Document Ev87E5dB5VyxqERYzRL2GjkOL

KECEIVEQ IN THE UNITED STATES DISTRICT COURT *^^2 7/982 FOR THE EASTON DISTRICT OF PENNSYLVANIA ^USlQfcS I THOMAS J. MCCONNELL and DIANE : CIVIL ACTION j McCONNELL, his wife, individually: ! and on their own behalf and as : ! parents and natural guardians of : 1 KRISTINE McCONNELLL, a minor, : vs. CIBA-GEIGY CORPORATION and * j : ORKIN EXTERMINATING COMPANY, INC.: NO.80-1692 Philadelphia, Pennsylvania December 9, 10, 1962 ji BEFORE: HON. ALFRED L. LUONGO, CHIEF JUDGE (And a Jury) TESTIMONY OF DR. SAMUEL EPSTEIN APPEARANCES: STEPHEN R. BOLDEN, ESQ., WILLIAM W. SPALDING, ESQ., RICHARD C. FERRON1, ESQ., Attorneys for the Plaintiffs F. HASTINGS GRIFFIN, JR., ESQ., FRANK J. EISENHART, JR., ESQ., Attorneys for Ciba-Geigy EDWARD L. McCANDLESS, ESQ., Attorney for Orkin 20924001 REPORTED BY i DAVID S. EHRLICH, CSR, RPR, CP, CM OFFICIAL COURT REPORTERS Room 2722 U.S. Courthouse Philadelphia Pa. 19106 BFG08014 1 DR. SAMUEL EPSTEIN, Sworn. 2 TEE COURT REPORTER: State your full name, 3 please. 4 THE WITNESS: Samuel Epstein, E-p-s-t-e-i* 5 DIRECT EXAMINATION a BY MR. BOLDEN: 7 Q. What is your profession. Doctor? 8A I am a toxicologist, pathologist, M.D.. 9 0- Do you specialize in any areas of medicine? 10 A I specialize in the effects of toxic chemicals in 11 the environment, in air, water, food and the workplace. 12 Q. Would you give us your educational background. 13 A My educational background# as spelled out in 14 the curriculum which I gave you, is basically that of, 15 I qualified in physiology in London University, England, 18 I took a degree in medicine in 1950 in Gy's Hospital 17 in London University; in 1952 I took a degree in 18 tropical medicine and hygiene; in 1954 I took a degree 19 in pathology; in 1958 I took an advanced degree in 20 medicine; in 1963 I was awarded a Diplomats in public 21 health and medical laboratory microbiology; in 1971 I 22 was a Fellow of the World Society of Health, in England. 23 Q. By whom are you employed at the present time? 24 A University of Illinois Medical Center. 25 Cl And, in what position are you employed by them? z o o tz e o z BFG08015 3 Dr. Epstein - Direct t A. I an Professor of Occupational and Environmental 2 Medicine. 3 ft 4 A. What does that mean? That means basically that I have the responsibiliti s 5 in the areas of occupational health and environmental 6 health, with particular reference to considering, 7 discussing, researching problems of toxic chemicals, 8 either in the workplace or in the general environment, 9 and in consumer products too. 10 & How long have you been associated with the 11 University? 12 A. Since about 1976. 13 Ql Save you ever acted as a consultant to any federal 14 or state agencies in the areas in which you specialize? 15 A. Oh, very, very, very much so. 16 Ql Would you please list them for us, what you have 17 done 18 A. First of all, I was a consultant -- I have been 19 a consultant to Congress for many years. From *69 20 onwards, 1 was a consultant to the Senate Committee on 21 Public Works, and assisted them in their analysis of 22 problems of adverse health effects from air pollution 23 and from water pollution, with particular'reference to 24 toxic chemicals. 25 I have consulted to other congressional BFG08016 4 Dr. Epstein - Direct 1 committees on and off since then, most recently to 2 Veterans' committees on problems of Vietnam Veterans 3 and Agent Orange. 4 Additionally, I have acted as an expert 5 witness in the Environmental Protection Agency in a 6 variety of its Cancellation-Suspension proceedings 7 against pesticides, with particular reference to aldrin, 8 dieldrin and chlordane, and heptachlor. 9 I have consulted to the Occupational 10 Safety and Sealth Administration extensively, and in 11 fact was in 1973, one, a member of a small committee 12 that set up the first guidelines for regulation of 13 occupational carcinogens, cancer-causing chemicals in 14 the workplace. 15 Additionally, I have been a consultant 16 I have been a member of expert committees for the 17 Environmental Protection Agency, particularly the 18 Environmental Health Advisory Committee, and pesticide 19 subcommittees which had specific reference and expertise 20 in areas of pesticide regulation, and have helped to 21 develop guidelines for methods of testing for pesticides, 22 and also for problems of pesticide exposures. 23 Additionally, I was the Chairman of the 24 Teratology Committee, the Teratological Panel -- that is 25 the birth defects panel -- of a major government BFG08017 5 Or. Epstein - Direct 1 commission in 1969. 2 Secretary Finch, in 1969, who was HEW's 3 Secretary, convened a panel, a commission, known as 4 the MRAK Commission, specifically to investigate problemfe 5 of pesticides and their relationship to environmental 6 health. And, I sat on the Carcinogen Committee, that 7 is the cancer -- problems of cancer from pesticides. B I was the Chairman of the Mutagenicity Committee -- that 9 is the committee on genetic effects, adverse genetic 10 effects of pesticides; and. Chairman of the Teratology 11 Panel or Committee. 12 Additionally, I have acted as consultant 13 to various state boards. 1 was consultant to the 14 Massachusetts Pesticide Board from 1970 to 1971; and 15 additionally, I have consulted to Governor Brown in 16 California on various aspects of toxic chemicals, IT including pesticides. 18 That is, X think, as far as I can recall $ 19 those are the major areas of my involvement with 20 government in problems of pesticides. 21 0 Are you a member of any professional organization 22 which deal in your area? 23 A. Yes. The professional organizations which X have 24 been involved in, on page 3 -- and, there are about 25 thirteen professional societies and organizations. BFG08018 6 Dr. Epstein * Direct ranging from New York Academy of Sciences, Society of Occupational Environmental Health, which was the society composed of government, management, academia and labor, and I was the president of that society; The American Association for the Advance ment of Science; The Environmental Mutagen Society, of which I was a co-founder and executive secretary; The Society of Toxicology; largely an industry oriented society of professional toxicologists, although with membership from academia and government; and this society gave me the Honors Achievement Award in about 1970; American Board of Microbiology, American Association for Cancer Research, American Society for Experimental Pathology, Air Pollution Control Administra tion, Society of Protozoologists, Society for General Microbiology, and Society for Pathology and Bacteriology, fit Doctor -- THE COURT: Excuse me. Do you wish to question on qualifications? Had you concluded on qualifications? MR. BOLDEN: I was going to get into some of the articles he was involved in, if I might, your Honor. THE COURT: Sorry. Go ahead. BFG08019 7 < Dr. Epstein - Direct 1 BY MR. BOLDEN: 2 Ql Have you published articles or texts in your field, ( 3 and specifically any in the area of teratology? 