Document mBymBRVN1j5OBygVqL0jmmy60

1 1 14TH JUDICIAL DISTRICT COURT 2 PARISH OF CALCASIEU 3 STATE OF LOUISIANA 4 5 STEVE LEBLANC, ET AL NO. 91-1145 6 VS. 7 CONOCO, INC., ET AL 8 9 10 11 12 13 14 15 Deposition of RICHARD D. IRONS, Ph.D., 16 taken in the above-entitled cause, pursuant to the 17 following stipulation, before Julie L. Samford, 18 Certified Shorthand Reporter, at the law offices 19 of Phelps Dunbar, 400 Poydras Street, New Orleans, 20 Louisiana, at 9:00 a.m. on the 27th day of October, 21 1992. 22 23 24 25 Associated Reporters, Inc. (504) 529-3355 2 1 APPEARANCES: 2 3 Representing the Plaintiffs: 4 HOBSON & FERGUSON BY: THEODORE M. FLERLAGE 5 2190 Harrison Avenue Beaumont, Texas 77701 6 7 Representing Defendant Moore & Companies: 8 PHELPS DUNBAR BY: BARBARA L. ARRAS 9 Texaco Center 400 Poydras Street 10 New Orleans, Louisiana 70130-3245 11 Representing Defendant Conoco, Inc., and 12 Canadian Oxy Offshore Production Company: 13 JONES, TETE, NOLEN, HANCHEY, SWIFT & SPEARS 14 BY: KENNETH R. SPEARS First Federal Building 15 1135 Lakeshore Drive P.O. Box 910 16 Lake Charles, Louisiana 70602 17 Representing Insurance Company of 18 North America: 19 GUILLORY & McCALL BY: WILLIAM T. McCALL 20 901 Lakeshore Drive, Suite 836 Lake Charles, Louisiana 70601 21 22 Representing PPG: 23 STOCKWELL, SIEVERT, VICELLIO, CLEMENTS & SHADDOCK 24 BY: BENJAMIN J. GUILBEAU, JR. One Lakeside Plaza 25 Lake Charles, Louisiana 70601 Associated Reporters, Inc. (504) 529-3355 3 1 APPEARANCES: (Continued) 2 Representing Oxy USA, Inc.: 3 E.W. HACK OXY, USA, INC. 4 SENIOR COUNSEL, LEGAL DIVISION 110 West 7th Street 5 Tulsa, Oklahoma 74119 6 Representing Conoco, Inc.: 7 SUSAN FROEHLY TEICH 8 CONOCO, INC. COUNSEL, LEGAL DEPARTMENT 9 600 North Dairy Ashford Houston, Texas 77079 10 11 12 S T I P U L A T I O N 13 14 15 It is stipulated and agreed by and among 16 counsel for the parties hereto that the deposition 17 of the aforementioned witness is hereby being taken 18 pursuant to the Louisiana Code of Civil Procedure 19 for all purposes, in accordance with law; 20 That all objections except as to the form 21 of the question and responsiveness of the answer 22 are hereby reserved until such time as this 23 deposition, or any part thereof, may be used or 24 sought to be used in evidence. 25 Associated Reporters, Inc. (504) 529-3355 4 1 EXHIBITS 2 IRONS EXHIBIT NO. 1.........................10 3 NOTICE OF DEPOSITION 4 IRONS EXHIBIT NO. 2.........................12 5 CURRICULUM VITAE 6 IRONS EXHIBIT NO. 3.........................13 7 WITNESS' CASE FILE 8 IRONS EXHIBIT NO. 3-A.......................13 9 HANDWRITTEN NOTES - LEBLANC 10 IRONS EXHIBIT NO. 3-B ......................13 11 HANDWRITTEN NOTES - STELLY 12 IRONS EXHIBIT NO. 3-C.......................13 13 MEDICAL HISTORY - STELLY 14 IRONS EXHIBIT NO. 3-D.......................13 15 WORK HISTORY - STELLY 16 IRONS EXHIBIT NO. 3-E.......................13 17 MEDICAL HISTORY - LEBLANC 18 IRONS EXHIBIT NO. 3-F.......................13 19 WORK HISTORY - LEBLANC 20 IRONS EXHIBIT NO. 3-G.......................14 21 DEPOSITION SUMMARY - LEBLANC I 22 IRONS EXHIBIT NO. 3-H.......................14 23 DEPOSITION SUMMARY LEBLANC II 24 25 Associated Reporters, Inc. (504) 529-3355 5 1 IRONS EXHIBIT NO. 3-I.......................14 DEPOSITION SUMMARY - STELLY 2 3 IRONS EXHIBIT NO. 5.........................26 ARTICLES SUPPORTING OPINION 4 5 IRONS EXHIBIT NO. 6.........................29 HOURLY BILL 6 7 IRONS EXHIBIT NO. 7.........................46 LIST OF LITIGATION TESIMONY 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 Associated Reporters, Inc. (504) 529-3355 6 1 RICHARD D. IRONS, Ph.D., 2 4200 East 9th Avenue, Denver, Colorado, after 3 being first duly sworn in the cause, testified as 4 follows: 5 EXAMINATION 6 BY MR. FLERLAGE: 7 Q. Doctor, for the record my name is Ted 8 Flerlage. I am representing the two plaintiffs who 9 are left in this case. Are you here for a 10 deposition in the Stelly and LeBlanc cases? 11 A. Yes. 12 Q. And have you prepared any materials 13 which would be a report or a summary of what your 14 findings are? 15 A. In writing, no. 16 Q. Do I take that to mean that you have an 17 oral report of some type that you have given to 18 somebody? 19 A. I have an opinion, yes. 20 Q. Has that been given to anyone in this 21 room? 22 A. Yes. 23 Q. Who is that? 24 A. Ms. Arras. 25 Q. Was that done by telephone, or this Associated Reporters, Inc. (504) 529-3355 7 1 morning, or how did you do it? 2 A. By telephone and in meeting. 3 Q. Okay. Can you tell me briefly what you 4 told her at either one of those two places? 5 MR. McCALL: Excuse me. I am going to 6 object, Ted. Again, I think you are 7 getting into an area of attorney work 8 product about what was discussed 9 between counsel and a witness, and I 10 object to that. You can ask who was 11 there, when and what, and I don't have 12 a problem with that, but the actual 13 details of the conversation I think are 14 privileged. 15 MR. FLERLAGE: I'm not asking for a 16 conversation, Counsel. I am just 17 asking for his opinion as expressed to 18 Ms. Arras at either one of the two 19 occasions, and if I limit it to that, I 20 think I am entitled to get that 21 information. That's not what I would 22 think would be either work product or 23 attorney-client privilege. 24 MR. McCALL: Just his opinions he has 25 expressed? Associated Reporters, Inc. (504) 529-3355 8 1 MR. FLERLAGE: That's all I am asking. 2 A. There is insufficient evidence to 3 suggest that multiple myeloma is associated with 4 exposure to benzene, butadiene or ethylene oxide. 5 Q. Have you gotten into the issue with 6 regard to vinyl chloride? 7 A. No, I have not. 8 Q. Are you going to express any opinion 9 with regard to vinyl chloride? 10 A. If I am asked to do so, I will, but at 11 the present time I haven't formulated an opinion. 12 Q. Okay. Now you put it in terms of 13 insufficient evidence. What do you mean by 14 "evidence"? 15 A. Data in the scientific and medical 16 literature that would support a causal 17 relationship. 18 Q. Are you limiting that to 19 epidemiological literature, or does it extend 20 beyond epidemiological literature into some other 21 scientific spectrum? 22 A. Epidemiology certainly plays a major 23 role in that process. If you have human data, 24 especially that's reliable, you should use it. 25 By the same token, experimental animal Associated Reporters, Inc. (504) 529-3355 9 1 data and mechanistic data is extremely important to 2 aid in interpreting issues that are raised through 3 epidemiology studies. 4 Q. In support of your opinion that you 5 have just expressed, are you relying on any human 6 data in particular? 7 A. Yes, the epidemiology literature that I 8 brought with me today. 9 Q. All right. And that's in the black 10 notebook that I have been pawing through here? I 11 will get to that in a minute then. With regard to 12 any other materials -- I think the first set here 13 is epidemiology; would that be correct? 14 A. The first set is epidemiology, related 15 specifically to the issue of multiple myeloma. 16 Q. And the second category? 17 A. The second category includes basically 18 some of my own work, including a book chapter in a 19 clinical toxicology text by the title of "Hazardous 20 Materials Toxicology," and I brought that because 21 that summarizes quite adequately my opinions with 22 respect to the evidence for ethylene oxide and for 23 butadiene. 24 I have brought one of my latest papers, 25 which speaks to the issue of the target cell in Associated Reporters, Inc. (504) 529-3355 10 1 certainly benzene bone marrow toxicity. I brought 2 just a couple of papers that deal with the issue of 3 the ontogeny of multiple myeloma and its origin. 4 Q. And that would be the next category? 5 A. Yes. 6 Q. And I have brought, by no means not 7 all, but I brought some of the papers, including my 8 own, which support my opinions with respect to 9 butadiene and ethylene oxide. 10 Q. And that's in the final category that 11 you have got in the loose-leaf binder? 12 A. Yes. 13 Q. Okay. Have you been asked to look into 14 any cause and effect relationship of vinyl chloride 15 and multiple myeloma? 16 A. No. 17 Q. Okay. So at this point, anyway, you 18 don't intend to go any further and look into that? 19 A. Not unless I am asked to do so. 20 (EXHIBIT NO. 1 WAS MARKED) 21 BY MR. FLERLAGE: 22 Q. Okay. All right, Doctor. It's a 23 little bit late for this, but anyway I've got 24 Irons Exhibit No. 1 as the notice of deposition. 25 Have you seen that? Associated Reporters, Inc. (504) 529-3355 11 1 A. Yes. 2 Q. In addition to the materials you have 3 just described in your notebook, what other 4 materials did you bring which would be responsive 5 to the notice of deposition? 6 A. I brought the materials I have received 7 from Ms. Arras, including a letter that accompanied 8 medical records that I received and some summaries 9 that I received from her. I am missing one letter 10 that I have misplaced. 11 Q. That's probably a smoking gun, I guess, 12 right? 13 A. I know what the substance was. It 14 notified me that Fautheree was being eliminated 15 from the suit. 16 Q. So with the exception of that letter 17 then, this would be the correspondence that you 18 received? 19 A. Yes, plus the medical records, which I 20 have not brought with me. 21 Q. Now the medical records you received 22 would be the eight-inch thing that we described 23 yesterday? 24 A. Yes. 25 Q. And you have got a summary also of Associated Reporters, Inc. (504) 529-3355 12 1 that? 2 A. That's in there. 3 Q. Have you summarized the records 4 independent of counsel? 5 A. Yes, to a very minimal extent, just so 6 that I keep track of time and place. 7 Q. So you have got two sheets of 8 handwritten notes here, which would be one on 9 LeBlanc and one on Stelly? 10 A. Yes. 11 Q. And this is in your handwriting? 12 A. Yes. 13 Q. The LeBlanc, and Stelly is also? 14 A. Yes. 15 Q. Is this a current copy of your CV? 16 A. Yes. 17 Q. And that would be up-to-date as far as 18 publication is concerned? 19 A. To the day. 20 Q. Okay. 21 A. I can't do better than that. 22 Q. No. 23 (EXHIBIT NO. 2 WAS MARKED) 24 BY MR. FLERLAGE: 25 Q. I have had that marked for the record Associated Reporters, Inc. (504) 529-3355 13 1 as Exhibit No. 2, and that will be the CV. 2 Exhibit No. 3 I will mark as the folder 3 that the materials that we have just gone through 4 came in, and then we can go through this and mark 5 them with letters and suffixes if it's okay. 6 3-A and 3-B would be the pages of 7 handwritten notes from the doctor, one on LeBlanc 8 and one on Stelly. 9 The next items will be as described by 10 the doctor, the medical records summary and the 11 work history of Maurice Stelly, Jr., which will be 12 C and D, and the medical records summary and the 13 work history summary of Steve LeBlanc, E and F. 14 (EXHIBIT NOS. 3-A THROUGH 3-F WERE MARKED) 15 MR. McCALL: Which one goes first, Ted? 16 The medical summary first? 17 MR. FLERLAGE: The medical summary 18 first, yeah. 19 BY MR. FLERLAGE: 20 Q. And then you have some deposition 21 summaries in here, I take it, which were supplied 22 by counsel. 23 A. Yes. 24 Q. And the summaries are Volumes I and II 25 of the LeBlanc deposition? Associated Reporters, Inc. (504) 529-3355 14 1 A. Yes. 2 Q. And then the Stelly deposition? 3 A. Yes. 4 Q. Okay. Have you received any other 5 deposition summaries or depositions in this case? 6 A. I have seen Volumes I and II of the 7 LeBlanc deposition. I have seen the Stelly 8 deposition. I have no other summaries that I am 9 aware of. 10 Q. Have you reviewed any other depositions 11 with regard to this case, whether from a fact 12 witness or an expert witness? 13 A. No. 14 MR. FLERLAGE: Okay. Why don't we just 15 mark these G, H, and I. 16 (EXHIBIT NOS. 3-G, 3-H, AND 3-I WERE MARKED) 17 BY MR. FLERLAGE: 18 Q. Except for the one piece of 19 correspondence that I haven't had numbered, is that 20 the sum and substance of your file in the case? 21 A. Yes, with respect to what I have 22 received. 23 Q. Yes. Thank you. And have you done any 24 other research or acquired any other materials with 25 regard to this case? Associated Reporters, Inc. (504) 529-3355 15 1 A. Well, in response to the deposition 2 notice, I brought with me all other materials that 3 I have written that deal with the case. This is 4 just some notes I took on my first phone call with 5 Ms. Arras. 6 Q. And at the top is written "Radiation, 7 Farming-Livestock" and ""Coal Tar-Asphalt." 8 A. Yes. 9 Q. Would they be potential exposures 10 involved in the case? 11 A. When she mentioned multiple myeloma, 12 those were my first thoughts with respect to 13 occupations or exposures, that there is literature 14 to suggest a causal relationship. 15 Q. Okay. And this was initially, without 16 doing any specific research in the case or knowing 17 anything about specific exposures; is that right? 18 A. That's right. 19 Q. So this would be very early on in the 20 case when you first contacted Ms. Arras? 21 A. When she contacted me, yes. 22 (EXHIBIT NO. 3-J WAS MARKED) 23 Q. Doctor, I have been referring to the 24 Richard Irons deposition which was dated or done 25 December 17th, 1991, just as a framework for Associated Reporters, Inc. (504) 529-3355 16 1 background information and what have you, and that 2 was in the case of Ellis versus a number of 3 defendants. Do you remember taking that deposition 4 or giving that deposition? 5 A. Yes. 6 Q. That was December. Since that time, 7 without going into the CV, have your qualifications 8 or educational background or any of those things 9 changed in any degree? 10 A. No. 11 Q. With regard to what you are doing on a 12 day-to-day basis with your occupation, has that 13 changed in any sense since December? 14 A. No. 15 Q. Do you have the same grants and the 16 same contracts that you described at that time that 17 you are still working on, on an ongoing basis? 18 A. Yes. The same ones that I have, I had 19 then; vice versa, the same ones I had pending then, 20 I have pending now. 21 Q. Have you sought any other grants from 22 either the government or any other independent 23 agency for research? 24 A. Yes. 25 Q. What areas would they be in? Associated Reporters, Inc. (504) 529-3355 17 1 A. Biomonitoring for cancer, the National 2 Cancer Institute, would be the one that I currently 3 have in preparation right now, and I expect over 4 the course of the next year I will probably propose 5 and submit one or two additional grants. 6 Q. Would they be in areas which are 7 germane to the issues of this case? 8 A. Yes. 9 Q. And in what way? 10 A. Virtually all my research is focused on 11 mechanisms of bone marrow toxicity and 12 leukemogenesis, either in animals or man, and 13 understanding those mechanisms, so anything that I 14 am likely to submit as a research proposal is going 15 to have some bearing on it. 16 Q. To whom have you submitted the 17 proposals? 18 A. I am in the process of tendering a 19 submission to the National Cancer Institute. I 20 have not yet submitted it, but will by the middle 21 of next month. 22 Q. Have you submitted any further 23 proposals than those described in the December 24 deposition to either the API or CMA? 25 A. I don't believe so. Associated Reporters, Inc. (504) 529-3355 18 1 Q. All right. Do you still have ongoing 2 research on behalf of API and CMA? 3 A. Yes. 4 Q. Same projects you discussed then? 5 A. Yes. 6 Q. Have you addressed any meetings of 7 membership of the API or CMA since that time? 8 A. Memberships meetings? I attended a 9 workshop that involved EPA, API, representatives of 10 various regulatory agencies in Warrenton, Virginia, 11 last month. 12 Q. What was the substance of that meeting? 13 A. State of the art of the science as it 14 forms a biological basis for evaluating risk 15 assessment. 16 Q. That would be the present state of the 17 art? 18 A. Yes. 19 Q. Who else gave a presentation or spoke 20 at that meeting? 