D S ? 19 A. In general, as I -- as I recall, in his 20 medical history, if you let me refer to my summary, he 21 received surgery for prostate adenocarcinoma but didn't 22 receive any radiation or chemotherapy. So I did not 23 consider that a potential cause of his disease. 24 Q. As we sit here today, it's not -- it's your 25 opinion that neither radiation nor chemotherapy induced Page 119 1 his MDS? 2 A. Yes. 3 Q. You agree with that? 4 A. Yes. 5 Q. All right. Do you agree with Dr. Youman's 6 diagnosis of MDS for Mr. Cowey? 7 A. The description that he provides is consistent 8 with the diagnosis refractory cytopenia, multilineage 9 dysplasia. 10 Q. So you agree -- you agree with him on the 11 particular cell type, too? 12 A. Based on the description, yes. I haven't 13 reviewed the slides, but the description is entirely 14 consistent. 15 Q. Now, I take it based upon what you told us 16 earlier that you disagree with Dr. Youman when he says 17 that this chromosome 8 defect is common in benzene 18 exposed workers? 19 MR. DILLARD: Object to the form. 20 A. It's certainly not consistent with the 21 secondary literature in -- specifically, and the 22 literature concerning solvent exposure in which benzene 23 is a major component. 24 Q. (BY MR. LUBEL) Have you brought with you any 25 peer-reviewed published studies that state that the Page 120 1 chromosome 8 defect that Mr. Cowey has should not happen 2 from benzene exposure? 3 A. Again, you're asking me to prove a negative. 4 What I have brought with me are peer-reviewed studies 5 that evaluate the cytogenetic abnormalities, the clonal 6 abnormalities found in individuals exposed to solvents, 7 and trisomy 8, involvement of 8, is extremely rare in 8 exposed individuals and much more frequent in the 9 control. 10 Q. Now, Mr. Dillard asked you some questions 11 about this 85 percent group -12 A. Yes. 13 Q. -- that I think you've talked about as being 14 the idiopathic group? 15 A. Yes. 16 Q. Is that correct? 17 A. Yes. 18 Q. Do you know how many people in the idiopathic 19 group, this 85 percent, that were exposed to benzene? 20 A. All of them at some level of exposure, the 21 question is how much, which is the basic question of 22 dose. 23 Q. And do you know -- do you have any reliable 24 data that provides us any meaningful information 25 regarding what those people's benzene exposure levels Page 121 1 were within this 85 percent idiopathic group, you have 2 called it? 3 A. No, neither that nor -- neither any other 4 potential cause. 5 Q. Have you understood my questions today, and 6 when you didn't, did you try to tell me? 7 A. Yes. 8 Q. Have I been courteous to you? 9 A. Yes. 10 MR. LUBEL: Thank you for your time. 11 Your turn. Need another break or are you ready? 12 MR. DILLARD: No, I'm ready. Do you have 13 any questions? Why don't you go ahead with yours? 14 EXAMINATION 15 BY MR. RILEY: 16 Q. Dr. Irons, my name is Jim Riley. I represent 17 Radiator Specialty in this case. I just want to ask you 18 a few questions, basically because of some objections 19 that were made. 20 My first question is: Dr. Levy has not given 21 his deposition in this case yet pertaining to Mr. Cowey, 22 so obviously you have not reviewed Dr. Levy's testimony 23 pertaining to Mr. Cowey in giving your deposition here 24 today, correct? 25 A. No, I have not. Page 122 1 Q. And you have -- have you spoken to Dr. Levy 2 about his opinions pertaining to Mr. Cowey? 3 A. No. 4 Q. Okay. So, basically, Mr. Dillard was asking 5 you questions about Dr. Levy's opinions, his methodology 6 and his articles, can you tell us whether or not you 7 understood that to mean his eight-page report which you 8 have reviewed? 9 A. Yes. That was my understanding. 10 Q. Now, Doctor, I want to ask you one other 11 question, or actually two, it will be. Do you have an 12 opinion that based upon the scientific literature that 13 you have referred -- that you have reviewed in the 14 course of your research, on whether the industrial uses 15 of benzene differed from the 1940s versus say the 1970s? 16 A. Yes. 17 Q. And what is that opinion, sir? 18 A. It differed dramatically. 19 Q. Dramatically in what way? 20 A. In the '40s, the accepted levels of exposure, 21 or the permissible levels of exposure to benzene were 22 huge compared to what they were in the '70s, and 23 enormous compared to what they are today. Common usage 24 was much higher. 25 MR. RILEY: That's all the questions I Page 123 1 have, sir. Thank you for your courtesy. 2 MR. DILLARD: Dr. Irons, I would like to 3 have marked as exhibits some of the articles to which 4 you have referred in your testimony, and so perhaps we 5 ought to take a quick break in order to do that, and not 6 take up the court or jury's time with it. So let's go 7 off the record for just a couple of moments if we could. 8 THE VIDEOGRAPHER: Going off the record, 9 time is approximately 1:08 p.m. 10 (A break was taken.) 11 (Exhibits 2 through 6 marked.) 12 THE VIDEOGRAPHER: We're now back on the 13 record. The time is approximately 1:16 p.m. 14 RE-EXAMINATION 15 BY MR. DILLARD: 16 Q. Dr. Irons, I'd like to have marked as exhibits 17 some of the articles to which you have made reference to 18 in the course of your testimony. Can you hand me the 19 stack? 20 A. Yes, sir. 21 Q. Thank you. I'll first show you Exhibits 3 and 22 4, and ask you what those articles -- or for what 23 proposition do those articles stand as you have cited 24 them? 25 A. Both of these articles describe the 1 age-dependent incidence of myelodysplastic syndrome in 2 the general population. 