4 A. My publications amount to about 260 scientific 5 articles and about six or seven books* specifically * 6 with relation to -- I wonder if I may break down your 7 question into more manageable elements. < I have about 30 publications on pesticides* and as far as publications on reproductive 10 toxicity, including teratology* about 20 publications, < 11 including chapters in books on teratology* and also 12 publications in the official journal of teratologists 13 known as* "Teratology." So* I have reasonable publica 14 tions in the area of reproductive toxicity. rM 'Miwf. u . #* r 16 Q. One final question. Have you ever donated any of < 16 your services in an unpaid capacity in your area? I 17 A. X would say I donate a very substantial amount of 15 my time for what is called pro bono work* doing things 19 for nothing. 20 For instance, hardly a week goes by in 21 which X don't either respond to requests by radio* 22 press* TV* for information either on a consulting 23 basis or making statements. I donate my expertise ( 24 freely to citizen groups* public interest groups all 25 over the country. t BFG08020 8 Or. Epstein - Direct 1 I am the President of the Rachel Carson 2 Trust, for which I -- for several years I have never 3 been paid a penny, and lucky ever to get travel expenses. 4 For instance, I am talking about media, S this week I have three TV -- two TV appearances, Z think 6 -- one of them on pesticides in fact, and so on and 7 so forth. a Additionally, I have donated my services 9 pro bono for the last two years or so to litigation on 10 behalf of Vietnam Veterans, the Agent Orange Litigation. 11 So, I spend a great.deal of time on 12 a pro bono basis. 13 MR. BOLDEN: Your Honor, that would 14 conclude the questioning on qualifications. 15 MR. GRIFFIN: I do have a few questions, 16 your Honor. 17 THE COURT: You may. 18 VOIR DIRE EXAMINATION 19 BY MR. GRIFFIN: 20 Q, Bottom line, Doctor, are you attempting in this 21 case to qualify yourself as an expert teratologist? 22 A. No. 23 MR. GRIFFIN: In that case, your Honor, 24 I have no further questions. 25 MR. McCANDLESS: I have one or two. BFG08021 9 Dr. Epstein - Voir Dire 1 VOIR DIRE EXAMINATION 2 BY MR. McCANDLESS; 3 Qi Doctor, in what states are you licensed to practice 4 medicine? 5A None. 6 Q. You havean M.D. degree, right? 7A a Ql I do. You talked about anumber of appointments you have 9 had in consulting work. I haven't heard any date since 10 1971. Are you currently serving in any governmental 11 consulting capacity now? 12 A No. The last governmental work 1 did was, I think 13 I stopped in 1979. That was the Environmental Protection 14 Agency, the Environmental Advisory Committee. Since 15 then I have also been doing some government work on 16 a state level, particularly in California. 17 Q. Just to make it clear, is your appearance here 18 today one of your pro bono activities? 19 A No. 20 Ql 21 A 22 Ql 23 24 2S This you will be paid for? Certainly. Okay. MR. McCANDLESS: I have nothing else. THE COURT: You may proceed. MR. GRIFFIN: Your Honor, I object to 6 U 0 fr2 6 0 g BFG08022 * 10 Or. Epstein - Voir Dire 1 this Doctor who is not licensed to practice and who 2 says he is not an expert in this field that we are 3 dealing with. 4 THE COURT: I will see counsel at side S bar, because I have no idea what is intended to be 6 presented. 7 (Side bar discussion on the record as 8 follows:) 9 THE COURT: What is going to be presentee 10 HR. BOLDEN: For the purpose of 11 establishing the teratogenicity of Diazinon, and his 12 conclusions as to whether or not it was a factor in 13 causing the birth defect of Khristine McConnell. 14 THE COURT: What was your -- IS MR. GRIFFIN: My objection, sir, is 16 that the science of teratology, whether certain sub 17 stances cause teratological effects -- 18 THE COURT: I must confess I am 19 thoroughly confused. He doesn't purport himself to be 20 an expert in this field. I don't know what he is an 21 expert in. I am trying to figure it out based on 22 listening to all he has done. 23 MR. BOLDEN: I believe, your Honor, the 24 gist of what I heard, he is a toxicologist who has a 2S great deal of expertise in the area of teratology and BFG08023 11 Dr. Epstein - Direct/Side Bar i 1 pesticides -- 2 THE COURT: But, he doesn't even say C 3 that he is. He doesn't say that he is an expert 4 teratologist. That is what confused me. I was expectirg 6 him to answer Mr. Griffin's question, yes, I do. He e 6 says, no, I am not. 7 MR. GRIFFIN: He has sworn too often 8 in other cases not to be able to answer that question 9 other than no. 10 THE COURT: Well, what is it you are C 11 proposing to establish through him? 12 MR. BOLDEN: To establish that the 13 teratogenicity of this substance, and it is a factor 14 in causing birth defect. I think the argument -- 15 THE COURT: His testimony creates a 1 16 serious problem for me. I am supposed to determine 3 5 17 initially whether a person is an expert in a particular 4 18 field. If the person himself disclaims expertise. i then how can I tell the jury that I consider him an 1 20 expert even though he doesn't? MR. BOLDEN: Your Honor, I think -- sM * 22 I am not sure there even is, and I don't believe there 23 is, any such thing as a Board Certified teratologist. j ij 24 THE COURT: No, I don't think that is j 25 the question at all. The question is whether this ' Lt 1 IJ, #1^ ' IIM NUM ^ 20924011 BFG08024 12 Dr. Epstein - Direct/Side Bar 1 witness in response to a question that was posed to 2 him, is at least obligated to say, yes, I do believe 3 that I am an expert, and then he can explain there is 4 no Board certification in this sort of thing, but I am 5 qualified. He says, no. That is my problem. 8 If he himself does not purport to be an 7 expert, how can I say to the jury, "You may consider 8 him as expert in this field"? 9 Now, you may, at least assess his 10 qualifications. It creates a very serious problem. 11 Now, I see an argument can be made 12 that notwithstanding he doesn't claim to be, this jury 13 can nevertheless determine that he is. That is diffi 14 cult, because we are in an area, a very scientific area, 15 and if the witness himself doesn't even claim to be, 16 how can I let the lay persons in the jury come to the 17 conclusion that in fact he is? This is my problem, 18 and it is created by his own answer. 