21 A. Bernie Goldstein from Rutgers, several 22 people from the Environmental Protection Agency, 23 Canadian Environmental -- it's not the 24 Environmental Protection Agency, but Canadian 25 Health and Welfare, Canada, Robert Snyder from Associated Reporters, Inc. (504) 529-3355 19 1 Rutgers, Michelle Midensky from C.I.I.T., Raymond 2 Tyce from Research Triangle Park, a variety of 3 different researchers and regulators who were 4 interested in benzene toxicity. 5 Q. Was there a report generated or a 6 publication generated from that meeting? 7 A. No. It was a very informal discussion. 8 Q. Was there a consensus reached among the 9 people who gave presentations, to the best of your 10 knowledge? 11 A. In a way, yes, and that is that the 12 only answer that is going to improve the process of 13 risk assessment for benzene is going to be 14 mechanistic biologic studies that provide a clear 15 understanding of the mechanism in action. 16 Q. Which would be the pathogenesis 17 essentially of how the metabolites affect the cell 18 structure? 19 A. That would be a fair description. 20 Q. Would that also be true of the other 21 chemicals we are talking about, butadiene and/or 22 ethylene oxide? 23 A. You are asking someone who -24 Q. I'm sorry. Let me strike that. You 25 didn't discuss any of the other chemicals at this Associated Reporters, Inc. (504) 529-3355 20 1 particular meeting? 2 A. No. 3 Q. Let me get to that later then. Was 4 this the only presentation or meeting of any type 5 that you had with organizations such as this, CMA, 6 API? 7 A. I probably have given a progress report 8 to -- yes, I gave a progress report to CMA on my 9 butadiene research at roughly the same time. 10 Q. So you have a reasonably new butadiene 11 paper here? 12 A. I have a butadiene paper in submission. 13 It's not yet in press, so it's not in this folder. 14 Q. What is the gist of that paper? 15 A. It characterizes the cytocon 16 specificity of the cell populations that are 17 sensitive to the monoepoxy epoxibutene, which is 18 the monoepoxy metabolite of butadiene. 19 Q. Is there an English translation for 20 what you just said? 21 A. We are looking at the alterations that 22 the metabolites of butadiene cause on bone marrow 23 cells in culture. 24 Q. Would that be similar to the research 25 that has already been done for benzene, for Associated Reporters, Inc. (504) 529-3355 21 1 instance? 2 A. Yes. 3 Q. You have already gone that route with 4 benzene, I take it, and you have opinions with 5 regard to how benzene affects -- the metabolites of 6 benzene, at least, affect the marrow; is that 7 correct? 8 A. Yes. 9 Q. So you are doing the same type of 10 studies with regard to butadiene? 11 A. Yes. 12 Q. Do you have any conclusions with regard 13 to the effects of butadiene? And again, I am 14 limiting that to the bone marrow. 15 A. To the extent that we have examined it, 16 which is the mouse, I think that it's fair to say 17 that butadiene does not behave in a manner that's 18 similar to benzene. 19 Q. Okay. In what ways would it be 20 different or characterized as different? 21 A. It does different things to different 22 cells. That pretty well summarizes it. 23 Q. Different stem cells, or different 24 types of groups of cells or classifications of 25 cells? Associated Reporters, Inc. (504) 529-3355 22 1 A. Well, it depends how you define "stem 2 cell." Different cells that are at different 3 stages of differentiation. 4 Q. Would it be fair to say then that, at 5 least in your opinion, with regard to the present 6 status of your research into butadiene, that it 7 does not do the same things to the same cells that 8 the benzene would do? 9 A. Yes. 10 Q. Okay. That is sort of a summation of 11 the whole? 12 A. Yes, in the mouse. 13 Q. In the mouse? Can you translate those 14 experiments into the human experience? 15 A. We are beginning to do that now. We 16 are actively involved in directly comparing the two 17 species, but we have no data on which to make any 18 statements of the similarities or differences at 19 this point. 20 Q. Have you been able to get marrow 21 specimens, human marrow specimens, to use for your 22 research? 23 A. Yes. 24 Q. You talked about some sources that you 25 had back in December. Have those changed at all Associated Reporters, Inc. (504) 529-3355 23 1 for marrow? 2 A. Yes. 3 Q. In what way? 4 A. I am buying marrow now from human 5 volunteers. 6 Q. So you're harvesting marrow from people 7 in the same sense that hospitals do for -8 A. Yes. 9 Q. Okay. Are there any specific marrow 10 and/or blood types that you are after when you are 11 harvesting? 12 A. I don't understand the question. 13 Q. Is there a type of human blood type or 14 human marrow component which would be more 15 susceptible in your opinion to any of these 16 processes? 17 A. You mean a particular individual? 18 Q. Yes. 19 A. No. No, at this point we are looking 20 at normal individuals and we are looking at normal 21 bone marrow. We are not distinguishing or 22 selecting marrow on any basis I can think of, 23 except that they be AIDS-free, that women not be 24 pregnant, and we are keeping information such as 25 smoking history, that type of thing. Associated Reporters, Inc. (504) 529-3355 24 1 Q. When you do the harvest, do you do it 2 from the iliac crest or do you do it from the 3 sternum? How do you do it? 4 A. I don't know anybody that does sternum 5 anymore. 6 Q. Okay. 7 A. Iliac crest. 8 Q. What quantity do you receive from the 9 donors? 10 A. It varies, but normally 5 ML's. 11 Q. You have some papers, I believe, that 12 you brought with you on ethylene oxide also. 13 A. Yes. 14 Q. And is there any ongoing research which 15 would be similar to what you have just described in 16 the butadiene concept for ethylene oxide? 17 A. Not to my knowledge; certainly not in 18 my laboratory. 19 Q. What would be your opinion of the 20 capability of ethylene oxide to cause bone marrow 21 changes as a result of exposure to ethylene oxide? 22 A. The answer to that question depends on 23 a lot of variables. If you are talking about an 24 in vitro culture system where you introduce 25 ethylene oxide into the culture directly, very much Associated Reporters, Inc. (504) 529-3355 25 1 like we are with metabolites, benzene or butadiene, 2 I would surely expect to see some toxicity, because 3 ethylene oxide is a direct-acting, very reactive 4 molecule. In vivo, I know of no -- I have no basis 5 on which to give you an informed answer to that. 6 Q. Either animal or otherwise? 7 A. No. It's clearly reactive. It will 8 cause toxicity directly to cells in the blood. I 9 think that's fairly well established, so the issue 10 of whether or not ethylene oxide in high 11 concentrations can be toxic I don't think is 12 controversial; it's a question of what its 13 potential for causing leukemia or lymphoma is, and 14 those are totally different subjects. 15 Q. Would your opinion that ethylene oxide 16 does not cause or did not in this case cause the 17 multiple myelomas that these gentlemen purportedly 18 have be based on the epidemiology with regard to 19 ethylene oxide? 20 A. Yes. 21 Q. The documents that you have brought 22 with you, I take it they are the only copies that 23 are here at present. 24 A. Yes. 25 Q. Do you mind leaving those with the Associated Reporters, Inc. (504) 529-3355 26 1 court reporter? 2 A. If I can get these copied and returned 3 to me, that would be fine. 4 MR. McCALL: We can do that. We can 5 have them photocopied and ship them 6 back to you; is that okay? 7 THE WITNESS: Yeah. 8 BY MR. FLERLAGE: 9 Q. Since you have described the 10 categories, and we may be referring to the 11 individual articles at some time during the 12 deposition, if that happens I will have them 13 individually marked, but for purposes of 14 record-keeping, I will call it Exhibit 5 for the 15 whole package. 16 (EXHIBIT NO. 5 WAS MARKED) 17 BY MR. FLERLAGE: 18 Q. Doctor, do you understand this to be a 19 discovery deposition? 20 A. Yes. 21 Q. And are you scheduled to appear at the 22 trial of the case? 23 A. It is my understanding that if this 24 case goes to trial, I will testify. 25 Q. Do you know when the trial date is? Associated Reporters, Inc. (504) 529-3355 27 1 A. No. 2 Q. If I told you November 16th as a 3 startup time or potential startup time, would you 4 have anything in your schedule which would 5 interfere with your testimony sometime thereafter? 6 A. Teaching. It's a matter of scheduling 7 in between my lecturing and teaching 8 responsibilities. 9 Q. You believe you could make sufficient 10 time to get to Lake Charles? 11 A. Yes. 12 Q. And the testimony and then to leave, 13 would that take approximately three days out of 14 your schedule? 15 A. Two or three, depending upon how it 16 goes, connections and that type of thing. 17 Q. Now you testified that you were 18 retained in these cases by Ms. Arras? 19 A. Yes. 20 Q. And are you also, to the best of your 21 knowledge, working on behalf of the other 22 defendants in the case? 23 A. To the best of my knowledge, yes. 24 Q. So the testimony you give today will be 25 on behalf of any defendants remaining? Associated Reporters, Inc. (504) 529-3355 28 1 A. I assume so. My testimony is my 2 testimony irrespective of who's here. 3 Q. For purposes of litigation such as 4 this, do you have a particular billing rate? 5 A. I have a standard billing rate that I 6 use for all consulting activities, whether it's 7 litigation, consultation to various industries or 8 agencies, and that's 300 an hour. The only 9 exception is when I provide an advisory role to 10 regulatory agencies or the U.S. government, I go by 11 whatever the standard daily rate is. 12 Q. Do you have any invoices for work 13 performed to this point in these two cases? 14 A. No. 15 Q. Can you estimate how many hours you 16 have applied to the LeBlanc and Stelly evaluations? 17 A. Yes. I wrote this down. I brought 18 this in response to the deposition notice. This is 19 a record of my hours to date. 20 Q. Okay. Now this is LeBlanc, et al, and 21 it has dates over on the left hand, next to the 22 margin, and then these are hours on this side? 23 A. Yes. 24 Q. And each of these hours would have been 25 at the rate of $300 per hour? Associated Reporters, Inc. (504) 529-3355 29 1 A. Yes. 2 Q. There is no total at the bottom here. 3 May I have this marked as Exhibit 6? 4 A. That, I would like back. 5 (EXHIBIT NO. 6 WAS MARKED) 6 BY MR. FLERLAGE: 7 Q. This comes up to 10-26, which is 8 travel, and that would be to get here? 9 A. Yes. 10 Q. And then 10-25 would be copying 11 articles and record review? 12 A. Yes. 13 Q. That would be these articles? 14 A. Yes. 15 Q. For courtroom appearances and 16 depositions, do you bill at the same rate? 17 A. Yes. 18 Q. So you consider that consultation also? 19 A. Yes. 20 Q. You indicated that you do consultation 21 to industry. 22 A. Yes. 23 Q. Would that be petroleum and chemical 24 industries? 25 A. To some extent, yes; predominantly Associated Reporters, Inc. (504) 529-3355 30 1 pharmaceutical industry. 2 Q. Are you doing any current consulting 3 work with any of the individual petroleum or 4 chemical companies? 5 A. Not to my knowledge. 6 Q. Okay. How many people work with you? 7 A. In my laboratory? 8 Q. In your lab, yes. 9 A. Seven to ten. 10 Q. Is anyone else in your laboratory 11 actively seeking grants or research? 12 A. No. 13 Q. So everything would come in through 14 you? 15 A. Yes. 16 Q. If you could estimate for me, what 17 percentage of your professional time is devoted to 18 litigation matters? 19 A. It's less than 10 percent. It's 20 roughly between say 7 and 10 percent. 21 Q. If I asked you the same question, what 22 percentage of your gross income would be derived 23 from litigation matters, would it be in the same 24 range? 25 A. No. If I look at consulting as a Associated Reporters, Inc. (504) 529-3355 31 1 whole, it's roughly half of my income, maybe 2 slightly more. 3 Q. That would be litigation-based 4 consulting work? 5 A. It would be litigation. It would also 6 be pharmaceutical. It would be everything that I 7 do that involves compensation. Advice to 8 regulatory agencies, virtually all my consulting 9 activities. 10 Q. What I was trying to do, though, is 11 break out from that the litigation. Can you do 12 that right now? 13 A. Between 60 and 70 percent, probably. 14 Q. Of that would be litigation? 15 A. Yes. 16 Q. So 60 to 70 percent of the 50 percent 17 would be the litigation-based consulting work, as 18 you are calling it? 19 A. Yes. 20 Q. And that would be on an income basis, 21 gross income? 22 A. Yes. These are rough figures, believe 23 me. 24 Q. Can you characterize the amount of 25 weight you would place in epidemiology as opposed Associated Reporters, Inc. (504) 529-3355 32 1 to, as you are calling it, mechanistic type 2 studies, with regard to forming an opinion in this 3 case? 4 A. That answer depends on a number of 5 factors. As I mentioned before, if you have human 6 data, I think you should use it. 7 But by the same token, epidemiology 8 studies are extremely hard to control. They are 9 extremely hard to use in a manner that gives you a 10 definitive answer to your question. It's not like 11 a hypothesis-driven exercise in the laboratory, 12 where you can control all of the parameters that go 13 into it. So epidemiology is a lot more difficult 14 as a tool, but again, it deals with humans. 15 I tend to view epidemiology studies in 16 an area as a whole, as opposed to taking individual 17 studies and arriving at an opinion based upon a 18 single study, and that's because I don't find very 19 many epidemiology studies to be definitive. You 20 have to look for a pattern. 21 On the other hand, it is possible, if 22 well done, to obtain definitive answers with 23 experimental studies, but they tend to have a much 24 narrower scope and they are much more focused. 25 Q. By experimental studies, do you mean Associated Reporters, Inc. (504) 529-3355 33 1 something like an animal study or a -2 A. Either an animal study or a study using 3 tissues from either animals or humans. 4 Q. Which is what you are engaged in with 5 the bone marrow and what have you? 6 A. Yes. 7 Q. By "narrower," you mean focused in on a 8 specific cell or a specific area of the body as 9 opposed to a more sweeping conclusion of occurrence 10 of disease? 11 A. Yes. I think that these types of 12 studies are very valuable as tools with which to 13 test the validity of assumptions that are raised in 14 epidemiology studies. 15 Q. Is there any particular epidemiology 16 that you are relying on in support of your opinions 17 with regard, first of all, to benzene and the 18 occurrence of Mr. Stelly and Mr. LeBlanc's 19 diseases? 20 A. Yes, and I have brought copies of those 21 studies with me. 22 Q. Okay. So the list of epidemiology that 23 we have in Section 1 of Exhibit 5, I think it is, 24 the Tabershaw report from '74, the Rinsky studies, 25 '81, '87, some of Dr. Wong's materials are in Associated Reporters, Inc. (504) 529-3355 34 1 there. Is there anything else that you would point 2 to in the realm of epidemiology that you are 3 relying on? 4 A. Rushton and Alderson. 5 Q. Would that be the '83? 6 A. Yes. And when you say "rely on" I 7 would like to qualify that. 8 Q. Sure. 9 A. I don't rely on any individual article 10 totally. I evaluate it for what I consider are its 11 strengths and weaknesses and I arrive at an 12 opinion, but that does not mean that, in the sense 13 of relying on everything in an article or a report 14 as being accurate or that I agree with, I don't 15 rely on individual papers in that manner. 16 Q. Do you perform your own what I will 17 call meta-analysis when you look at the sum total 18 of the epidemiology in the area? 19 A. Meta-analysis has gotten to be a 20 buzzword. To the extent that it allows one to take 21 a number of different studies and evaluate them as 22 a group, it is a valuable tool. 23 But by the same token, I don't think 24 that it requires a meta-analysis to see the 25 obvious; therefore, if you have consistency within Associated Reporters, Inc. (504) 529-3355 35 1 a series of epidemiology studies, each of which 2 brings to the arena their own strengths and 3 weaknesses, I don't think you necessarily -- from 4 my own point of view, I don't need a meta-analysis 5 to reach an opinion. 