3 Q. All right. I'll next show you Exhibit Number 4 5, and ask you what -- what that is? 5 A. That is a publication of mine that deals with 6 Dideoxycytidine, which is the parent compound in the 7 experimental drug that Mr. Alley was treated with. 8 Q. Mr. Cally -- Cowey? 9 A. Cowey, I'm sorry. 10 Q. And then what is Exhibit 6, please, sir? 11 A. This is a recent publication out of the 12 University of Chicago that deals with the clinical and 13 cytogenetic associations of therapy-related 14 myelodysplastic syndrome and acute myelogenous leukemia. 15 Q. There is also a collection of articles to -16 just to your right, what -- what are those? 17 A. They're simply copies of some of -- a few of 18 the articles that are in the binder of articles that I 19 provided. 20 Q. Okay. What are their reference numbers, of Page 124 21 those articles in your binder which has been marked as 22 Exhibit Number 2? 23 A. 30, 31, 32, and 39. 24 Q. For what proposition do those articles stand? 25 A. These articles describe the relative incidence Page 125 1 of cytogenetic abnormalities in individuals developing 2 leukemia associated with solvent exposure versus those 3 who developed leukemia without any known exposure. 4 Q. Is this this 85 percent versus 15 percent that 5 was talked about earlier? 6 A. In relation to MDS, yes. 7 Q. And did they -- do these articles that you 8 have just referred to support the opinions that you 9 expressed? 10 A. Yes. 11 Q. I want to ask you about the Hayes paper 12 published in the year 2000. You're familiar with it? 13 A. Yes. 14 Q. Does the United States Environmental 15 Protection Agency use that study for evaluating the risk 16 of benzene exposure? 17 A. No. They don't. 18 Q. What has the United States Environmental 19 Protection Agency said about the value of that study in 20 evaluating the risk of benzene exposure? 21 A. Based upon the lack of direct industrial 22 hygiene and analysis of benzene exposure, in that 23 overall study, the U.S. EPA has determined that it's not 24 a reliable tool for use in quantitative risk assessment 25 of benzene. Page 126 1 Q. Was myelodysplasia, or MDS, as we've referred 2 to it here, recognized as a disease entity in the 1940s? 3 A. No. 4 Q. What benzene exposure levels were considered 5 harmful in the 1940s? 6 A. Depending upon exactly when acceptable 7 exposure levels were at 100 parts per million, and by 8 the end of the '40s, they were -- it was generally 9 accepted that they should be reduced to below 50 parts 10 per million. 11 Q. And what did the API say in the 1948 12 publication about exposure levels that were recommended? 13 A. My recollection is they recommended that 14 exposures be reduced to below 50 parts per million. 15 Q. And how was -- how would that compare to the 16 recognized exposure levels today? 17 A. The PEL in the United States today is one. 18 Q. What is PEL? 19 A. The permissible exposure limit in an 20 occupational setting. So that would be 50 times higher. 21 Q. Are you familiar with the testimony of 22 Dr. Vernon Rose on behalf of Mr. Lubel in this case? 23 A. Yes. 24 Q. Did Dr. Rose state that he was asked to 25 address an exposure assessment in this case? 1 A. I don't recall specifically what he said he 2 was asked to do. I do recall specifically that he 3 indicated he had not done so. 4 Q. I was going to ask you that. Did Dr. Rose 5 provide an exposure assessment of Mr. Cowey's alleged 6 exposure to benzene from Liquid Wrench? 7 A. My recollection is he said that he couldn't. 8 Q. Did Dr. Levy in his report provide such an 9 assessment? 10 A. No, sir. 11 Q. Based upon the literature, which you've 12 referred to as the quantitative literature that's 13 published in the reliable scientific journals, what is 14 the observed cumulative benzene level that is associated 15 with a significant excess of the disease that is called 16 AML/MDS? 17 A. Well, if you look at -- if you look at the 18 quantitative studies combined, and you look at 19 statistical significance, the lowest cumulative exposure 20 level that's been consistently demonstrated to produce a 21 significant excess is 60 ppm years, 60-per-part-million 22 years. 23 Q. Is there any scientific evidence that 24 Mr. Cowey's benzene exposure, if any, met or exceeded 25 that level? Page 127 Page 128 1 A. Not to my knowledge, no. 2 MR. DILLARD: Thank you, sir. Pass the 3 witness. 4 RE-EXAMINATION 5 BY MR. LUBEL: 6 Q. Dr. Irons, can you go ahead and pull out your 7 reference that -- I think you made a statement that the 8 EPA does not follow the 2000 Hayes and Yin study. Do 9 you have that with you? 10 A. No, I don't. 11 Q. Okay. Is there a study that says that study 12 is not of any value? 13 A. It's an official EPA publication, and it does 14 state that in performing risk assessments, quantitative 15 risk assessments associated with benzene and 16 leukemogenesis, that the Hayes study is not an 17 appropriate tool. 18 Q. Now, do you know whether this EPA, this 19 alleged EPA statement, refers to one of the older 20 studies as opposed to the 2000 version? 21 A. It refers to the study. There are numerous 22 papers relating to the study, but the original study 23 criteria and design and analysis remain the same. I 24 believe the EPA ruling was 1996. 25 Q. Okay. Were you aware that the paper that was Page 129 1 actually published in 2000 had refined information from 2 the previous work? 3 A. I couldn't speak to that. Whether or not they 4 performed any additional analyses or not, I couldn't 5 say. 6 MR. LUBEL: That's it. Thank you. 7 MR. DILLARD: Thank you, sir. 8 THE VIDEOGRAPHER: Going off the record, 9 time is approximately 1:24 p.m. 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25