19 MR. BOLDEN: Well, perhaps if your Honor 20 will let me explore with him a little further the degree 21 of expert -- the degree of -- 22 THE COURT: 1 will tell you what we will 23 do. He apparently -- and, I don't know, he has not 24 been asked the question yet -- he says he is a toxicolo 25 gist. If he is going to testify simply to toxicity, I BFG08025 13 Or. Epstein - Direct/Side Bar 1 think as long as he will at least answer that question 2 that he considers himself an expert in toxicity, then f 3 maybe we will hear some testimony as to the toxicity 4 of the material. But, before you get into an area as 5 to the teratogenic effect, then we will have to considei * 6 again, because at the moment I can't permit him to 7 testify in that area. S MR. BOLDEN: Your Honor -- g MR. FERRONI: Can we question him as 10 to his dealings in the area of toxicology so as to < 11 establish a foundation or a basis for the jury -- Ml NW n 'M fHH 12 THE COURT: I have just said that -- if 13 he will simply answer that he considers himself an 14 expert in toxicology, I will permit him to testify as 15 to the qualities of these various materials. But, I 4 16 will not as this moment authorize any questions as to 17 the teratogenic effect. That's all. 18 MR. GRIFFIN: If your Honor please, 19 isn't that putting the cart before the horse? Even if 20 we spend a lot of time, and we will take a lot of 21 time with him -- 22 THE COURT: Wait a minute. Two people 4 23 are talking at once. That is no good. 24 MR. GRIFFIN: And, it will take a lot 25 of time with him because he is, in my view, as bad as i P T i fcf,-y?ivy BFG08026 14 Dr. Epstein Direct/Side Bar 1 Todd, or worse, we end up -- - 2 MR. SPALDING: I object. 3 MR. BOLDEN: He made remarks all week -- 4 MR. GRIFFIN: We end up with the ball 5 nowhere, unless they will follow it up with an opinion 6 from someone who is qualified that this particular 7 substance is teratogenic. 8 THE COURT: And, if they don't, it won't 9 get to the jury. 10 MR. GRIFFIN: I think I am entitled to 11 an offer as to whether they are going to prove that. 12 MR. BOLDEN: Let me shorten this. If 13 the Court will not accept Dr. Epstein as a person who 14 it will permit to testify with respect to teratogenicity IB of this substance, and its causal relationship to the 16 issue in this case, we have no other witness to present. 17 The only other thing I can ask the Court 18 to grant me leeway to do is to further explore with him 19 the amount of time -- because, he covered it, but. we 20 covered it hurriedly -- the amount of time he has 21 devoted to teratology and determining teratogenicity 22 of substances, and perhaps it is a question of weight, 23 rather than the -- 24 THE COURT: I have devoted a great deal 25 of my time to watching football games, that doesn't make BFG08027 15 Dr. Epstein - Direct/Side Bar 1 me an expert football player.- 2 Now, this man, if he had simply said 3 yes, I consider myself an expert, I would have permittee 4 this to proceed. But, when he himself disclaims S expertise, then I can't permit the jury to hear what 6 this man has to say; not in this area. And, this is 7 very critical in this case. a MR. BOLDEN: Well then, we have no -- 9 MR. SPALDING: I think you indicated -- 10 MR. PERRON!: Is there any question the 11 witness understood the question that was asked of him? 12 THE COURT: X doubt there was any 13 question about it. He seems to be a very, very capable 14 person and would not have answered a question if he IS had not understood it. 16 MR. McCANDLESS: It was a three-word 17 question I think it was very clear. 18 I join in Mr. Griffin's objection to 19 this. 20 MR. BOLDEN: He has used the word to 21 me, bench teratoloqist; I am not a bench teratologist. 22 I don't know what he means by that. He 23 may have been answering Mr. Griffin's question in a 24 context which is not the same as whether he considers 25 himself to have expertise in the area. BFG08028 16 f 1 Dr. Epstein - Direct /Side Bar MR. GRIFFIN: Mr. Bolden, I have sworn 2 testimony ffom him in another case in which he says, f 3 I am not a teratologist,t I cannot give a professional 4 opinion in that area, I do not consider myself qualified \ 5 in this area. * 6 THE COURT: We will cut this short. 7 Mr. Griffin has raised the question after his crossC 8 examination. You have not yet undertaken your redirect 9 examination. Do you want to ask him that direct 10 question: Do you consider yourself an expert teratolo < 11 gist in any sense; then we will find out where we go 12 from there. Then, of course, Mr. Griffin will still 13 have an opportunity to cross-examine, recross after 14 that, if he should change his answer. Just so there 15 is no question that he understood what he was being C 16 asked. 17 MR. BOLDEN: All right. 18 THE COURT: But, I caution you that if 19 that is what we end up with, that he disclaims expertise:, 20 if that is the end of the case, that is the end of the 21 case. 22 23 l 24 MR. BOLDEN: All right. (End of side bar discussion.) (* im m u 25 1 BFG08029 18 Dr. Epstein - Direct < 1 consider yourself an expert in any aspect of that 2 field? f 3 THE WITNESS: Yes, sir. In the 4 evaluation of teratological data. 5 If the Court permits, I would like to 6 clarify my previous answer to Mr. Griffin, being, no. 7 When I was asked if I was a professional a teratologist, that implied did I constantly -- 9 THE COURT: Excuse me, Dr. Epstein. 10 X don't recall hearing such a question. 11 THE WITNESS: I beg your pardon, sir, 12 I thought I was asked a question if I was professional 13 or expert. 14 THE COURT: Mr. Ehrlich, would you go 15 back to the question posed by Mr. Griffin and repeat C 16 it. 17 THE COURT REPORTER: "Question: Bottom 18 line. Doctor, are you attempting in this case 19 to qualify yourself as an expert teratologist? Ml MJ T > 20 K 21 "Answer: No." THE WITNESS: If the Court permits, I 0924017 22 would like to qualify that answer by saying I am not i 23 an expert teratologist in the sense that I perform 24 experimental teratology on a routine basis. However, 25 I am expert in the area of evaluation of teratological i BFG08030 19 Dr, Epstein - Direct 1 data in general, and in particular with problems of 2 risks to humans from exposure to teratogens in the 3 environment. 4 Apart from my publications in the area, 5 this is attested by my various governmental appointments 6 in areas including those in teratology, such as Chairmar 7 of Important Blue Ribbon Commissions, which dealt with 8 the -- the panel which dealt with teratological effects 9 of pesticides. 10 THE COURT: Do you wish to cross-examine 11 further? 12 MR. GRIFFIN: Yes, sir. 13 VOIR DIRE EXAMINATION(Continued) 14 BY MR. GRIFFIN: 15 & If I hear what you are saying, you are saying 16 although you are not an expert teratologist, you are 17 going to take some literature and you are going to 18 look at it and tell us what you think the literature 19 means as a teratologist would view it, is that fair? 20 A. I repeat what I said, that I have expertise in the 21 evaluation of teratological data, but I do not practice 22 teratology on a routine basis. 23 CL The same as any other doctor, you can read a 24 medical report on teratology and interpret it. 25 A No, sir, not the same as any other doctor in the BFG08031 20 Dr. Epstein - Voir Dire 1 sense that X am a person who has published extensively 2 in the areas of toxic chemicals in the environment, I 3 have advised government committees on this, I have set 4 up standards for government, and have very substantial 5 expertise in the evaluation of risks to pregnant women 6 from exposure to toxic chemicals in the environment, 7 ft Let me ask you this. Doctor: In the chemical B exposure cases in California Superior Court, in 9 San Francisco, where you gave a deposition in September 10 of 1982, did you testify, in answer to a question as 11 to your qualifications: 12 "First of all,the literature on this 13 is pretty modest in comparison with the over 14 whelming literature on teratology, and before 15 answering it I should also point out that I don't 16 hold myself out as an expert in teratology, so 17 the answers I will give you will be -- I won't 18 say poorly informed, but not expert, not that of 19 a professional." 