6 Where I think a meta-analysis is useful 7 is where you can't do that, but that has not been 8 my problem in this particular case. 9 Q. Consistency being report to report to 10 report? 11 A. Yes. As I said before, an individual 12 epidemiology study to me is rarely definitive. You 13 really have to look at the sum total of literature 14 that's there in arriving at an opinion, and you 15 look for a pattern, whether there is a consistent 16 pattern. 17 One problem associated with controlling 18 epidemiology studies, especially if you are dealing 19 with a broad segment of the population, is 20 ascertaining what's a negative result, and whether 21 or not there is a causal association between an 22 alleged exposure or a hypothesized exposure or 23 occupation and a given finding. 24 If in fact there is such a 25 relationship, one should expect to see it Associated Reporters, Inc. (504) 529-3355 36 1 repeatedly and see it over and over again, and you 2 see a pattern established across a variety of 3 studies with different populations. 4 Q. With regard specifically now to 5 multiple myeloma, can you characterize the, for 6 lack of a better word, rareness of that disease 7 process in the general spectrum of the population? 8 A. Yes. It is by no means an esoteric or 9 rare tumor type. It occurs approximately, and this 10 will vary depending upon who you read and what 11 study you look at, but my best recollection is the 12 last figures that I have seen, it accounts for 13 approximately 1 percent of human cancers. And it 14 probably represents somewhere between 10 and 20 -15 probably not 20, it's probably 10 to 15 percent of 16 hematopoietic and lymphoid neoplasms. 17 Q. Generally, the other diseases that 18 would fall into that category would be what? 19 A. Leukemias, hematopoietic lymphomas. 20 That would be it. 21 Q. So it would be you said 10 to -22 A. I would say it's going to be somewhere 23 between 10 and 15 percent. 24 Q. Of all those diseases? 25 A. Yes. It's definitely an age-related Associated Reporters, Inc. (504) 529-3355 37 1 disease, which makes it somewhat difficult to 2 evaluate incidence in certain cases. 3 Q. That was the next area of questioning. 4 I was wondering how, in an epidemiological sense, 5 you can get the degree of consistency in findings 6 that you need to form a conclusion that the 7 epidemiology is proven as to causation with a rare 8 disease. 9 MS. ARRAS: I am going to object to the 10 form. He has just testified that it's 11 not rare. 12 MR. SPEARS: That's correct. 13 BY MR. FLERLAGE: 14 Q. Let me try again. Is there enough 15 multiple myeloma to form an opinion based on 16 epidemiology alone as to causation? 17 MS. ARRAS: I am going to object to the 18 form. Are you asking just generally? 19 MR. FLERLAGE: Yeah. 20 MS. ARRAS: In a hypothetical, not 21 specific to any disease process? 22 MR. FLERLAGE: Yes. 23 A. Could you repeat the question, please? 24 Q. Is there enough incidence of multiple 25 myeloma in the population as a whole to form Associated Reporters, Inc. (504) 529-3355 38 1 conclusions based on epidemiology as to any 2 causation? 3 A. If you were to ask me that question in 4 the mid '80s, I would have said no. Having 5 reviewed the literature again at Ms. Arras' request 6 in preparation for this case, I am satisfied that 7 there is a sufficient literature base to reach that 8 conclusion. 9 Q. And that's based on your current review 10 in these two cases? 11 A. Yes. 12 Q. Had you performed such a review prior 13 to your testimony in the Ellis case? 14 A. No. As I said, the last time I visited 15 the issue of multiple myeloma was in the mid '80s, 16 and I haven't taken a serious intensive look at 17 that literature prior to preparation for this case. 18 Q. Well, limiting this question to one of 19 those esoteric diseases, whatever it may be, very 20 rare, extremely rare in incidence, is epidemiology 21 a useful tool in determining cause and effect in 22 the context of such a disease? 23 A. Actually, it is. That's because if a 24 disease is so rare that you see extremely few cases 25 in the general population, then when you begin to Associated Reporters, Inc. (504) 529-3355 39 1 see cases occurring, your attention is immediately 2 drawn to the fact that there may in fact be a 3 common etiology. So rarity is not always a 4 handicap. It can in fact provide a useful 5 indicator. 6 Q. Is the concept of confidence intervals, 7 the 95 percent and the range of the interval, does 8 that increase with the degree of rarity of the 9 disease? 10 A. It's going to depend on the power of 11 your study. I mean it's not just the incidence of 12 the disease. It also depends upon your study 13 group, how it's designed and what the questions are 14 that you are asking. You have to look at both 15 sides of the equation to determine what goes into 16 determining the probability of a finding or seeing 17 a difference between two compared populations. 18 Q. Doctor, at what point in time did 19 epidemiology become a useful tool in determining 20 cause and effect as a science? Can you answer 21 that? 22 A. I am not sure I understand the 23 question. If you are talking about the very first 24 occupational disease that was ever recognized as 25 such, most texts refer back to scrotal cancer in Associated Reporters, Inc. (504) 529-3355 40 1 chimneysweeps in England. It's standard academic 2 fare for introducing the topic of epidemiology. 3 Q. And that would have been how long ago? 4 A. We are talking about 100, 150 years. 5 Q. Doctor, have you discussed either your 6 research or your opinions in this particular case 7 with any other individuals, any other experts, I 8 should say? 9 A. I have had a brief conversation with 10 Dr. Wong and Dr. Bickers in this case. 11 Q. When did you talk to Dr. Wong? 12 A. I believe it was last week. 13 Q. It was prior to his testimony? He 14 testified yesterday in deposition. 15 A. Yes. 16 Q. And Dr. Bickers, when did you speak 17 with him? 18 A. Same time. 19 Q. Did you have a conference call type 20 arrangement? 21 A. I believe so, as I recall. 22 Q. Was it in conjunction with any 23 attorneys? 24 A. Yes, Ms. Arras. 25 Q. Ms. Arras? Okay. At that time, Associated Reporters, Inc. (504) 529-3355 41 1 generally, did you discuss each others' opinions? 2 MS. ARRAS: I am going to object. We 3 have established the fact that there 4 was a conversation, and I think if we 5 get into any of the substance of it, we 6 are treading very close to work 7 product. You are going to have an 8 opportunity to question Dr. Bickers. I 9 don't know if you are the person taking 10 the deposition, but his deposition is 11 scheduled for Friday. You can obtain 12 his opinions at that time. You have 13 Dr. Irons' and Dr. Wong's. 14 BY MR. FLERLAGE: 15 Q. Are you basing any of your conclusions 16 or opinions in this case on any conversations you 17 may have had with any other expert? 18 A. No. 19 Q. So whenever this conference call 20 occurred, a week or a week and a half ago, whenever 21 it was, your opinions today are not based on 22 anything that was derived from that? 23 A. Let me clarify that. I have obtained 24 one or two pieces of information with respect to 25 Dr. Wong's own studies that have been useful to me, Associated Reporters, Inc. (504) 529-3355 42 1 but I wouldn't say that they played a substantive 2 role in my reaching my opinion. 3 Q. Can you categorize the bits of 4 information you received from Dr. Wong? 5 A. Yeah. I asked him for clarification as 6 to some of the data that he presented in one of his 7 papers. 8 Q. And is that paper in your Exhibit No. 5 9 materials? 10 A. Yes. 11 Q. And which one was that? 12 A. The 1986 petroleum refinery study. 13 Q. Okay. And what information did you ask 14 him? 15 A. I asked him for a breakdown of what 16 multiple myeloma incidence was relative to other 17 lymphoid neoplasms, and he told me. 18 Q. Have you discussed the cases, meaning 19 Stelly and LeBlanc, with any other consulting or 20 non-consulting experts? 21 A. No. 22 Q. Since December, I guess -- I think you 23 talked about this briefly. Since December, have 24 you been deposed in any other litigation matters? 25 A. Yes, two. Associated Reporters, Inc. (504) 529-3355 43 1 Q. And do you remember the case names? 2 A. Albertson versus KNE Energy in June, 3 and Conde versus Velsecal in August. 4 Q. Were they chemical cases? 5 A. Yes. 6 Q. What types of substances were involved? 7 A. The allegation in Albertson is benzene. 8 Q. Is it a leukemia case? 9 A. No. I don't know what kind of a case 10 it is. I am still trying to find out what the 11 diseases are. 12 Q. And this is after your deposition? 13 A. That's right. 14 Q. How about the other case? 15 A. There are no leukemias in the Albertson 16 case, I can tell you. Conde versus Velsecal is 17 chlordane, and it's a variety of allegations 18 related to health effects, none of which are 19 leukemia. 20 Q. May I ask you what your opinion was in 21 the first case? 22 A. That the levels of benzene to which the 23 plaintiffs were exposed does not constitute a 24 measurable health risk, and in -- do you want to 25 know the second one? Associated Reporters, Inc. (504) 529-3355 44 1 Q. Let me ask you a little bit about that. 2 Was that based on personal monitoring or some other 3 information you had about the actual exposure 4 levels? 5 A. The exposure levels -- it's a water 6 case basically, and the exposure levels have been 7 measured, or the water levels have been measured by 8 EPA. 9 Q. Okay. In what context was there water 10 exposure? 11 A. Well water. 12 Q. Okay. With regard to the other case, 13 what was your opinion? That would be Conde? 14 A. Yes. Basically that the allegations of 15 the plaintiffs with respect to health effects were 16 not related to chlordane exposure. 17 Q. Okay. Have you ever either been 18 retained by or testified on behalf of a plaintiff? 19 A. I have been retained by three 20 plaintiffs. I have not testified on behalf of a 21 plaintiff. 22 Q. Could I ask you then what percentage of 23 your total litigation work has been defense 24 retention and testimony? 25 A. Probably 80 to 90 percent. Associated Reporters, Inc. (504) 529-3355 45 1 Q. About how many litigation cases do you 2 take per year, if you can average it out? 3 A. I prepared, as best as I could, a list 4 of the depositions and trial testimony that I have 5 given. 6 Q. And this starts in 1988? 7 A. Yes. That's the best of my 8 recollection, because I don't keep those records. 9 I just put that together in response to this. 10 Q. And this is, again, based on your 11 recollection, without referring to any specific 12 materials? 13 A. Yes. 14 Q. Did your litigation-based consultation 15 begin then in 1988? 16 A. Yes. 17 Q. And this is the testimony only; it 18 doesn't include the cases where you were retained 19 and did not testify? 20 A. That's correct. 21 Q. Could you give me an estimate of how 22 many additional cases there are under that 23 category? 24 A. That would be -- I really don't have a 25 clear idea on that, because it's very difficult for Associated Reporters, Inc. (504) 529-3355 46 1 me to keep cases straight. Sometimes they are put 2 together; sometimes they are split up. I think 3 more in terms of issues than cases. 4 As I said before, it represents about 7 5 to 10 percent of my time. That's about as good an 6 estimate as I can give you. 7 Q. Okay. I guess I had better put a tag 8 on this. 9 (EXHIBIT NO. 7 WAS MARKED) 10 A. It's highly variable. 11 Q. Do you have any records at all that you 12 keep, routine business records which would indicate 13 the number of times you have been retained? 14 A. No. 15 Q. What kind of bookkeeping do you use to 16 keep track of where you stand with litigation 17 matters? 18 A. You are looking at it. 19 Q. So that all comes from up here, right, 20 indicating your head? 21 A. If I keep a piece of paper on a 22 particular case, when the case is concluded I throw 23 the paper away, along with virtually everything 24 else that I receive; otherwise I would be buried in 25 paper. Associated Reporters, Inc. (504) 529-3355 47 1 Q. So you don't keep the depositions or 2 anything? 3 A. No. 4 Q. Referring to Exhibit 7, is there any 5 way you can break down the cases in terms of either 6 disease process or chemical involved? I should say 7 chemical or causative agent. 8 A. Chronic myelogenous leukemia, benzene; 9 acute myelogenous leukemia, benzene. 10 Q. When you say AML and benzene, are you 11 talking about the second case there? 12 A. Yes. 13 Q. Okay. 14 A. Chronic lymphocytic leukemia, 15 non-Hodgkin's lymphoma, and angiolymphadenopathy. 16 The allegation there was benzene. 17 Q. Are we on the fifth one now? 18 A. Fourth one. Chronic lymphocytic 19 leukemia and benzene. 20 Q. That would be the fifth one? 21 A. That's the fourth one. 22 Q. Okay. 23 A. Chlordane and rash, eczema. Excuse me. 24 I take it back. I have testified in a plaintiff's 25 case. That makes four plaintiffs' cases. Associated Reporters, Inc. (504) 529-3355 48 1 Q. Which one was that? 2 A. Anschutz versus National Lead, and the 3 issue was lead contamination. 4 Q. Water? Airborne? 5 A. Ground. 6 Q. Ground? 7 A. Chronic lymphocytic leukemia, and I 8 think it was butadiene; could have been benzene, 9 could have been both. 10 Q. Which case is that? 11 A. Chambers. Myelofibrosis and butadiene; 12 non-Hodgkin's lymphoma and benzene; benzene and a 13 variety of complaints that could best be described 14 as immune dysfunction. I even hate to say the 15 word. 16 Q. Which case was that? 17 A. Albertson versus KNE. And as I 18 mentioned, Conde was chlordane and a variety of 19 complaints. 20 Q. Was your opinion in each of those 21 cases, save for the Anschutz case or the lead case, 22 that there was no relationship between the disease 23 process and the alleged causative agent? 24 A. Yes. Excuse me. That's not entirely 25 true. For AML and benzene, that is not my opinion. Associated Reporters, Inc. (504) 529-3355 49 1 Q. So you find there is a causal 2 connection between AML and benzene? 3 A. Benzene exposure, high levels of 4 benzene exposure. 5 Q. High levels only? 6 A. Yes. It's a dose-related phenomenon. 7 Q. Would the dose be dependent upon the 8 intensity of individual exposure or the duration of 9 exposure or both? 10 A. Both. 11 Q. Let me ask you as a group. In your 12 opinion, would benzene, butadiene, ethylene 13 oxide -- and I will limit it to those three for 14 this deposition -- be classified as carcinogens? 15 A. They would all three be classified as 16 animal carcinogens. 17 Q. In the human context, would they be 18 classified as carcinogens? 19 A. Benzene is classified as a human 20 leukemogen. The other two are not. 21 Q. Would that represent a presently 22 existing conclusion based upon the state of the 23 research into butadiene and ethylene oxide as far 24 as causation is concerned? 25 A. Certainly in terms of my opinion, Associated Reporters, Inc. (504) 529-3355 50 1 that's the case. As far as what they are 2 classified on by other agencies, I think it's fair 3 to summarize the state of the art in that since 4 there is sufficient animal data for butadiene, and 5 arguably sufficient animal data for ethylene oxide, 6 that they would in regulatory terms be classified 7 as probable or suspect human carcinogens, simply 8 because there is sufficient evidence in animals. 9 Q. So you are talking about as far as OSHA 10 or EPA would be concerned? 11 A. EPA, not OSHA. 12 Q. And that would be your understanding of 13 how they would characterize butadiene and ethylene 14 oxide? 15 A. Yes. 16 Q. Is benzene a complete carcinogen in 17 terms of leukemia or bone marrow processes? 