20 A. Certainly. As I repeat again, X am not a 21 professional teratologist in the sense that X do 22 experimental teratology on a routine basis. X have 23 made that clear, I think. 24 ft I think we need to define teratology. What is 2S the science of teratology? BFG08032 21 Dr. Epstein - Voir Dire 1 A. Well, if we accept it as a science, teratology is 2 the study of birth defects caused by exposure to agents 3 in the environment, or in some instances simply just 4 the study of birth defects with no known exposure* 5 Q. And you, yourself, I gather, when you say you are 6 not expert in the field, means you have never conducted 7 such studies. 8A Mo, sir, that is not what I said. What I said 9 is, I don't conduct such studies on a routine basis. 10 I have conducted such studies. 11 In fact, let me be very specific. I 12 have specifically studied the fetotoxic and teratogenic 13 effects of N nitroso compounds in guinea pigs, and I 14 have several publications in this area. But, I don't 15 do this on a routine basis. 16 Ql And, you do not consider yourself an expert 17 teratologist, you have said so over and over again, IS haven't you? 19 A With due respect, the possibility exists that we 20 may be indulging in a semantic argument. 21 When I said I did not consider myself 22 an expert teratologist, that definition relates to the 23 routine practice of experimental or clinical teratology 24 That answer to that is no. 25 With respect to the evaluation of human BFG08033 22* Dr. Epstein - Voir Dire 1 risks from exposure to teratogenic agents, and with 2 respect to the evaluation of experimental data, I do 3 most certainly consider myself an expert, and in fact 4 I am so considered by a wide-range of government and 5 non-government bodies. 6 Q. Now, as far as this case is concerned, what you 7 propose to do is simply review literature and draw 8 some conslusions from it, correct? 9 A. No, that is not entirely the case. 10 Ql T1 A. What is entirely the case? I propose to produce to the Court statements from 12 the literature from which the Court can draw its own 13 inferences 14 In addition, I will be drawing inferences IS from those data which may or may not be consistent with 16 the statements in the literature. In other words, I 17 will be -- 18 Q. Thank you. 19 A. Excuse me, sir. 20 & Excuse me. 21 A. In other words I will be confining myself to my 22 area of expertise, which is the evaluation of data and 23 also the evaluation of human risk, which is my 24 professional area. 25 $ But, your professional area is not that of a BFG08034 23 Dr. Epstein - Voir Dire t teratologist, and what we areconcerned with in this 2 case is the evaluation of teratological data, aren't 3 we? 4 A. You are forcing me to be repetitive, sir. I am 5 experiment professional teratologist in the sense that 6 I do not perform experimental teratology on a routine 7 basis. 8 Ql That is -- 9 A. But, as far as the evaluation of data is concerned, 10 I am indeed expert in this area. 11 a And, in that area, you say you are not -- poorly 12 informed, but not expert -- you don't have the views 13 of a -- your views are not that of a professional. 14 A. Precisely. I am not an experimental teratologist. 15 Ql How, Doctor, if you are not expert in that field, 16 if you don't keep yourself up, as it were, with every 17 thing that goes on in the field, can you properly 18 evaluate literature in the field? That is what you are 19 doing. 20 A. Because, my expertise is in the area of evaluation 21 of toxicological data. 22 Toxicology is the study of the toxic or 23 adverse effects of chemicals, which includes carcino 24 genesis, cancer; mutagenesis; teratogenesis, birth 2S defects? acute toxicity? subacute toxicity? chronic BFG08035 24 Dr. Epstein - Voir Dire 1 toxicity. It is a wide-range * of adverse effects in 2 which I have substantial expertise. 3 Now, it is humanly impossible to be 4 performing all of these individual subareas of 5 toxicology on a routine basis. My profession is in B the evaluation of data on toxic effect, be it terato 7 genic or carcinogenic, together with a formulation of 8 opinions as to human risk. 9 MR. GRIFFIN: Well, your Honor, I have 10 no further questions. 11 THE COURT: I will permit the witness 12 to testify, and the jury of course will accept the 13 testimony from this witness in light of the answers 14 that he has given in which has expressed the reservatior 15 that the jury will evaluate. 16 You may present your case, Mr. Bolden. 17 DIRECT EXAMINATION(Continued) 18 BY MR. BOLDEN: 18 Ql Doctor, at my request, did you conduct an investi 20 gation into the pesticide Diazinon for the purpose of 21 determining its teratogenicity? 22 A. I did, sir. 23 Q And, as a result of that investigation did you 24 arrive at an opinion on its teratogenic properties or 25 potential? BFG08036 25 Dr. Epstein - Direct 1 A. Yes, sir. 2 Q. Would you please state what your conclusion is. 3 A. My conclusion is that there is a substantial 4 probability that Diazinon is teratogenic and represents 5 a teratogenic hazard to humans exposed to it. 6 Qi Would you please state how you arrived at your 7 conclusion and what underlying data you reviewed for 8 the purpose of forming your conclusion. 9 A. With the permission of the Court, I would like to 10 use one or two simple charts to explain the basis for 11 my opinion. 12 THE COURT: I haven*t any idea what you 13 are going to do here, Mr. Bolden. X can't rule on 14 the admissibility of a chart without an idea of what 15 it is all about. 16 THE WITNESS: May X respond, or do you 17 wish Mr. Bolden to respond to that? 18 THE COURT: I think Mr. Bolden should 19 respond to that initially. 20 MR. BOLDEN: Your Honor, as I understand 21 it from talking to Dr. Epstein last night and this 22 morning, he has prepared certain charts, actually three 23 charts, one of which summarizes the findings from 24 various studies of various kinds of animals as to wheth er 25 they were negative or positive for showing teratogenic BFG08037 26 Dr. Epstein Oirect 1 effects, and has listed them as summarized chart. 2 and another -- 3 THE COURT: Excuse me. Let's just 4 clarify one thing. Are these Or. Epstein's studies? 5 MR. BOLDEN: No. These are studies 6 from other -- 7 THE COURT: Are these from certain C 8 publications? 9 MR. BOLDEN: Certain publications. 10 THE COURT: And those publications will 11 be here to support those. 12 THE WITNESS: Yes, sir. 13 MR. BOLDEN: Yes, sir. 14 Do you have all of them here with you? m 15 16 THE WITNESS: I think so. THE COURT: All right. We will proceed. 17 We will deal with them on an individual basis. 