18 A. I believe the term is misleading, an 19 oversimplification of the case, but in the context 20 of chronic exposure to benzene, by itself, lead to 21 the development of AML, the answer is yes. 22 Q. Are you limiting that solely to AML? 23 A. Yes. 24 Q. It doesn't move to CML; it doesn't move 25 to any of the other leukemias? Associated Reporters, Inc. (504) 529-3355 51 1 A. There is no evidence to support that. 2 Q. Okay. 3 A. Obviously there are several variants of 4 AML that are included in that grouping. When I 5 talk about AML, I am talking about the major 6 variants of AML as well, for the most part. 7 Q. And I think early on we established 8 your opinion, but let me get it again. Any of the 9 three chemicals, benzene, butadiene and ethylene 10 oxide; what's your opinion to a reasonable degree 11 of scientific certainty as to whether or not they 12 are capable of inducing a multiple myeloma in a 13 human being? 14 A. There is not sufficient scientific or 15 medical evidence to support that conclusion. 16 Q. Would you consider butadiene or 17 ethylene oxide to be a promoter of a multiple 18 myeloma? 19 A. No. I think that's a misstatement. 20 There are no initiation-promotion paradigms for any 21 leukemia or lymphoma model in man or experimental 22 animals. If you look at the characteristics of the 23 promoters that have been studied in typical liver 24 and skin tumor models, these compounds don't have 25 any of the characteristics of promoters. There is Associated Reporters, Inc. (504) 529-3355 52 1 no evidence to even, I think, support any 2 speculation of butadiene as a promoter. 3 Q. Okay. Is butadiene known to cause any 4 disease in man? 5 A. No. 6 Q. Is ethylene oxide known to cause any 7 disease in man? 8 A. It can cause toxicity, especially at 9 high doses. 10 Q. Toxicity would be a non-malignant type 11 reaction? 12 A. Yes. 13 Q. Would that be liver toxicity? 14 A. To the best of my recollection, acute 15 exposure may cause some respiratory distress. It's 16 going to cause some hemolytic anemia and some 17 problems associated with red cell function and 18 metabolism. It will lead to an anemia. 19 Q. Would it be your testimony then that 20 butadiene is not a potentially harmful substance 21 when it results in exposure to human beings? 22 MS. ARRAS: I am going to object to the 23 form. 24 BY MR. FLERLAGE: 25 Q. If you can answer it. Associated Reporters, Inc. (504) 529-3355 53 1 A. As a toxicologist, I don't think there 2 is any non-toxic substances. I think everything is 3 toxic, including water. It depends on root. It 4 depends on dose. It depends on the specific 5 condition under which the exposure occurs. 6 I think that the epidemiology 7 associated with butadiene toxicity in man, 8 especially as it relates to carcinogenesis, is 9 inconsistent. It is confusing. It is inadequate, 10 and it does not establish a clear pattern of 11 anything, which is what I think the state of the 12 art is today. 13 Q. Do you intend to speak to state of the 14 art in terms of when it was known or when it should 15 have been known within industry that benzene was a 16 potentially harmful substance? 17 A. A potentially harmful substance? 18 Q. Yeah. 19 MS. ARRAS: I am going to object to the 20 form. 21 A. As I said before, I think everything is 22 a potentially harmful substance. It's a matter of 23 dose. It's a matter of root. It's a matter of 24 regimen. From that standpoint, it becomes -- I 25 find it difficult to answer your question globally. Associated Reporters, Inc. (504) 529-3355 54 1 Q. Are you familiar with the API report on 2 benzene, which came out in 1948 I believe? 3 A. I am sure I have seen it. 4 Q. Okay. If in that report benzene was 5 described as a toxic substance, would that indicate 6 a certain state of knowledge of the API with regard 7 to the potential harmful effects of exposure to 8 benzene? 9 A. First of all, I wouldn't consider that 10 document to be authoritative with respect to the 11 science. Second of all, I think it's clear that 12 throughout the '30s, '40s, '50s, and even the '60s, 13 there is a body of literature that grew to indicate 14 that benzene in high concentrations caused blood 15 dyscrasias, bone marrow suppression, aplastic 16 anemia, thrombocytopenia, a variety of 17 abnormalities associated with that. I don't think 18 that's an issue. The issue is the dose and what 19 those abnormalities were. 20 Q. Is that a sufficient body of 21 information to cause a reaction among industry 22 members to take precautions against potentially 23 toxic exposures to benzene? 24 A. I think that if you have knowledge of 25 potential toxicity associated with any exposure Associated Reporters, Inc. (504) 529-3355 55 1 scenario, regardless of whether it's benzene or 2 anything else, that it is prudent to take steps to 3 limits those exposures. The question is one of 4 threshold and one of dose. 5 Q. Are you aware of what steps were taken 6 by industry in general to determine what the toxic 7 levels of benzene exposure would have been in let's 8 say the '30s and '40s? 9 A. I am aware of literature. Other than 10 that, I am not aware of anything besides what 11 appeared in the published literature. 12 Q. And what published literature are you 13 referring to, if you can be specific at all? 14 A. The sum total case reports, isolated 15 case reports, as well as the collections of cases 16 and the epidemiology studies that followed them. 17 We are not talking about a specific 18 point in time when recognition of toxicity 19 occurred. Science doesn't work that way. I think 20 it's fair to say that by the '60s, there was an 21 appreciation that benzene could cause bone marrow 22 suppression. That's the sum total accumulation of 23 a lot of different reports in different 24 publications. 25 Also, the whole process of recognizing Associated Reporters, Inc. (504) 529-3355 56 1 the toxicity of benzene and what its potential 2 toxicity was coincided with an increase in 3 sophistication in hematology in general. 4 Q. I don't want to put words in your 5 mouth, but are you referring to individual case 6 studies of the incidence of leukemia and 7 benzene-exposed populations during the 1930s and 8 '40s when you talk about existing bodies of 9 literature? 10 MS. ARRAS: I am going to object to the 11 form. 12 A. There are isolated case reports which 13 began to appear in the '30s. The very first 14 controlled study that was ever done, and it's by no 15 means a paradigm of experimental design, is a study 16 by Goldwater, et al, looking at the lithography 17 industry in New York. That was 1939-1941. That 18 study demonstrated that under high levels of 19 exposure, benzene could cause bone marrow 20 suppression. 21 And as I said, without referring back 22 to the literature, I can't tell you the specific 23 number of cases, but there were cases reported by 24 Hunter. There were cases that were reported 25 earlier than that, one or two here and there, a Associated Reporters, Inc. (504) 529-3355 57 1 handful, and that continued up through the '60s. 2 An individual case doesn't really 3 provide you with I think sufficient information to 4 draw a conclusion. All it can do is draw attention 5 to a potential problem. Certainly by the mid '60s, 6 there was reason to be concerned about high-level 7 exposure to benzene. 8 Browning, in 1965, published a 9 collection of cases that certainly was not 10 definitive or controlled, but provided sufficient 11 evidence that there was something to be concerned 12 about and that it should be studied. 13 About the same time, the late '60s, we 14 have studies coming out of Italy and Turkey. 15 Vigliani published a collection, again, of cases; 16 not controlled, but nevertheless pointing a finger 17 at benzene and high-level exposure in terms of -18 now we are talking about not only bone marrow 19 suppression, but also leukemia. 20 The issue of bone marrow suppression I 21 think is one that people began to realize was a 22 problem somewhere between the '40s and the '60s. 23 Certainly by the mid '60s it was established. 24 Q. As a toxicologist, given an 25 understanding of potential danger to high-level Associated Reporters, Inc. (504) 529-3355 58 1 exposure to benzene, what in your opinion should 2 have been done to protect people exposed to high 3 levels of benzene in industry? 4 MR. McCALL: I am going to object to 5 the form of the question, Counsel, as 6 overlybroad. I mean the use of the 7 term "industry" without any further 8 definition and identification of what 9 people you are talking about, I think 10 that's just objectable as to form 11 MR. SPEARS: I would echo that, and 12 also you didn't qualify it as to what 13 point in time we are talking about. 14 1990s? '80s? 1800s? What are we 15 talking about? 16 MS. ARRAS: I also object that it's 17 beyond the scope of the witness' 18 expertise. 19 BY MR. FLERLAGE: 20 Q. Can you answer it? 21 A. Could you state the question again? 22 Q. I think I better have it read back. 23 (RECORD READ BACK BY REPORTER) 24 A. As a toxicologist, I am neither an 25 engineer, nor am I an industrial hygienist, so I Associated Reporters, Inc. (504) 529-3355 59 1 cannot speak to specific measures that should or 2 should not be taken. But I think that the basis of 3 your question -- your question formulates the basis 4 of my answer, and that is to eliminate high-level 5 exposure. I mean it's not rocket science. 6 Q. Okay. Exposure; we keep talking about 7 exposure. What are the methods by which persons 8 can become exposed to benzene? 9 A. Certainly at high levels or significant 10 levels, exposure is usually associated with 11 contingent events, whether they be fugitive 12 emissions or spills or leaks or misuse of the 13 chemical. Certainly in terms of cumulative risk 14 assessment, there is a great deal of concern in 15 many circles today over a chronic level of exposure 16 from water or air, cigarette smoking, a variety of 17 other sources. 18 Q. Bottom line is you either breath it in 19 or you absorb it through your skin or you ingest it 20 somehow? 21 A. Those are the principal routes. I 22 think that under most circumstances the major root 23 for significant absorption of benzene is 24 inhalation. Even in the context of skin exposure, 25 the situation almost always favors inhalation as Associated Reporters, Inc. (504) 529-3355 60 1 the major root. 2 Q. Are benzene metabolites created by the 3 body within the lungs and the liver? 4 A. Predominantly the liver. One could 5 argue or speculate as to the role of the lung, but 6 I think the liver is by far the most important. 7 Q. And the roots by which benzene reaches 8 the liver would be any of the three that we have 9 talked about; that would be ingestion, absorption 10 or inhalation? 11 A. Yes. There are some differences. 12 Obviously, in terms of those roots, there are some 13 subtleties. But certainly in the case of 14 inhalation, the liver is the principal metabolic 15 organ, and even for ingestion, you are going to 16 have a first pass effect, but still, the liver is 17 going to be the first order. 18 Q. Is there any indication that the bone 19 marrow itself creates the metabolites that cause 20 the damage done in the bone marrow? And I am 21 talking about benzene right now. In other words, 22 does the benzene itself, as benzene, reach the bone 23 marrow, and can it be metabolized therein? 24 A. I have done some early work looking in 25 rats with respect to the innate ability of the bone Associated Reporters, Inc. (504) 529-3355 61 1 marrow to metabolize benzene, and if my 2 recollection is correct, it's on the order of 3 1/10,000 of a percent of the rate of metabolism 4 that goes on in the liver. 5 I think there is some evidence to 6 suggest that you can actually measure benzene 7 metabolism detected in human bone marrow. But by 8 the same token, that's not been really thoroughly 9 studied, and one of the reasons is because it is 10 such a minor source for metabolism. Certainly in 11 all the studies of toxicity that I am aware of, the 12 influence of metabolism on toxicity is due to the 13 liver. 14 Q. Okay. The reason I asked those 15 questions is I wanted to find out if there is a 16 difference or if it's understood that there is a 17 difference between the way butadiene and/or 18 ethylene oxide would be metabolized by the body. 19 A. Well, I haven't really finished benzene 20 yet. 21 Q. I'm sorry. Go ahead, any way you want 22 to answer it. 23 A. You are dealing with a very complex 24 issue. In the case of benzene, primary metabolism 25 occurs in the liver. This is a detoxification Associated Reporters, Inc. (504) 529-3355 62 1 process primarily. 2 At the same time, you have secondary 3 metabolism at the level of the bone marrow, and I 4 think tertiary metabolism at the level of the bone 5 marrow. This is very important, because in the 6 absence of that metabolism you are not going to get 7 the pattern of metabolite accumulation in the bone 8 marrow that you do, which makes the bone marrow a 9 target for benzene. And it's those secondary 10 metabolites and that secondary, tertiary metabolism 11 that's important. 12 In the case of butadiene, we have 13 evidence to suggest that butadiene is metabolized, 14 certainly in the mouse, in both the liver and the 15 bone marrow. It may be metabolized in other organs 16 as well. It is not metabolized by the same enzyme 17 systems per se. It's a totally different animal 18 with respect to metabolism. 19 Ethylene oxide is a direct acting 20 compound and does not require metabolism to produce 21 toxicity directly. What that means is, obviously, 22 if you get ethylene oxide to a site, it has the 23 potential to react with those molecules, but there 24 are a sea of molecules it's going to encounter 25 en route, and so the primary effects of ethylene Associated Reporters, Inc. (504) 529-3355 63 1 oxide are going to be more proximate than the 2 primary effects of butadiene or benzene. 3 Q. Would the butadiene and/or ethylene 4 oxide metabolites, which in the case of at least 5 ethylene oxide do happen to reach the bone marrow, 6 assuming they did, would they react on the same 7 cells that the benzene metabolites react on, 8 initially? 9 A. It's not so much a function of reaction 10 on -- I mean if a compound is present and a cell is 11 present, there is potential for a reaction. But in 12 general, when you look at differential toxicity, 13 what you find is it's the susceptibility of 14 individual cells and their capability to either 15 activate or detoxify that molecule that determines 16 their susceptibility and what the pattern of 17 toxicity will be. It just isn't simply getting a 18 molecule to a given cell. That plays a role, but 19 it is only one step in the process. 20 Q. Am I given to understand from your 21 testimony that detoxification is more complete in 22 the cases of butadiene and ethylene oxide than it 23 would be in the case of benzene? 24 A. No, not -- it depends upon what 25 question you are asking. I am saying that the Associated Reporters, Inc. (504) 529-3355 64 1 delivery of a molecule that can react potentially 2 with a cell to a given cell is dependent on, one, 3 its initial reactivity. If I mean if it's so 4 reactive -- if you, for instance, inhale an 5 extremely -- let's take hypothetically a very 6 reactive molecule, and ethylene oxide is certainly 7 a reactive molecule. 8 To speculate on its reaching a site 9 such as the bone marrow in sufficient concentration 10 to produce toxicity is a much greater reach than it 11 is for something like benzene, where benzene itself 12 is not toxic, except when it becomes a solvent, in 13 extremely high concentrations. It has to be 14 metabolized in the liver. The metabolites are 15 relatively stable. They can be transported to the 16 bone marrow, where they can undergo secondary 17 metabolism to form highly reactive metabolites that 18 are not stable and can't move around. 19 As I said, it becomes a very complex 20 issue, and it's hard to generalize. If you ask a 21 specific question, I can do any best to address it, 22 but it's hard in global terms to describe 23 individual features that will allow to you predict 24 the toxicity of a given compound. 