18 A. This first chart, which I hope is visible is 19 listed as "Quotations Prom Literature on Teratogenicity mimm. h.j. t # 20 of Diazinon," and the chart contains two columns. h h ii 21 The column on the left is the author, 22 and the date of the statement. And on the right the 1 23 quotation is actually using the author's words. 24 If I may, I will proceed. 25 t MR- GRIFFIN: If your Honor please, I BFG08038 27 Dr. Epstein - Direct 1 object to this procedure. This seems to me, is nothing 2 more than picking words out of some study that is done 3 somewhere and trying to give those words probative 4 force, and they obviously can't have that; And, if S there is an exception to the Hearsay Rule, I think your 6 Honor should look at this whole picture to figure out 7 whether there is. It certainly has to be introduction 8 of an article, not words from it, and that this is just 9 an attempt to build an argument based on what is in 10 the literature, not an expose of the actual probative 11 effect of what it may be. 12 THE COURT: I will give you the full 13 opportunity in your cross-examination to probe all of 14 that. We will at this time proceed in this fashion. IS THE WITNESS: Thank you. 16 A (Continuing) The first article is by Khera, in 17 1968. Dr. Khera is a member of the Canadian Food and 18 Drug Administration, and Dr. Khera states that Diazinon 19 induced -- and, I quote, "congenital foot deformities," 20 in duck and chick eggs. 21 The next article by Kimbrough and Gaines 22 in 1968, Kimbrough and Gaines were government scientists 23 working at the Center for Disease Control in Atlanta, 24 states, and I quote: "Diazinon produced some mal 25 formations . " BFG08039 "The spontaneous incidence of malformatior s' -- well, no. That is fine. "Diazinon produced some malformations." The next is Green, 1969. "Diazinon produced teratogenic activity in all chicks.1* The next is Earle, 1973, United States Food and Drug Administration. "Teratogenic abnormality s have been observed in dogs given Diazinon. Teratogenic abnormalities have been seen in sows given Diazinon." That is pigs, miniature pigs. Nishiraura, a Japanese scientist, in 1973, "The following chemicals were proved to have a teratogenic effect: Diazinon." NIOSH, National Institute for Occupations 1 Safety and Health, 1978: "Based on the available evidence, Diazinon can be considered possibly teratogeni c and should be handled with caution by women of child* bearing age." Sax, 1979, a standard textbook on toxic chemicals: "Diazinon is 'an experimental teratogen.'" NIOSH, National Institute for Occupations 1 Safety and Health, RTECS, which stands for Registry of Toxic Effects of Chemical Substances, in 1977, in 1978, in 1979 and in 1980, states that Diazinon is a BFG08040 29 Dr. Epstein Direct 1 teratogen. 2 That, sir, is the first chart I wish 3 to draw to the attention of the Court. 4 The next chart relates to the actual 5 summary of the experimental findings on teratogencity 6 of Diazinon. 7 The chart is headed, "Teratogenicity 8 of Diazinon." And, I have attempted here to summarize 9 all the literature in which I am familiar, all the 10 studies done on Diazinon from the point of view of its 11 birth defect potential. 12 And, there are three columns here. The 13 column on the extreme left is the species, the animal 14 in which it was tested. The middle column is on the 15 author, including the date, and the right column is 16 on the results. 17 1 would like to stress at this stage 18 that this chart represents my most recent evaluation 19 of the literature. 20 I had in fact considered the literature 21 prior to a deposition last year, but since then I have 22 have the opportunity of going into the literature more 23 thoroughly, evaluating studies which I had evaluated 24 before, and also evaluating all evidence which has 25 become available to me. And, this is my evaluation of BFG08041 30 Dr. Epstein - Direct 1 the data, and in many instances such evaluation 2 actually reflects the author's own statements. 3 The first -- 4 MR. GRIFFIN: Excuse me, your Honor, 5 I don't like to interrupt, but here again- I have an 6 objection based on what the Doctor has now said. 7 Your Honor ruled in an Order that we 8 were to be able to take this Doctor's deposition since 9 he was held out as an expert. And, at the time of the 10 deposition he should be fully informed to; testify 11 about everything that he was going to testify to in 12 Court, that we could have advance notice. < 13 We took his deposition and got such 14 advance notice. Already he has come up with on the IS prior chart there, with studies for books that I haven't 16 had a chance to even look at. And now he says in his 17 testimony, I have since my deposition, I have gone and 18 done other work. And -- 19 THE COURT: I will -- 20 MR. GRIFFIN: Your Honor, I think he 21 shouldn't be permitted to do it. 22 THE COURT: I will have to limit him 23 to what he disclosed at the time of the deposition, Mr. 24 Bolden. He will have to -- whatever way he has to 25 tailor his testimony, he has to go back to what it was BFG08042 31 Dr. Epstein - Direct 1 at the time of the deposition! 2 We had a serious problem in this case 3 and we tried to resolve it as best we could by the 4 ruling that was made. He will have to conform to that S ruling. 6 BY MR. BOLDEN: 7 ft Do you understand that, Dr. Epstein? 8 A. Am I permitted to make a comment, sir? 9 THE COURT: No. I think the best you 10 can do is give us the testimony that you gave at the 11 time of deposition, or that which is consistent with 12 what you gave at the time of deposition. 13 If what you have learned since makes 14 a substantial change in your opinions or testimony, IS you will simply have to ignore it. 18 THE WITNESS: All right, sir. 17 THE COURT: We must conduct litigation 18 by certain rules. Doctor, and the rule that I made 19 earlier was that whatever was disclosed at deposition 20 is what would be the subject matter disclosed at trial. 21 A At the time of -- with further reference to this 22 chart, at the time of my deposition I stated specificalJ 23 that I had not yet completed my evaluation of the 24 literature and, therefore, the statements which I made 25 at my deposition reflect such incomplete evaluation. BFG08043 32 Dr. Epstein - Direct 1 To be specific^ I stated, "I don't think 2 I have really completed the work yet." Therefore, 3 statements at my deposition reflect such incomplete 4 evaluation, but I will proceed on that basis. 5 MR. McCANDLESS: Your Honor, X object 6 to the voluntary statement of the witness in response 7 to no question, and apparently in contempt of your ordez 8 in directions to him to try to limit himself to whatevei 9 it was -- 10 THE COURT: No. I think he was explainirg 11 that at the time of deposition he made the statement that 12 he was giving testimony based on incomplete data, and 13 I have simply ruled that whatever it was, that is what 14 he will be limited to. IS MR. GRIFFIN: Your Honor, I don't think 16 your Honor perhaps has actually looked at your Order. 17 Your Order stated that he is to be fully informed when 18 his deposition is taken. 19 THE COURT: And, all that 2 am ruling 20 now is that fully informed means that he will now 21 confine himself to what he had at the time of the 22 deposition. 23 The jury will ignore everything else. 24 We do operate according to rules here. 25 A. It is clear from the literature that a variety of BFG08044 33 Or. Epstein - Direct 1 studies have been done -- 2 MR. GRIFFIN: Excuse me. 3 If your Honor please, could I get the 4 Doctor to strike from the chart the post-deposition 5 literature he is referring to? e THE COURT: Was all of that that you 7 testified to earlier post-deposition? 8 THE WITNESS: Some of these data, sir, 9 are based on material which I hadn't examined at the 10 time, but which I have examined, but which are in the 11 published literature. 12 THE COURT: I will have to sustain the 13 objection. We will have to strike the references to 14 literature that was not referred to at the time of 15 deposition. i 16 That deposition was taken when? 17 MR. BOLDEN: -- 18 THE WITNESS : August of 1981. 19 THE COURT: All right. Not *81. 20 THE WITNESS : Yes, sir --- 21 MR. BOLDEN: August 26 of *81. 22 THE WITNESS : Yes, sir, of '81. 23 THE COURT: Nothing further was done 24 before trial? 25 MR. BOLDEN: Your Honor , I might add BFG08045 34 Dr. Epstein - Direct 1 that -- of course -- maybe I should do it at side bar. 2 THE COURT: Come to side bar. 3 4 as follows:) (Side bar discussion on the record, 5 THE COURT: How can you permit the case 6 to come to trial without updating the expert material? 7 MR. BOLDEN: Your Honor, the literature 8 9 THE COURT: I was surprised when he said 10 August '81. I thought he meant *82. 11 MR. BOLDEN: All the literature we 12 are talking about is literature which came from Ciba13 Geigy's files which was made -- if I am not mistaken -14 all of the literature are their published works, all of 15 it was in Ciba-Geigy's files. 16 We may have had some of it ourselves, 17 but it was all turned over to us as part of the studies 18 -- not studies, part of the documents which Ciba-Geigy 19 produced. 20 MR. EISENHART: All that was made avail 21 able to them well prior to the deposition. 22 MR. SPALDING: That is not true. 23 MR. BOLDEN: That particular statement 24 is not true. 25 MR. SPALDING: Your Honor, you will BFG08046 35 Dr, Epstein4- Direct/Side Bar r remember the controversy arising over my trip down 2 to Greensboro when they refused to produce the documents r 3 here in Philadelphia. Then we had the controversy 4 over the copying of the documents, whether they would 5 be brought up to Philadelphia to be copied, or copied * 6 down there at our expense and transported up. 7 Thereafter, the copying did occur and i c 8 was sent to us. 9 In addition to that, there was also 10 a study that'was done by Ciba-Geigy, which I don't < 11 believe was completed until August of 1981 -- 12 THE COURT: Let me just -- c 13 MR. SPALDING: -- which could not be 14 turned over to the Doctor. Hi HIM 15 THE COURT: Why was not an updated c 16 report given to opposing counsel long before now? 17 MR. SPALDING: The doctor never prepared 18 T 1MMI 19 THE COURT: If the expert was going to 20 rely on additional materials, why was it not disclosed 21 before trial? 22 MR. SPALDING: The only materials that * c c i 23 he is relying on in addition to those which he himself l *A 24 obtained, are the material which Ciba-Geigy has in its c 25 own files. M ( BFG08047 36 Dr. Epstein - Direct/Side Bar 1 MR. BOLDEN: That is not his question. 2 THE COURT: The question is, why was it 3 not disclosed that this expert was going to rely on 4 material that was in Ciba-Geigy's files, material that 5 was included in other publications, whatever, so that 6 they could be prepared in the expert area where 7 required 8 You are required to -- there is not 9 much sense in my talking. 10 MR. SPALDING: It is somewhat implicit 11 that the published material -- 12 THE COURT: I was simply noting that 13 I stopped speaking because you distracted Mr. Bolden's 14 attention. Whatever it was, I lost my train of thought 15 You may proceed. 16 MR. BOLDEN: Your Honor, your Honor 17 of course is right. The only thing I can say is that 18 in the interests of fairness, that because the litera 19 ture we are now talking about comes from Ciba's files 20 and is published literature, that it is difficult to 21 see how any substantial prejudice would result to them 22 from permitting this witness to testify, not only to 23 what he previously testified to, but simply supplement 24 or -- and add to whatever conclusions he had arrived 25 at at the time of his deposition. BFG08048 37 Or. Epstein - Direct/Side Bar 1 X might say, for instance, that one of 2 the things I believe he intends to say is that he made 3 -- he made a mistake on the Ciba report which would be 4 favorable to Ciba which he intends to point out. But, 5 under your -- if your Honor forbids him from even 6 stating what he has been able to review since the time 7 of the deposition, it places us in a very awkward 8 position. 9 THE COURT: Did he state an opinion 10 at the time of this deposition? 11 MR. BOLDEN: Yes. Yes. 12 THE COURT: All right. You will confine 13 your direct examination to what he presented at that 14 deposition. I suspect that cross-examination will open IS the door to what he has learned since, and X will rule 16 upon it at that time. 17 MR. BOLDEN: Thank you, your Honor. 18 THE COURT: But, at this time, since 19 this was all -- the deposition was given in August of 20 '81? 21 MR. BOLDEN: Yes, your Honor. 22 THE COURT: We are now in December of I 23 *82, and no update was given. ( I'm going to confine him ( 24 to what he gave. 25 MR. BOLDEN: Okay. BFG08049 38 1 Dr. Epstein - DirecVSide Bar THE COURT: And, if it becomes pertinent 2 I will allow the door to open. 3 MR. BOLDEN: May I explain that to him 4 at side bar so he understands it very clearly? 8 t 6 THE COURT: Yes. MR. GRIFFIN: As a practical matter. 7 your Honor, if I am going to cross-examine the Doctor, C 8 and that is the whole purpose of your Honor's ruling. 9 to give me a fair chance to do that, he is going to be 10 able to use literature and things I have never seen I 11 that I will not have time to look at before I go into 12 cross-examination, that I will not have time to go over C 13 it with my expert. He has just a plain unfair advantagt 14 and that is the purpose of the ruling, and, when your rM in 15 Honor said, well, as soon as Griffin opens his mouth, < 16 we will let him spew all this at you -- 17 THE COURT: I didn't say that. I think 18 I anticipate that your questioning is precisely going t< 19 open the door, and it may well. I have not ruled that nut** iiH ii. M4. 20 it will. I am simply saying we will consider at that 21 time whether I will relax the rule and allow him to f rA J,V P A ^ 22 testify concerning this. 23 i 24 MR. GRIFFIN: All right, sir. THE COURT: You will have to try to 25 guide yourself accordingly. K BFG08050 39 Dr. Epstein - Direct/Side Bar 1 MR. GRIFFIN: My objection -- it seems 2 to me the whole purpose of this is to avoid that kind 3 of thing for the poor attorney who is trying to get 4 himself ready to try a case. We are dealing in the 5 field we know not ourselves. All we can do is take 6 advice from others, and if we don't have the time to 7 get the advice ahead of time, we are unduly strapped. B THE COURT: Yes, I understand. 