25 Q. Let's put it in terms of leukemia, AML; Associated Reporters, Inc. (504) 529-3355 65 1 does ethylene oxide, in your opinion, cause 2 leukemia? 3 MR. McCALL: Are you saying "AML"? 4 BY MR. FLERLAGE: 5 Q. Let's make it AML. 6 A. I think the evidence for ethylene oxide 7 causing leukemia in man is insufficient and 8 contradictory. We have some relatively small 9 studies, actually very small studies, that don't 10 really evaluate exposure well, certainly in the 11 initial case, and that are not very well 12 controlled, that have an extremely low incidence. 13 In fact, I think we are talking in the initial 14 paper approximately one leukemia and one lymphoid 15 neoplasm that was reported. 16 And on the other hand, we have a study 17 by Morgan which basically refutes that, that finds 18 no relationship between ethylene oxide and 19 hematopoietic or lymphoid neoplasms. We have 20 confounding exposure scenarios, certainly in the 21 first case, and on the basis of that literature I 22 don't think you can draw a conclusion that in fact 23 ethylene oxide is associated with hematopoietic or 24 lymphoid neoplasms. 25 Q. That's based on epidemiology, though? Associated Reporters, Inc. (504) 529-3355 66 1 A. Yes. It's not based on mechanistic 2 studies of either animals or human experience? 3 A. I think the animal studies don't help 4 us, certainly not to date. I don't think they 5 allow us to draw that conclusion or to support or 6 refute the epidemiology. 7 In order to do mechanistic studies, you 8 have to frame a fairly well-focused hypothesis, 9 which means you have to have a relationship that 10 you can then test. I don't think the epidemiology 11 studies bring us to that point with ethylene oxide. 12 (OFF THE RECORD DISCUSSION) 13 BY MR. FLERLAGE: 14 Q. I do want to try and ask you that same 15 question, limiting it to AML. Does butadiene cause 16 AML? 17 A. I don't think that there is sufficient 18 evidence to indicate that it does. I think you 19 have very conflicting literature base. You have an 20 initial study that did not have sufficient power to 21 answer the question, but suggested there might be 22 an increase. 23 You have got other studies that 24 actually see a deficit of AML. You have got a 25 study that saw no increase in AML in a Associated Reporters, Inc. (504) 529-3355 67 1 retrospective cohort, and then perhaps an increase 2 in a subpopulation in a case-control. 3 Based on the power of that study, those 4 two findings are inconsistent, and probably have to 5 do with problems of assignment in exposure 6 category. At the present time, I don't think there 7 is sufficient pattern or consistency in the 8 epidemiologic literature to say anything about 9 butadiene. 10 Q. Is there a sufficient mechanistic study 11 of the metabolic processes of butadiene to arrive 12 at a conclusion as to whether it's metabolized the 13 same way as benzene is? 14 A. It's not. 15 Q. In what ways is it different? 16 A. Well, it doesn't form the same 17 molecules. It has a totally different metabolic 18 pathway. 19 The initial metabolism of butadiene 20 involves the primary hydroxylation or epoxidation 21 to form a monoepoxide, epoxibutene. Secondary 22 metabolism after that I think is not at all well 23 characterized. I think the literature that's out 24 there to date is probably, for the most part, 25 erroneous with respect to the role of secondary Associated Reporters, Inc. (504) 529-3355 68 1 metabolism of butadiene, and that is part and 2 parcel of what we are researching at the present 3 time. 4 Q. So there is no determination, no 5 conclusion as to whether the metabolites of 6 butadiene are capable of reaching the bone marrow; 7 is that the idea? 8 A. No. I think that there is certainly 9 evidence in the mouse that the primary metabolite 10 does reach the bone marrow, and it does produce 11 some relatively specific effects on bone marrow 12 cells. We haven't completed those studies, but it 13 certainly looks as though it has some effects. 14 They are totally different than benzene. 15 Q. In other words, the effects are 16 totally different than benzene? 17 A. The cell types and the responses that 18 are seen in those cells are different. And 19 certainly from a mechanistic standpoint, butadiene 20 and benzene are not mechanistically linked. 21 Q. Okay. 22 A. So I would not, as a matter of fact, 23 expect to see the same pattern of toxicity in man. 24 Q. Okay. Doctor, from your review of the 25 information that you received from counsel with Associated Reporters, Inc. (504) 529-3355 69 1 regard to the employment backgrounds of Mr. LeBlanc 2 and Mr. Stelly, do you have an opinion to a 3 reasonable degree of scientific certainty as to 4 whether, first of all, Mr. LeBlanc was exposed to 5 benzene during his career? 6 A. Could I see my notes? 7 Q. Sure. Help yourself. Here they are 8 right here. 9 A. Well, to clarify, let me clarify one 10 issue. Benzene is ubiquitous. If you are going to 11 talk about exposure, we have all been exposed. 12 Q. How about occupationally exposed? 13 A. I have no information that's been 14 provided to me that would lead me to reach a 15 conclusion as to any exposure to benzene from an 16 occupational standpoint. 17 Q. Either way; he was not or he was? 18 A. That's correct. 19 Q. Would the same be true then in 20 Mr. LeBlanc's case for butadiene and ethylene 21 oxide? 22 A. Yes. To the extent that I find no -23 there is no evidence that I have seen in terms of 24 their depositions that allow me to reach a 25 conclusion that they have been exposed to Associated Reporters, Inc. (504) 529-3355 70 1 significant levels of these agents. 2 Q. That would be all three of the agents; 3 benzene, butadiene, ethylene oxide? 4 A. Yes. 5 Q. Is there information which would lead 6 you to conclude that Mr. LeBlanc was not exposed to 7 any of the three substances? 8 A. Again, you can't prove a negative, 9 certainly from a scientific standpoint, so I am 10 certainly not going to generalize that they have 11 never been exposed to these agents. I just said, 12 for instance, that everyone has been exposed to 13 benzene. Everybody has mostly likely been exposed 14 to ethylene oxide. The only one that I would say 15 there is not a great deal of opportunity for 16 exposure in the general population is butadiene. 17 Q. Doctor, to the best of your knowledge, 18 was Mr. LeBlanc's case originally in with the Ellis 19 group? 20 A. I have no idea. 21 Q. There was one thing in this deposition 22 that was puzzling to me. 23 MS. ARRAS: Perhaps we could clarify; 24 that was Maxie LeBlanc. 25 MR. FLERLAGE: That was a different Associated Reporters, Inc. (504) 529-3355 71 1 LeBlanc? 2 MS. ARRAS: Yes. 3 MR. FLERLAGE: Oh, okay. Thank you. 4 So there were two LeBlancs we are 5 talking about then. It wasn't on the 6 caption anywhere, and I just didn't 7 know. 8 BY MR. FLERLAGE: 9 Q. Okay. In Mr. LeBlanc's case, from the 10 information you received either from in his 11 deposition or from counsel in summary form, can you 12 tell me where Mr. LeBlanc was employed, where he 13 would have been exposed occupationally to benzene 14 or potentially could have been exposed to benzene? 15 MS. ARRAS: I believe the doctor has 16 testified that he doesn't see the 17 evidence of exposure to benzene in the 18 records, so therefore it would be 19 difficult for him to answer where he 20 thought there was exposure. 21 BY MR. FLERLAGE: 22 Q. Is that a fair summary of what you 23 said, Doctor, that you can't find any evidence that 24 he was exposed to benzene? 25 A. I don't find any evidence that would Associated Reporters, Inc. (504) 529-3355 72 1 lead me to be able quantify or qualify his exposure 2 to benzene in an occupational setting. 3 Q. Well, that's different than counsel 4 just said, quantify or qualify. Quantify means put 5 a number on the level of exposure? 6 A. Or make any statement whatsoever with 7 respect to whether it was a little, none, trivial, 8 a lot, more. I mean there is just no -- I have no 9 data. 10 Q. What was Mr. LeBlanc's trade? 11 A. He was involved in construction, 12 primarily roofing, both resident and commercial. 13 He did some carpentry, but not in the context of 14 working in commercial plants. He worked in 15 pipewrapping and in roofing for various periods of 16 time. 17 His exposure history with respect to -18 occupational history with respect to the petroleum 19 industry and chemical industry appears to be 20 primarily from 1962 to 1985. During that period of 21 time, he worked only part-time as a contractor at 22 those facilities, and he spent about half of his 23 time doing roofing. 24 Q. Based upon your review of the records 25 of deposition materials and other summary materials Associated Reporters, Inc. (504) 529-3355 73 1 provided from counsel then, your assessment of his 2 potential exposure to benzene would be limited to 3 that time period, '62 through '85? And I am 4 talking, again, about occupational exposure. I 5 left that out. I'm sorry. 6 A. I don't think that's a fair statement 7 either, because certainly in the roofing trade, 8 working with tar pitch, asphalt, petroleum 9 distillates, what have you, since the '40s, the 10 potential for exposure to a wide variety of agents, 11 including benzene, would exist in that environment, 12 independent of the exposure that took place or that 13 could have taken place between 1962 and 1985. 14 Q. Did Mr. LeBlanc perform any 15 pipewrapping which involved the use of asphalt at 16 the plants, the petroleum or chemical plants that 17 are involved in this case? 18 A. He described pipewrapping that involved 19 the use of a product that required high heating in 20 order to apply it, and I suspect that that was 21 either a tar pitch or asphalt-based product. 22 That's the extent of my knowledge. 23 Q. You wouldn't know the chemical makeup 24 of that substance then? 25 A. I vaguely remember some discussion of Associated Reporters, Inc. (504) 529-3355 74 1 it in his deposition, but I don't recall at the 2 present time. 3 Q. Did Mr. LeBlanc do any asphalt-based 4 roofing or tar pitch-based roofing at any of the 5 chemical or petroleum plants involved in this case? 6 A. That is my understanding. 7 Q. And what then is your understanding of 8 the type or extent of such work that he did at 9 these plants? 10 A. Again, it's very vague, but my 11 recollection is that it was approximately 50 12 percent of his time. 13 Q. Are you able to conclude from the, as 14 you describe it, I guess limited information that 15 you have got on exposure that Mr. LeBlanc's 16 exposure to asphalt or tar pitch during those 17 periods of time that you have described was a 18 potential cause of his disease process? 19 A. I think the sum total of epidemiologic 20 evidence with respect to occupational exposure and 21 multiple myeloma allows one to make a clear 22 assignment of causation to radiation exposure, 23 gamma radiation. 24 I think that as of today, there is 25 probably sufficient evidence to link farming and Associated Reporters, Inc. (504) 529-3355 75 1 work with animals to multiple myeloma. When you 2 get beyond that, you get into the area of 3 hypothesis, where there have been various 4 relationships suggested in various studies, others 5 in others, and you have an inconsistent database 6 with respect to the relationship between exposure 7 in a given situation and development of multiple 8 myeloma. 9 I would say that with respect to the 10 hypothesis that benzene causes multiple myeloma or 11 that exposure to benzene does, and the evidence to 12 support that, there is such just as much evidence 13 to link exposure to coal tar-based products; 14 asphalt, pitch. 15 There is actually evidence in the 16 literature to suggest that exposure to vitamin C or 17 laxatives actually has a higher association or a 18 greater association with multiple myeloma than 19 benzene. 20 I think it's arguable for any of these 21 various hypotheses whether there is a causal 22 relationship. It's the weight of the evidence and 23 the quality of the evidence, and I don't think the 24 evidence supporting benzene is any stronger than 25 the evidence supporting coal tar or the evidence Associated Reporters, Inc. (504) 529-3355 76 1 supporting a variety of other alleged potential 2 relationships. 3 Q. Is there in there any evidence that 4 Mr. LeBlanc used laxatives regularly during his 5 life? 6 A. I don't recall any information on that 7 from his record. 8 Q. Is there any evidence in the case that 9 Mr. LeBlanc was exposed to radiation during his 10 career? 11 A. He was exposed to radiation therapy 12 after diagnosis, but I have no knowledge of 13 radiation exposure prior to that. 14 Q. Okay. Is there any way you can arrive 15 at a conclusion that the combination of his 16 exposures that we have described, whether it be 17 coal tar or tar pitch or asphalt and benzene, while 18 working at one of these plants, the combination of 19 those two, may be causative or the combination of 20 those may act synergistically in causing his 21 disease process? 22 MR. McCALL: Let me object to the form 23 of the question as a 24 mischaracterization of his prior 25 testimony insofar as referring to Associated Reporters, Inc. (504) 529-3355 77 1 benzene as a cause. 2 BY MR. FLERLAGE: 3 Q. Let me retry the question. Assuming 4 that Mr. LeBlanc was occupationally exposed to 5 benzene during his career, and assuming that he was 6 exposed to asphalt and tar pitch during his career, 7 as you have described from the deposition and what 8 have you, are you able to state to a reasonable 9 degree of scientific certainty as to whether there 10 might be a synergistic relationship between the two 11 substances in causing his multiple myeloma? 12 MR. McCALL: Let me object to the form 13 again as assuming facts not in 14 evidence. 15 MS. ARRAS: I join. 16 A. No. It would be wild speculation to 17 attempt to hypothesize interactions between those 18 compounds. I don't think that the database 19 literature with respect to epidemiology would allow 20 you to make any association like that. 21 My own personal experience in the last 22 few years with respect to mechanistic research 23 doesn't support that either. My experience is that 24 the responses and the effects that various 25 compounds have on cells within the hematopoietic Associated Reporters, Inc. (504) 529-3355 78 1 and lymphoid system are highly specific, and you 2 cannot predict interactions similarly on the basis 3 of hypothesizing that two compounds may have the 4 same target tissue. 5 Q. Now was Mr. LeBlanc a smoker? 6 A. I believe he was. 7 Q. Can you put it into packs per day or 8 pack-year history? 9 A. I didn't do that. 10 Q. Can you remember whether or not he was 11 a heavy smoker, moderate, light smoker, at least 12 from what you can remember of the information? 13 A. No. 14 Q. Do you remember what tobacco products 15 he may have smoked? 16 A. I believe it was cigarettes, but I 17 don't recall specifically. 18 Q. Is smoking history at all important as 19 a consideration in determining whether or not any 20 of his occupational exposures caused his multiple 21 myeloma? 22 A. With respect to smoking history, I 23 would say that it's only important with respect to 24 comparative exposure. If you are going to allege 25 or hypothesize that low level or ambient exposure, Associated Reporters, Inc. (504) 529-3355 79 1 cumulative exposure to a compound such as benzene 2 or butadiene plays a role in causation, then I 3 think one has to take into account smoking history. 4 In that context, smoking becomes probably the most 5 significant source of cumulative exposure to either 6 of those two compounds. From the standpoint of 7 causation and biology, no, I don't think that 8 that's an issue. 9 Q. Okay. I guess I better ask, to a 10 reasonable degree of scientific certainty, do you 11 have an opinion as to whether cigarette smoking 12 played a role in Mr. LeBlanc's multiple myeloma? 13 A. I'm sorry. Could you reread the 14 question? 15 Q. Let me just do it again, okay? To a 16 reasonable degree of scientific certainty, do you 17 have an opinion as to whether Mr. LeBlanc's smoking 18 history played a role in the causation of his 19 multiple myeloma? 20 A. For multiple myeloma, there is no 21 evidence to support or refute that. 22 Q. Now you have talked about exposure to 23 animals as being epidemiologically associated with 24 multiple myeloma in human beings; is that correct? 25 A. Yes. Associated Reporters, Inc. (504) 529-3355 80 1 Q. Okay. Mr. Stelly; do you have a 2 history on Mr. Stelly? 3 A. Yes. 4 Q. Do you find any evidence in his history 5 of exposure to animals? 6 A. Yes. 7 Q. Is that important in your consideration 8 of causation of his multiple myeloma? 9 A. I think the evidence to support 10 association with farming, ranching and exposure to 11 domestic animals is probably more impressive than 12 the evidence for any of the other causes we have 13 talked about, with the exception of radiation. 14 So certainly as far as assigning a 15 potential causation or a potential cause for the 16 development of his multiple myeloma, that certainly 17 is one that would be high on my list. 18 Q. From the history you received of 19 Mr. Stelly, and I am limiting it to work history or 20 exposure history right now, can you tell me how 21 long he was exposed to ranching or farming? 22 A. Well, from his deposition, he worked in 23 his early years with his father on a dairy. In 24 1947, after graduating from high school, he was 25 involved in ranching, vaccination, dipping cattle. Associated Reporters, Inc. (504) 529-3355 81 1 He was basically working as a rancher with cattle. 2 At various other times in his career he 3 worked with animals. In 1960 to '61, he was a 4 ranch foreman, worked with cattle. He had a horse 5 accident in 1986, so my assumption is that he has 6 probably spent the greater part of his life in 7 intimate contact with animals, although the times 8 that I have mentioned were times when he worked 9 full-time in that industry. 10 Q. Can you assign a duration to the 11 exposure to animals that Mr. Stelly would have 12 sustained during his life? 13 A. Not accurately. I think it's obviously 14 very significant prior to high school, and he 15 worked full-time in 1947 in ranching. Then he 16 worked again full-time in 1960 in ranching. 17 Q. Is that a significant enough exposure 18 to animals to induce a multiple myeloma in a human 19 being? 20 A. I think if you look at the 21 epidemiologic literature, assigning a quantitative 22 value to that kind of exposure is extremely 23 difficult, because there are any number of 24 different exposures that one could hypothesize are 25 involved. Associated Reporters, Inc. (504) 529-3355 82 1 It's been hypothesized for years that 2 ranching involves antigenic stimulation. It 3 involves exposure to fertilizer. It involves 4 exposure to feces and animals, viruses, to 5 pesticides and a variety of other very complicated 6 chemical exposure and agent exposure scenarios. 7 At this point in time, I don't think 8 that it's possible to assign a quantitative value 9 to a given exposure. I think all one can conclude 10 is that there does appear to be a growing 11 appreciation, both quantitatively as well as 12 qualitatively, of a relationship between multiple 13 myeloma and the farming industry, and he has been 14 involved in that industry. 15 It's not trivial; it wasn't a day or a 16 week or a month. He has had considerable 17 experience in the ranching and dairy industry. 18 Q. But what I am getting at is are you 19 going to state an opinion that his animal or farm 20 exposure is what caused his multiple myeloma? 21 A. I am simply saying that if you are 22 going to attribute a cause to his multiple myeloma, 23 that that would be the first thing on my list. I 24 am not prepared to say that that is the cause of 25 his multiple myeloma. Associated Reporters, Inc. (504) 529-3355 83 1 Q. Okay. Are you able to characterize 2 from Mr. Stelly's occupational history whether or 3 not he was exposed to benzene during his career? 4 A. No. 5 Q. And why is that? 6 A. Again, there is no information, either 7 qualitatively or quantitatively, that I have read 8 in his deposition that would allow me to do that, 9 and I have seen no records of potential exposure 10 that was associated with the activities that he 11 describes. 12 Q. He was a pipefitter; is that correct? 13 A. Yes. 14 Q. Was there any anecdotal information 15 from any source which would describe the types of 16 pipefitting work he did in the chemical and 17 petroleum plants at which he worked? 18 A. Yes. He talked about cracking pipes 19 and occasionally smelling the material that was in 20 the pipes. But there is no way from those 21 descriptions that you can draw any conclusions with 22 respect to benzene exposure or what the levels 23 might or might not have been. 24 Q. Did he describe working on any benzene 25 systems at all in any of the plants? In the Associated Reporters, Inc. (504) 529-3355 84 1 pipefitting sense now I mean. 2 A. I would have to reread it to see if he 3 specifically discussed benzene. I am sure he 4 worked on pipes that had to do with various feed 5 stocks and/or processes that may have contained 6 some benzene, but again, drawing any conclusions as 7 to what that exposure was, you can't do it from 8 what I have read. I certainly can't. 9 Q. In Mr. Stelly's case, is there any 10 evidence that Mr. Stelly may have been exposed to 11 gamma radiation during his career? 12 A. Not to my knowledge. 13 Q. You also received medical records and a 14 medical summary I believe from counsel; is that 15 correct? 16 A. Yes. 17 Q. Do you have an opinion to a reasonable 18 degree of scientific certainty as to whether or not 19 Mr. Stelly, first of all, suffers from multiple 20 myeloma? 21 A. He was diagnosed as having plasma cell 22 myeloma, which I would consider multiple myeloma, 23 same category. 24 Q. So you take no issue with the 25 diagnosis -- Associated Reporters, Inc. (504) 529-3355 85 1 A. No. 2 Q. -- of the disease process? 3 A. No. 4 Q. In Stelly's case? 5 A. That's correct. 6 Q. Mr. LeBlanc, the same questions; do you 7 agree or disagree that he has what would be termed 8 multiple myeloma? 9 A. In terms of what I have seen, again, 10 it's multiple myeloma. I don't have any real 11 problems with that. 12 Q. Will you be rendering any form of 13 opinion with regard to a prognosis for these two 14 gentlemen? 15 A. No. 16 Q. I have asked you a couple of questions, 17 Doctor, about synergy or synergistic relationships. 18 Is there any place in a discussion of multiple 19 myeloma for the concept of synergy between various 20 chemicals or substances? 21 A. I don't think we know enough about that 22 to draw a meaningful conclusion, and it would be 23 rank speculation. You could just as easily, for 24 any of these issues of causation, speculate that 25 there are potential interferences that could play a Associated Reporters, Inc. (504) 529-3355 86 1 role in protecting against the development of the 2 disease. It's a very complicated issue that, from 3 a mechanistic standpoint, I don't think is served 4 by superficial speculation. 5 Q. All right. 6 A. We have no evidence to support that. 7 Q. Doctor, in the case of benzene and AML, 8 at what exposure levels, if you can characterize it 9 in any form, is benzene capable of inducing an AML 10 in a human being? 11 A. I have probably been asked that many 12 times. I couldn't count the number of times. 13 Certainly if you look at the sum total of the human 14 literature; epidemiology studies, case reports, 15 which are usually not very useful, case-control or 16 collections of cases, it's relatively well 17 accepted, generally accepted, that exposure to 18 benzene in concentrations of 100 ppm or greater for 19 a significant period of time, usually on the order 20 of years, in some cases many years, will lead to 21 blood dyscrasias, lead to bone marrow suppression 22 in a majority of individuals so exposed. 23 In a relatively small proportion of 24 those, one will see the development of acute 25 myelogenous leukemia or one of its variants. That Associated Reporters, Inc. (504) 529-3355 87 1 data is not controversial. 2 There is some evidence to suggest that 3 exposures in the range of 50 to 100 parts per 4 million may produce some bone marrow toxicity and 5 might produce AML. I personally am concerned about 6 cumulative exposures in that range, but again, we 7 are talking threshold, so it's not just cumulative 8 exposure. But chronic exposure in the 50 to 100 9 parts per million range is subject for concern. 10 As we go down in concentration, our 11 data becomes much less reliable, much less sound, 12 and much, much sparser, more sparse. There have 13 been allegations and assumptions that exposures in 14 the 25 to 50 ppm range may be capable of causing 15 AML. I think the data is extremely unreliable, and 16 it's very difficult to draw a conclusion. 17 I think that conclusions associated 18 with potential causation below that are virtually 19 speculatation. We really have no data below 10. 20 Between 10 and 25, I think it's highly speculative. 21 So if you are asking me what level 22 causes it, all I can do is really look at the 23 strength, the nature of the evidence. 100, 24 definitely; 50, maybe; between 25 and 10 and 50, I 25 think the data is extremely insufficient to draw a Associated Reporters, Inc. (504) 529-3355 88 1 conclusion. 2 Q. When you are talking about 100 parts 3 per million or 50 or 25 to 50 or 10 parts per 4 million, are you talking about time-weighted 5 averages now? 6 A. Okay. Certainly chronic exposure to 7 100 ppm time-weighted average for any length of 8 time is a hazard. The risk is extremely high for 9 blood dyscrasias, for bone marrow suppression, and 10 in some individuals, there is the potential to 11 develop leukemia. 12 If what you are asking me is do I 13 distinguish between cumulative exposure and actual 14 time-weighted average, yes, I do. Mathematically, 15 it's very expedient, especially in a regulatory 16 context, to discuss cumulative exposure in ppm 17 years. 18 For instance, 100 ppm -- well, that's 19 ridiculous. Let me back off. Let's take 50 ppm 20 years or 75 ppm years. If you are talking about 21 exposure to 75 parts per million for one year as 22 being equal to 1 part per million for 75 years, I 23 will say nonsense. I think 1 part per million for 24 75 years in no way, shape or form has been 25 established as causal, whereas 75 ppm for one year, Associated Reporters, Inc. (504) 529-3355 89 1 I would be concerned about. 2 I think cumulative exposure is 3 misleading with respect to causation. It's a much 4 more complicated picture than that. 5 Q. Isn't there some evidence in research 6 and/or in the literature that repeated smaller 7 exposures in the context of benzene may be more 8 dangerous than one large consolidated exposure? 9 A. Again, I can't make a generalization. 10 If you want to discuss specific levels, even some 11 of my own data suggests that intermittent exposure 12 is probably as important as continuous. I don't 13 think there is any evidence that a single exposure, 14 even at high levels, has associated with benzene 15 the development of leukemia. There is such just no 16 evidence to support that. 17 I think that virtually all the cases 18 that have been described have involved repeated 19 exposure in high concentrations. And intermittent 20 exposure, certainly in animals, can produce as much 21 toxicity as continuous exposure to certain 22 concentrations. There appears to be a threshold 23 effect there as well, and that's in terms of 24 toxicity. 25 Q. Would it be fair to say that Associated Reporters, Inc. (504) 529-3355 90 1 benzene-induced cancers such as AML would be 2 dose-response diseases? 3 A. Yes. 4 Q. So is there any understanding of at 5 what dose, quantifiable dose, the body cannot 6 detoxify the benzene? 7 A. What you are talking about is 8 threshold, and that's the issue we have just been 9 discussing. 10 Q. Yeah. You can't put a number on that, 11 though? 12 A. No. 13 Q. Is there any safe exposure to benzene? 14 MS. ARRAS: I am going to object to the 15 form of the question. 16 A. Well, let me put it this way; we are 17 all exposed to benzene in finite amounts in our 18 daily life, and we don't all die of leukemia or AML 19 or have blood dyscrasias, so obviously there are 20 exposure levels to benzene that are not associated 21 with these diseases. When you get into the issue 22 of risk, you get into regulatory issues of 23 prioritization of research and exposure issues that 24 really don't have anything to do with causation. 25 Do I think that it's a good idea to be Associated Reporters, Inc. (504) 529-3355 91 1 exposed to benzene? No, but we are every day and 2 have been throughout history, so I mean it's not 3 a -- I don't think it's really a meaningful 4 question in that context. There is obviously a 5 level of exposure that's not associated with the 6 development of these diseases. 7 Q. As a toxicologist, can you tell me what 8 that level is? 9 A. I wish I could. 10 Q. As a toxicologist, do you take issue 11 with the regulatory agencies setting limits for 12 occupational exposure to benzene? 13 A. No. 14 MS. ARRAS: I object to the form. 15 A. No, that's a policy. That's not an 16 issue of causation. The mandate for regulation is 17 to set policy to provide for protection of the 18 environment and for workers. I think that in the 19 context of policy that standard setting is very 20 appropriate. It does not necessarily mean that 21 it's based on issues that are relevant to causation 22 and in terms of a science. 23 Q. Let's change subjects slightly. Have 24 you visited any of the plants which are the subject 25 matter of these two cases? Associated Reporters, Inc. (504) 529-3355 92 1 A. No. 2 Q. Have you got any of the plant diagrams? 3 A. I don't have any. I may have seen 4 plant diagrams in the Ellis case. I don't know if 5 we are talking about the same facility or not. 6 Q. Would it be of any use to you to go 7 through the plaintiffs' testimony in the context of 8 piping diagrams or diagrams of locations where they 9 may have worked in process plants? 10 A. Not unless I am provided with some 11 meaningful industrial hygiene data. 12 Q. Such as personal monitoring? 13 A. Something. 14 Q. Exposure levels? Do you know if that 15 information is out there at any of the plants? 16 A. No, I don't. 17 Q. Have you requested it? 18 A. I have asked for what information was 19 available on exposure. 20 Q. Have you received any type of benzene 21 monitoring information on any of the plants? 22 A. With respect to this particular case, 23 no. 24 Q. Not limiting it to personal monitoring, 25 but any type of benzene monitoring at any of the Associated Reporters, Inc. (504) 529-3355 93 1 plants at any time; do you have that information? 2 A. Levels? 3 Q. Yes. 4 A. Not to my knowledge, no. 5 Q. Do you know whether any of it exists or 6 you just don't have it? 7 A. If it exists, I don't have it. 8 Q. To your knowledge, have any industrial 9 hygiene studies been done of any of the plants 10 which are the subject matter of this case which 11 might be out in the public domain? 12 A. Not that I know of. 13 Q. From what cell does the myeloma come 14 from which would be the multiple myeloma that we 15 would have in these cases? 16 A. It's in the lymphoid lineage, and it's 17 in the B lymphocyte lineage. 18 Q. And it would originate in the bone 19 marrow; is that correct? 20 A. Yes. 21 Q. Is there a concept of biological 22 plausibility for the connection of benzene with the 23 occurrence of multiple myeloma in human beings? 24 A. I don't understand the question. 25 Q. Is there a concept called biological Associated Reporters, Inc. (504) 529-3355 94 1 plausibility for the occurrence of a disease; in 2 other words, a connection between an exposure and 3 the occurrence of a disease? 