9 MR. BOLDEN: Your Honor, in his direct 10 examination will he be permitted to correct an error 11 he made? Now, this is not a question of supplementing 12 new literature. It is a question of clearing up an 13 area -- 14 MR. GRIFFIN: He is just anticipating IS cross-examination. 16 THE COURT: Well, I think he has a 17 right to. IS 19 MR. GRIFFIN: He can if he wants to. THE COURT: Yes, and I think he should. 20 MR. EISENHART: He was reading this 21 chart backwards at deposition, Mr. Bolden. 22 (End of side bar discussion.) 23 THE COURT: Members of the jury, we 24 have had a long discussion here at side bar, and it 2S requires Mr. Bolden to make a statement out of your BFG08051 40 Dr. Epstein - Direct 1 hearing to his witness in order that he may conform 2 to the ruling I made at side bar. 3 (Off-the-record discussion between Mr. 4 Bolden and the witness.) S A. In further response to the questioning, let me 6 just summarise the previous chart where the quotations 7 from the literature on the teratogenicity of Diazinon. 8 There were at least eight statements 9 in the literature going back to 1968 that Diazinon 10 is teratogenic, produces birth defects. Four of these 11 statements come from actual people who have conducted 12 the experiments. So, the actual people who conducted 13 the experiments in four instances -- let me return 14 to the previous chart, if I may, the previous one which 15 I have just completed. 16 (The chart is made available for the 17 witness.) 18 A. Thank you. 19 The people who did the experiments in 20 this list include the first one, Khera, 1968; Kimbrough 21 and Gaines, 1968; Green in 1969; and Earle, 1973. 22 Now, to come back to the summary of the 23 teratogenicity of Diazinon, if I can trouble you again, 24 sir. 25 (Another chart is made available for BFG08052 41 Dr. Epstein - Direct 1 the witness.) 2 It is clear that there have been some 3 where in the region of 13 studies on the teratogenicity 4 of Diazinon. These studies have involved eight species 5 And, I think it is necessary to emphasize to the Court 6 that these studies have not produced uniform results. 7 They are a mixed bag. 8 In some of the experiments Diazinon 9 was shown to be teratogenic and in some of the experi 10 ments it was shown not to be teratogenic. Some of the 11 experiments are better than others, some of the experi 12 ments are worse than others. In other words, it is 13 difficult to place equal weight on. all the experiments 14 whether positive or negative. 16 But, it is necessary for me to explain 16 the difference between positive and negative data from 17 a toxicological standpoint. 18 In toxicology, in the study of -19 MR. GRIFFIN: Your Honor, what question 20 is being answered now? 21 THE WITNESS: I am -- 22 THE COURT: I think he is outlining and 23 summarizing certain information from studies. He may 24 proceed. 2S THE WITNESS: Thank you, sir. BFG08053 42 Dr. Epstein - Direct 1A In the chart which you see in front of you, you 2 will see some pluses and some minues in the extreme 3 right-hand column. And, before getting into any 4 specifics, I would like to explain the difference, the 5 difference in toxicological significance between a e positive study and a negative study in toxicology. 7 In general, a positive study -- finding 8 a result in a toxicological test, be it study of birth 9 defects or cancer, supersedes a negative study. In 10 other words, if you have a positive finding of an 11 adverse effect in any one system, this result is much 12 more important than a study in which you failed to t3 find an effect. And the reason for this is very very 14 clearcut. The reason for this is, toxicology is a 15 very insensitive subject. It is a very very insensitive 16 discipline and it is terribly important to get this 17 point across before we get into the specifics of any 18 positive and negative studies. And, with the permission 19 of the Court, I would like to explain why toxicology 20 is an insensitive subject. 21 Let us say we introduce into the 22 environment an agent which induces 1 in 10,000 cancers, 23 or 1 or 10,000 birth defects, okay? Therefore, in the 24 United States alone, that one agent would be responsible 25 for 20,000, or 20,000 cancers a year, which would be BFG08054 43 Dr. Epstein - Direct a national calamity. Now, what are our chances of picking up such an effect in experimental systems? Now, let us assume that the sensitivity of a rat, or mouse, or guinea pig to a particular agent is the same as that of a human being. Therefore, if you were to test in animals at the same levels as you test in humans, you need 10,000 rats, or 10,000 mice in an experiment to get one adverse effect, one cancer or what have you, and for statistical significance you may need 20,000 rats or 20,000 mice. In an attempt to reduce this insensitivii. of animal tests compared to large human populations, we tend in animal tests to test at levels higher than those of human exposure. But, the fact is this: When you are dealing in an animal test with 20 or 30 or 10 animals, this is very insensitive, and your chances of picking up an agent which induces birth defects or cancer, in one in a thousand, is virtually nil; in one in a hundred can be virtually nil. Therefore, you have got to understand, toxicology per se is a grossly insensiti ve subject. It is grossly insensitive because we test for very small numbers of animals compared to massive human populations at presumptive risk. And, this is an BFG08055 44 Dr. Epstein - Direct 1 axiura in teratology, and in toxicology in general, that 2 a positive result, unless in a study of course that has 3 controls, and doesn't -- and in which other advers 4 effects have not been introduced, that a positive resul 6 is very much more important than a negative result. 6 Cl Doctor, can I stop you in your explanation to ask 7 you one question with respect to that. 8 Is there anything from recent history 9 of the last 30 years that demontrates a point that a 10 negative study is superseded by a positive study? 11 A. Let me tell you about thalidomide. 12 & Is the answer yes? 13 A. The answer is yes. And, thalidomide is a most 14 excellent example of this. IS Rats and mice are somewhere in the 16 region -- mice are somewhere about 700 times more 17 resistent to thalidomide than humans -18 MR. GRIFFIN: Do I have to try a 19 thalidomide case? I have enough trouble with the 20 Diazinon case. 21 MR. BOLDEN: Your Honor, he doesn't 22 have to try a thalidomide case, but I believe this 23 witness is entitled to explain why a positive and a 24 negative study have different implications. And, if 2S he has to do it by illustration, I believe that is an BFG08056 45 Dr. Epstein - Direct 1 appropriate way of receiving it. 2 THE COURT: All right. But, he should 3 be careful not to intrude in an area where an objection 4 has been made and until it has been clarified. S THE WITNESS: Yes, sir. 6 THE COURT: I will permit it, but I will 7 caution Dr. Epstein once, and I hope I won't have to a caution him again: When you hear an objection. Doctor, 9 be very circumspect and very careful about what you say 10 until we get a clear ruling. 