4 A. Can you define "biological 5 plausibility" for me? 6 Q. Well, I am asking you. I mean I have 7 seen that term in a couple of different contexts, 8 and the context I am talking about, is it plausible 9 for an exposure to occur and a reaction occur 10 within the body that would result in the disease? 11 And I am limiting it right now to multiple myeloma. 12 MR. McCALL: Counsel, let me object to 13 the form. I don't understand your 14 question; it's vague. 15 BY MR. FLERLAGE: 16 Q. Is there a difference between the way 17 the benzene metabolites react in the bone marrow 18 between the B-cells you have just described for the 19 multiple myeloma and the cells which are affected 20 which result in AML? 21 A. Yes. 22 Q. And how? 23 A. The benzene metabolites are known 24 metabolites, primarily, but in concert with phenol 25 and catechol, alter cytocon response in Associated Reporters, Inc. (504) 529-3355 95 1 differentiation in the myeloid progenitor 2 population. It appears that they enhance 3 recruitment of an earlier cell into the myeloid 4 lineage and increase the number of cells that are 5 at risk of replication error. 6 This is a regulatory effect, and it 7 coincides with a cell type that has the metabolic 8 machinery to produce those metabolites, namely 9 peroxidates, I think. So it is a very -- the 10 susceptibility of that population to altered 11 regulation of growth coincides with the machinery 12 to metabolize the metabolites of benzene to produce 13 the compounds that do this. 14 The lymphoid cells do not have the same 15 metabolic machinery, and coincidentally, at least 16 to date, we have not seen regulatory changes in 17 those cell types. At much higher concentrations in 18 the metabolites, several levels of magnitude 19 higher, we do see toxicity. So benzene metabolites 20 will suppress lymphoid cell function at higher 21 concentrations. 22 The altered regulation of the myeloid 23 progenitor cells, in terms of their growth and 24 differentiation, forms the basis of our theory with 25 respect to secondary leukemogenesis, and it Associated Reporters, Inc. (504) 529-3355 96 1 corresponds not only to benzene, but one also sees 2 it for a variety of chemotherapeutic drugs that are 3 also known to cause AML. 4 We are pursuing studies in lymphoid 5 populations, but we have to develop technologies 6 that don't exist at the present time in order to do 7 that. But certainly in terms of susceptibility and 8 measurable events that occur, there are differences 9 in the metabolism and the concentrations of these 10 compounds that produce changes in these different 11 cell populations. 12 Q. Is that based on an animal model that 13 you are making this distinction? 14 A. At the present time it's based on 15 studies involving the use of mouse bone marrow. We 16 are in the process now of comparing human to mouse. 17 Q. And that would be for all of the bone 18 marrow disease processes? 19 A. It would be for the types of phenomena 20 that we are talking about now in terms of 21 regulating progenitor cell function and 22 differentiation. 23 Q. Are there different benzene metabolites 24 that are created in the body as a result of the 25 ingestion or inhalation of benzene? Associated Reporters, Inc. (504) 529-3355 97 1 A. Sure. 2 Q. Do the metabolites react the same way 3 regardless of distinction in the bone marrow? 4 A. No. No, there are marked differences. 5 Some of them are toxic. Some of them alter 6 regulation or recruitment of cells in response to 7 natural hormones or cytocons. Some of them don't 8 do anything. Some of them are genotoxic; that is, 9 they will cause chromosomal aberrations or types of 10 changes that could lead to altered regulation of 11 gene expression in the cells. Some of them don't. 12 Q. Based on your mechanical model, using 13 mouse bone marrow to this point, do all the various 14 metabolites that you have investigated thus far 15 react the same way in lymphoid and myeloid cells? 16 MS. ARRAS: I am going to object to the 17 form. 18 A. If you are asking me do all the 19 metabolites do exactly the same thing in two 20 different types of cells, my answer is no. 21 Q. What I am after is, given your models 22 thus far, your animal models thus far, is it known 23 whether the benzene metabolites will affect the 24 lymphoid cells, and I am talking about the 25 alteration process that you described, in the same Associated Reporters, Inc. (504) 529-3355 98 1 sense that they will affect the myeloid cells in 2 causing AML? 3 MS. ARRAS: I am going to object to the 4 form. 5 A. I think I have answered your question, 6 if I understand. We have done over the last 15 7 years a series of studies that characterized the 8 toxicity of these cells on lymphoid populations. 9 In the last five years, we have focused 10 on looking at myeloid differentiation, because this 11 is the population that is most relevant to the 12 issue of acute myelogenous leukemia. What we have 13 found is, whereas you can produce toxicity with 14 some of the metabolites of benzene to lymphoid 15 cells, and by "toxicity," I mean stop them from 16 growing, one sees dramatic changes in the 17 regulation of function of the myeloid cells at even 18 lower concentrations. 19 Q. I don't want to interrupt you here, but 20 I want to know is whether you have determined 21 whether those metabolites will also do that in the 22 lymphoid cells. 23 A. We have no evidence to support that at 24 the present time. As I said, we are in the process 25 of studying that question, but we are having to Associated Reporters, Inc. (504) 529-3355 99 1 develop a technique to do that that doesn't exist 2 at the present time. Certainly the toxicity 3 profile is different. 4 Q. Are you prepared to give an opinion, 5 again, to a reasonable degree of scientific 6 certainty, today based on your mechanistic 7 evaluation of the lymphoid cells as to whether it's 8 just not possible for the benzene metabolites to 9 cause the myeloma? 10 A. At the present time, we do not have 11 sufficient information to draw that conclusion in 12 the way you have framed it. If I understand the 13 line of your questioning, initially you were asking 14 me are there differences between the two different 15 types of cells that would be consistent with a 16 difference in potential susceptibility, and I am 17 saying yes, there are. There are metabolic 18 differences, there are observed differences -19 which, again, metabolic differences are very 20 important. 21 There are observed differences in 22 alterations and regulation we simply haven't seen 23 in lymphoid models. We need to do further 24 development on that. And there are differences in 25 susceptibility to toxicity at higher Associated Reporters, Inc. (504) 529-3355 100 1 concentrations, so there are differences that 2 coincide with the observed association between 3 benzene exposure and AML in man. 4 Q. What I was after, though, was I guess 5 you can't give me a yes or no to that, but are you 6 able to say categorically that the benzene 7 metabolites will not affect the lymphoid cells in 8 the same sense that they affect the myeloid cells? 9 A. I can't say that categorically, no. 10 Q. This is from a report by -- I am going 11 to read a passage here, and I will show it to you 12 if you would like me to. I don't have a complete 13 copy of it, unfortunately. It's from the annals of 14 New York Academy of Science, Goldstein, "Exposure 15 to Benzene," and it talks about the relation of 16 benzene to multiple myeloma, and it talks about 17 biomedical plausibility. I don't know if you have 18 read anything by Dr. Goldstein on that or not. 19 MR. McCALL: Page 227? 20 MR. FLERLAGE: There you go. 21 BY MR. FLERLAGE: 22 Q. It's "Biomedical Plausibility." "There 23 is a high level of biomedical plausibility 24 supporting a causal relationship between benzene 25 exposure and multiple myelomas. Biological Associated Reporters, Inc. (504) 529-3355 101 1 reactive intermediates of benzene are carcinogenic 2 within the bone marrow, and plasma cells are 3 located within the bone marrow. The basic cell 4 type of plasma cells, the B lymphcyte, is affected 5 by benzene and is probably the circulating 6 lymphocytic cell found with benzene-induced 7 cytogenic abnormalities. Thus we have a carcinogen 8 that is specific to the organ at risk and affects 9 the basic cell type, including producing cytogenic 10 abnormalities." 11 I guess my question with regard to 12 that, and I think you have a copy of it in front of 13 you now, is do you agree with that statement? 14 A. I don't agree with all of it, no. I 15 think there is a basic misconception that is 16 understandable in the context of its subtlety and 17 our knowledge with respect to the ontogeny of 18 multiple myeloma. But the origin of multiple 19 myeloma appears to be a cell that resides in the 20 bone marrow and is probably -- at this point it's 21 indeterminate, but probably somewhere between the 22 level of differentiation of the pre B-cell, which 23 could be considered technically one of committed 24 stem cell population, and the B-cell. 25 So we are looking at an earlier cell as Associated Reporters, Inc. (504) 529-3355 102 1 the origin that he is referring to here in terms of 2 the circulating lymphocyte, and I think that 3 although there is no definitive pinpointing of 4 where in differentiation this occurs, there is 5 substantial evidence to suggest it's earlier than 6 this particular cell that he is talking about. 7 Q. Now Dr. Goldstein, I think -- I don't 8 have the date on this. I think it was written in 9 what, 1987? Are you aware of that? 10 A. 1990. 11 Q. 1990? Based on what you have 12 discovered I guess since 1990, are you aware of any 13 retraction of this by Dr. Goldstein? 14 A. No. And I don't think that that's an 15 accurate representation. Some of the literature to 16 support what I have just said existed prior to 17 1990, but it's certainly been developing over the 18 last several years. I am simply saying that with 19 respect to this one statement that he made, he is 20 not taking into account the evidence to suggest 21 that the cell of origin for multiple myeloma occurs 22 earlier in ontogeny than he is describing here. I 23 think he is basically misstating. 24 Q. It's Dr. Goldstein's position, I 25 understand, that he has related exposure to benzene Associated Reporters, Inc. (504) 529-3355 103 1 to multiple myeloma; is that correct, based upon 2 both the biomedical plausibility and the human 3 findings? 4 MS. ARRAS: I am going to object to the 5 form of the question. You are asking 6 Dr. Irons to draw a conclusion about an 7 entire study, which you haven't laid 8 the foundation for whether he is 9 familiar with it, whether he has read 10 it, and therefore whether he can draw 11 a conclusion as to what Dr. Goldstein's 12 ultimate conclusion was. 13 MR. FLERLAGE: Well, he has got it 14 right in front of him. I guess in 15 answering the question, he can do 16 whatever he wants with it. 17 MS. ARRAS: Well, can he read it? 18 MR. FLERLAGE: Sure. 19 THE WITNESS: Well, I am going to have 20 to take a more detailed look at this to 21 answer that question. 22 (OFF THE RECORD DISCUSSION) 23 BY MR. FLERLAGE: 24 Q. To the best of your knowledge, has 25 Dr. Goldstein linked occupational exposure to Associated Reporters, Inc. (504) 529-3355 104 1 benzene with multiple myeloma? 2 A. Well, I think in his concluding 3 paragraph in this particular review -- which is 4 again a review; it's an opinion, not a primary 5 research article -- "Overall, these findings are 6 not sufficient to make an unequivocal statement 7 that benzene is a cause of multiple myeloma. 8 However, they raise the strong presumption of such 9 a causal link, and in my judgment, it is now more 10 likely than not that benzene exposure is an 11 etiological factor in multiple myeloma. This does 12 not necessarily mean that any increase in the 13 incidence of multiple myeloma in recent years can 14 necessarily be ascribed to benzene use, but it does 15 raise an issue that needs to be considered." 16 That's his opinion. In terms of the 17 issues that he has raised with respect to the 18 epidemiology and the biology, I think there are 19 aspects that I would agree with. 20 There are aspects that I don't agree 21 with. I would say that we disagree with respect to 22 the presumption, and in fact I think that the data 23 does not support that conclusion. We obviously 24 have a difference of opinion with respect to the 25 weight of the evidence at this point. We disagree Associated Reporters, Inc. (504) 529-3355 105 1 on many things and agree on many things. This 2 doesn't strike me as anything that -3 Q. Do you understand the standard in a 4 civil litigation matter such as this to give an 5 opinion as more likely than not? 6 A. Yes. 7 Q. Is that the same standard that you 8 would use as a scientist in ariving at an opinion? 9 A. If I am evaluating a variety of 10 different studies or a body of literature to reach 11 a conclusion, yes. If I am looking at an 12 individual study to determine whether it is a 13 reliable indicator or I can draw a reasonable 14 conclusion, I will use a 95 percent confidence 15 interval or a higher standard. That is evaluating 16 the validity and the scientific rigor in an 17 individual study. But for looking at the 18 literature as a whole, I'm applying a more probable 19 than not, greater than 50 percent standard. 20 Q. Is that greater than 50 percent 21 standard the standard that you have applied in 22 giving your opinion that exposure to benzene does 23 not cause multiple myeloma? 24 A. With the caveat that I have evaluated 25 the strength, design, validity of the conclusions Associated Reporters, Inc. (504) 529-3355 106 1 and findings reached in the individual papers in 2 reaching that conclusion, yes. 3 Q. Okay. Would it then be fair to say 4 that it's your opinion that it's not biologically 5 plausible that benzene will affect the bone marrow 6 to such an extent that it can result in a multiple 7 myeloma? 8 A. There is no evidence that will allow me 9 to say it is not biologically plausible. However, 10 there is considerable evidence to suggest -- I have 11 got this backwards. 12 It is impossible to conclude that it is 13 plausible with any kind of definition. There is 14 considerable indirect evidence to suggest that it 15 may not be, but the state of the art is such that I 16 cannot definitively reach a conclusion as to its 17 plausibility or lack thereof. 18 Q. Okay. At this point I am going to have 19 to take a look at the materials. 20 (A NOON RECESS WAS TAKEN) 21 BY MR. FLERLAGE: 22 Q. Doctor, in the last hour, maybe half an 23 hour, 45 minutes or something like that, I've been 24 going through some of the materials that you have 25 provided which are going to be in Exhibit No. 5, I Associated Reporters, Inc. (504) 529-3355 107 1 think it is, to the deposition. There is a number 2 of epidemiological studies which are in the first 3 section that you have identified as being 4 supportive of your position; is that correct? 5 A. Yes. 6 Q. Can you answer for me how you went 7 about synthesizing, if you will, materials in those 8 reports to form an opinion? 9 A. Well, I classified them in terms of the 10 type of report or study that they were. I then 11 went through and evaluated them with respect to 12 study population, experimental design, what 13 criteria were used for classification of exposure 14 or measurement of exposure, what types of 15 comparisons were made, whether they were controlled 16 versus general population, proportion mortality or 17 retrospective cohort, case-control studies. 18 I then went through in my own mind and 19 on paper and began to summarize those findings from 20 one study to another and looked at the pattern of 21 results that were seen from one study to another. 22 Q. Some of the studies in there find a 23 causal connection between exposure to benzene in an 24 occupational setting and multiple myeloma; do they 25 not? Associated Reporters, Inc. (504) 529-3355 108 1 A. If you take an individual study, for 2 instance, if you take the Rinsky study, the initial 3 study saw no relationship. The followup suggested 4 there was a relationship. If you take an 5 individual study like that, you can say yes, that 6 that was the conclusion of the authors of that 7 study, but I think when you look at the design of 8 that study, the classifications and their use of 9 the information that they had, as well as in the 10 context of all the other studies that I have looked 11 at, that that's really the exception to the rule. 12 Q. Okay. In looking at the studies 13 individually as you have described, are there any 14 studies that you would care to address as having 15 more weight in terms of your opinion? 16 A. Yes. You have to look at the size of 17 the study, its power to see a change, you have to 18 look at the design of the study and what 19 assumptions are made by the individual 20 investigators in conducting the study and in 21 reaching their conclusions. 22 If you do that, I think that one can 23 make some distinctions with respect to the 24 reliability of the conclusions that have been 25 reached. I don't think it's -- I mean I can do Associated Reporters, Inc. (504) 529-3355 109 1 that as an exercise. I don't think that in general 2 it's as critical as it might be in some cases, 3 because I think the predominant finding and the 4 results, taking literature as a whole, support the 5 position that there is no demonstrable relationship 6 between benzene exposure and multiple myeloma. 7 Q. Which are the studies you were 8 referring to that make the causal connection 9 between farming or ranching and multiple myeloma? 10 A. For the most part, that comes from 11 population-based case-control studies in which 12 farming has been seen as being a risk factor. 13 There are case-control studies that are related 14 specifically to multiple myeloma. 15 In terms of lymphoma, there are also 16 some that have looked at farming as an occupation 17 that suggests a relationship there as well that are 18 probably larger than some of these, and it's my 19 understanding the results of a recent study that 20 has been sponsored by NCI that draws the same 21 conclusion that has yet not been published. 22 Q. Are you familiar with the statistics 23 and the analysis of that study? 24 A. No. 25 Q. How are you aware of the report? Associated Reporters, Inc. (504) 529-3355 110 1 A. I have read about it. It's been 2 bantered around in the popular press, but I have 3 not yet seen it in the scientific literature. 4 To speak specifically to your question, 5 the Morris study from 1986 saw an association with 6 the exposure to fertilizers. The Flodin study, 7 which is Swedish, found a relationship or at least 8 described a relationship for farming as far as 9 multiple myeloma. The McLaughlin study from 1988 10 found at least as high, if not higher, association 11 between farming and say petroleum industry. 12 Q. There was another one that was in there 13 that was Cuzick or something like that that you had 14 in there? 15 A. Cuzick, also Eriksson. The Cuzick 16 study, it's hard to draw any quantitative 17 conclusions from. The conclusions of the author 18 are that there is at least a two-fold risk 19 associated with farming and food processing, and 20 perhaps a risk associated with asbestos exposure. 21 There is no way that I could put a quantitative 22 value on this. 23 Q. They also found the petrochemical 24 industry to be a potential causative factor, did 25 they not? Associated Reporters, Inc. (504) 529-3355 111 1 A. I believe that is mentioned in there as 2 well. 3 Q. With at least some of these studies 4 which we are isolating with regard to farming or 5 ranching or animal exposure, there is at least an 6 underlying theme in many of the studies that 7 exposure to petroleum products or chemical products 8 is also implicated as a causal factor; is that 9 correct? 10 A. As I mentioned before, the farming 11 industry represents a very complex exposure 12 scenario, and there is probably as much of a theme, 13 if not greater theme, with respect to the 14 hypothesis that we are looking at, antigen 15 stimulation, potential exposure to viruses, and a 16 variety of other confounders as well. 17 At this point in time, I don't know how 18 you would go about segregating those out, but it's 19 clear that farming shows up repeatedly. I mean the 20 strength of the association varies from study to 21 study, and you will see that. That's one of the 22 reasons why I think you have to look across the 23 board at the whole literature as opposed to any one 24 individual study. 25 I don't think there is an individual Associated Reporters, Inc. (504) 529-3355 112 1 study that I can think of in this whole arena that 2 in and of itself provides you with a definitive -3 at least with me, with sufficient evidence to say 4 yes, this is a causal relationship. You have to 5 look at the pattern that exists, and the pattern 6 with respect to farming is clear. 7 Q. Is there also a pattern, or is there 8 not a pattern concerning exposure to chemicals and 9 petrochemicals also, which is an underlying theme 10 through most of the studies that you are talking 11 about? 12 A. No. I think the pattern is entirely -13 if there is a pattern at all, it does not 14 support -- it's not consistent and it doesn't 15 support a conclusion that there is an increased 16 risk. We have varying degrees of association with 17 chemical exposure, some of them related to 18 aromatics, some to solvents, some to chemicals. 19 Some distinguish between benzene, some don't. 20 But if you look across the board, I 21 mean we have odds ratios and relative risks that do 22 not provide and don't certainly suggest to me that 23 there is a consistent pattern of increase. Some of 24 these, there is actually a significant deficit. 25 There is no association that can be drawn. Associated Reporters, Inc. (504) 529-3355 113 1 Q. Is there any explanation for finding a 2 deficit in terms of disease occurrence among 3 potentially exposed populations? 4 A. Well, in some cases, occasionally 5 someone will hypothesize that a deficit in an 6 epidemiologic study or a non-dose-response 7 relationship may be in fact due to some what I 8 would consider to be biologically unlikely 9 explanation, but usually I think it's a function of 10 the artifact of the process of the types of studies 11 that we are talking about, epidemiology. 12 For instance, if you have an excess of 13 a disease in a population that you are not studying 14 or that you may be discounting, it may ask skew the 15 potential findings relative to the general 16 population or to some control. That definitely 17 happens in proportional mortality studies, which 18 are very unreliable for that reason, but it can 19 also happen in a retrospective cohort study or a 20 case-control study if it's not recognized and 21 controlled for during the design phase of the 22 study. 23 Q. Doctor, did you testify or were you 24 invited to testify before OSHA promulgated rules 25 concerning benzene exposure? Associated Reporters, Inc. (504) 529-3355 114 1 A. The only testimony I have made before a 2 regulatory hearing was in '80 or '81, and it was an 3 OSHA hearing on benzene emissions from a lake and 4 hydride plant. I have not participated in any of 5 the regulatory hearings on benzene per se. 6 Q. Are you familiar with the OSHA 7 regulations concerning benzene? 8 A. Generally, yes. 9 Q. Have you reviewed them recently? 10 A. Specifically, probably not. 11 Q. Okay. 12 A. I can't recall. 13 Q. Are you aware of OSHA's opinion forming 14 the basis of some of its regulation with regard to 15 benzene, concerning benzene and its relationship to 16 multiple myeloma? 17 MS. ARRAS: I am going to object to the 18 form of the question. I don't know 19 that OSHA can have an opinion in the 20 sense that you are implying here. If 21 you can answer the question -22 A. She stole my answer. I don't know what 23 you mean by an opinion of OSHA. OSHA sets 24 standards. 25 Q. Are you familiar with the background Associated Reporters, Inc. (504) 529-3355 115 1 for the standards that went into the rationale for 2 standards in terms of benzene? 3 A. I am familiar with the benzene 4 literature which forms the basis for rule-making. 5 Q. Isn't it a fact that OSHA took the same 6 literature that you are referring to in your 7 Exhibit No. 5 and came to a different conclusion 8 with regard to benzene and multiple myeloma? 9 MS. ARRAS: I am going to object to the 10 form. 11 A. OSHA does not -- OSHA sets standards. 12 It does not classify agents as carcinogenic or not. 13 It promulgates rules with respect to exposure. 14 Individuals who work for OSHA I am sure reach 15 conclusions that form the basis for that 16 rule-making, but again, OSHA is not an agency that 17 to my knowledge renders opinions, but rather sets 18 standards with respect to worker safety. 19 Q. Would it be fair to say then that they 20 are very opinionated about their standards? 21 MS. ARRAS: I am going to object to the 22 form. 23 MR. McCALL: I will object to the form 24 also, as it calls for speculation. 25 MR. FLERLAGE: I will withdraw the Associated Reporters, Inc. (504) 529-3355 116 1 question. At least Dr. Wong would have 2 appreciated that. 3 BY MR. FLERLAGE: 4 Q. I went through this with Dr. Wong, and 5 I don't know if you are familiar with this whole 6 thing or not, but this is the 29 CFR, Part 1910, 7 Department of Labor, Occupational Safety and Health 8 Administration, Friday, September 11, 1987. The 9 part I have underlined is what I went through. 10 MS. ARRAS: Specifically what page? 11 34,479? 12 BY MR. FLERLAGE: 13 Q. Yes. With regard to that underlined 14 section, do you agree with or disagree with the 15 conclusion with regard to multiple myeloma and 16 benzene? 17 A. I disagree with the conclusion. By the 18 same token, this is not a scientific document. 19 This is a statement made in the Federal Register in 20 support of a rule-making in which OSHA is clearly 21 faced with providing appropriate cost benefit 22 analysis. It's a legal regulatory issue. I don't 23 think that it really speaks to the scientific 24 issue. 25 Q. I suppose I ought to read it into the Associated Reporters, Inc. (504) 529-3355 117 1 record again. The passage we were referring to 2 was, again, from Page 34,479. 3 "Epidemiologic studies demonstrate that 4 benzene exposure can cause leukemia, multiple 5 myeloma, and perhaps other hematopoietic and 6 lymphatic cancers. Aplastic anemia and several 7 other blood diseases are also known to be caused by 8 benzene exposure. Observations related to the 9 above findings have been demonstrated by a number 10 of high quality epidemiologic studies and case 11 reports, such as those by Rinsky, Wong, Ott, 12 Decoufle, Infante, Aksoy, Vigliani and others." 13 That's the passage we were referring 14 to. Whether you want to talk about it being 15 authoritative or not, you disagree with that 16 conclusion; is that correct, Doctor? 17 A. I disagree with some of those 18 conclusions; by no means all of them. 19 MS. ARRAS: You're not going to read 20 the rest of that paragraph into the 21 record? 22 MR. FLERLAGE: No. I don't think I did 23 yesterday. No, not unless you want to. 24 BY MR. FLERLAGE: 25 Q. Mr. Stelly was a pipefitter, correct? Associated Reporters, Inc. (504) 529-3355 118 1 A. Yes. 2 Q. We went through this to a limited 3 extent, but is there any way you can characterize 4 whether he engaged in the repair or maintenance of 5 any chemical reactors, valves, fittings or pipes? 6 A. To the best of my recollection, he 7 describes repairing pipes. 8 Q. And not specific fittings or anything, 9 valves, process piping, anything like that? 10 A. At this point, not that I recall. 11 Q. Did either Mr. Stelly or Mr. LeBlanc 12 talk about safety precautions which they may have 13 been offered or took in any of the plants we're 14 involved with? 15 A. I recall some statements to that 16 effect. 17 Q. Which were they? 18 A. I would have to refer back to the 19 deposition to be accurate, but I do recall some 20 discussion of that. 21 Q. Did that enter into your opinion-making 22 in this case at all, whether or not they wore 23 safety devices or took precautions? 24 A. The issue of exposure and dose is not 25 relevant to the question of causation in my Associated Reporters, Inc. (504) 529-3355 119 1 opinion. From that standpoint, I did not require 2 in reaching my opinion to have an abject knowledge 3 of their specific exposure, because I don't think 4 it's relevant. 5 As I mentioned before, there is nothing 6 within the information I have read that would allow 7 me to assess any exposure, but by the same token, 8 it's not significant with respect to my opinion of 9 causation between benzene and multiple myeloma. 10 Q. Did you need either one of these 11 gentlemen's occupational exposure backgrounds to 12 form a opinion in this case? 13 A. To the extent that it provides the 14 basis for understanding what the allegations are, 15 yes, but in terms of reaching an opinion on 16 causation and what the literature says with respect 17 to causation, no. 18 Q. Would it be fair to say that given the 19 disease process, multiple myeloma, it doesn't 20 matter how much exposure to benzene either one of 21 these gentlemen may have had, in your opinion? 22 A. Based upon the literature today, that's 23 correct. The actual exposure is not at issue here. 24 That's not the issue in multiple myeloma. 25 Q. Doctor, I think I only have one other Associated Reporters, Inc. (504) 529-3355 120 1 area. In the Ellis deposition on December 17, 2 1991, on Page 55, and let me read it into the 3 record and then I will give it to you, you were 4 asked the following question on Page 55, Line 18. 5 "Do you believe there is more evidence 6 that benzene causes multiple myeloma than the 7 lymphoid leukemias?" 8 And your answer at Line 21 was "I would 9 say yes, but I would also like to explain. I don't 10 think there is sufficient evidence to indicate that 11 benzene causes multiple myeloma, so we are talking 12 about grades of insufficient evidence. I believe 13 there is no evidence that benzene is associated 14 with lymphoid leukemias." Let me show you that to 15 make sure I read it right. 16 A. Okay. I recall that. 17 Q. Is that still your testimony today, 18 or has that changed? 19 A. I would say that, in general, 20 my testimony is consistent with this, to the 21 extent that I have strengthened my opinion with 22 respect to the lack of evidence for multiple 23 myeloma, following my reading of the literature 24 that currently exists. 25 At the point in time that I said Associated Reporters, Inc. (504) 529-3355 121 1 this, I was referring specifically to the 2 Tabershaw-Cooper study and to the Rinsky study 3 as being the basis for this statement. 4 As I mentioned earlier, at the request 5 of Ms. Arras, I reviewed all the literature that we 6 have here, and I think that it strengthens my 7 conclusion that there is no evidence that would 8 support the conclusion that multiple myeloma is 9 associated with benzene. 10 But by the same token, again, if we are 11 going to talk about grades of insufficiency, I 12 think that this statement still is true. 13 Q. Okay. I have no further questions. 14 Thank you. 15 MR. FLERLAGE: Read and sign? 16 MS. ARRAS: Yes. 17 18 19 (DEPOSITION CONCLUDED) 20 21 22 23 24 25 Associated Reporters, Inc. (504) 529-3355 122 1 2 CERTIFICATE 3 4 I, JULIE L. SAMFORD, Certified 5 Shorthand Reporter, do hereby certify that the 6 witness, after having been first duly sworn to 7 testify to the truth, the whole truth, and nothing 8 but the truth, did testify as hereinabove set 9 forth; 10 11 That the testimony was reported by me in 12 shorthand and transcribed under my personal 13 direction and supervision, and is a true and 14 correct transcript, to the best of my ability and 15 understanding; 16 17 That I am not of counsel, not related to 18 counsel or the parties hereto, and have no personal 19 interest in the outcome of this event. 20 21 22 23 _____________________________ JULIE L. SAMFORD 24 Certified Shorthand Reporter 25 Associated Reporters, Inc. (504) 529-3355