11 You may proceed along that line. ia A My point about thalidomide is not wishing to get 13 into any aspect of this, but merely to talk about 14 problems of insensitivity of animal tests. 15 There are many occasions in which you 16 can demonstrate that animal tests are very very insensi* 17 tive and, therefore, when you get a positive in an 18 animal test, this is a lighted beacon, and ignore this 19 at the peril of society. 20 21 CL Now, to come back to the -- Just one second. Doctor. With respect to that 22 statement, as it related to the experience that actually 23 happened in the thalidomide situation, how does that 24 relate to the positive-negative aspect of what you were 25 talking about? What was demonstrated there? BFG08057 46 * Dr. Epstein - Direct 1 A. Well, to the best of my recollection, thalidomide 2 is -- the teratogenic effects of thalidomide in mice 3 are 700 -- mice are 700 times more resistent. Therefore 4 testing -- 700 times more resistent to thalidomide 5 than humans. And, therefore, one could easily have 6 missed the teratogenic effects of thalidomide using 7 rodent species. And, therefore, this is the principle 8 in toxicology in general, not only in teratology, but 9 in carcinogenesis, and the full area of toxic chemicals 10 in the environment, the insensitivity -- 11 THE COURT: Just a moment, Dr. Epstein. 12 You offered thalidomide as an example. Were tests 13 conducted and did it in fact fail to reveal something? 14 Is that what you are trying to get across? 15 THE WITNESS: Essentially, the only 16 point I am making is that you have major variations 17 in sensitivity from animal species to humans -- 18 THE COURT: No. Would you just answer 19 the question. Were some tests conducted? 20 THE WITNESS: Yes, sir. 21 THE COURT: Well, this is the only 22 significance, it seems to me, that your earlier comment 23 could have. And, if you would address yourself to that 24 BY MR. BOLDEN: 25 Q, Were there differences in animal speci that were BFG08058 47 Dr. Epstein - Direct tested with respect to thalidomide that produced different results? A. Yes, there are. Q. Explain that. A But I must stress we are dealing with two factors here, both of which I would just like to segregate because there may be ambiguity. One is the insensitivity of animal tests in general. Animal tests, irrespective of whether they are mice, rats, guinae pigs, monkeys, what have yoi. are insensitive because you only test a very small number of animals compared to very large human popula tion. That is one problem. The second problem is differences in sensitivity from species to species. Some species are much more sensitive than others and others are much less sensitive than others, and you don't have any way in advance of knowing whether humans are more sensitive or less sensitive. Humans could be very much more sensitive to a particular cancer-causing agent, or birth defect cancer-causing agent. And, the importance of thalidomid lies in relation to this -- that thalidomide -- humans were much more sensitive to thalidomide than animal tests, particularly mouse and rat tests. BFG08059 48 Dr. Epstein - Direct 1 How, to get back to -- I must apologize 2 for that long explanatory note. But, to get back to 3 the summary of teratogenicity of Diazinon, here you 4 see about 13 studies done on teratogenicity of Diazinon 5 mixed results: some positive, some negative. 6 The previous chart had statements from 7 four of the people who conducted these studies who 8 clearly concluded that they are -- they were positive. 9 How, my interpretation of the data, 10 therefore, is weighed in the favor of -- there is a 11 frank bias in the direction of positive data. I am 12 biased in the direction of positive results for the 13 reasons which I have explained. That is number one 14 bias. 15 The second is that I don't believe that 16 any one of these studies -- that -- I am not proposing 17 that the inferences that I draw on teratogenicity of 18 Diazinon rests exclusively on any one of these positive 19 studies. They rest on the aggregate of the data. 20 In toxicology, you examine individual 21 studies and you draw inferences from them, whether they 22 be positive or negative, but you also examine all the 23 positive studies together an you look at all the nega 24 tive studies together. And, it is possible that in 25 some instances you may say, well, I'm not terribly BFG08060 49 Dr. Epstein Direct 1 happy about that one positive* study alone, but that one 2 positive study together with other positive studies 3 creates a more persuasive position, and that is 4 basically my feeling in the matter. 5 I subscribe to the position in the 6 literature that Diazinon is teratogenic, and the basis 7 for this rests on some of these studies here. 8 Now, I should point out, and I gather 9 that 1 have the Court's permission to explain this, 10 that there are some discrepancies between my listings 11 of positive results here and negative results here, 12 and those at the time of my deposition, because, as I 13 indicated before, I had not completed my evaluation of 14 the literature. And, I will be very specific as to 15 these. 16 For instance, the first three studies - 17 the first two studies I call positive here, and at the 18 time of my deposition I said they were negative. That 19 is because 1 did not have access to a paper which I 20 have in court which states -- the paper -- another 21 paper by the authors which states that the duck egg 22 and the chick egg study were both positive, and I did 23 not have that paper with me at the time. And, there C 24 fore -- % 25 MR. GRIFFIN: It seems to me this is C 2 BFG08061 50 Dr. Epstein - Direct < 1 precisely just the opposite what your Honor ruled. 2 THE COURT: No, no. We said that there 3 would be a clarification of a mistake. Now, is this -- 4 MR. GRIFFIN: This is not it, sir. S Be is simply using articles that you told him not to 9 6 use and he is now saying, now look, I am only going to 7 use three. Here are the three results. Now, one of 4 8 those he didn't have before. Here are the three result:; 9 and I want you all to know I am taking those out, but 10 he is just repeating them and left them on the chart. %&. 11 I don't know these cases that he is 12 bringing up now. I never heard of them before. 4 13 THE COURT: I am not sure I understand 14 exactly what it is everyone is saying here. 18 Members of the jury, I ruled at side bar 4 16 it was brought to my attention that Dr. Epstein had 3 :* 17 made a mistake at the time of his deposition,, and that 18 he has since learned that it was a mistake, and I did 1 19 allow him, or gave permission that he could clarify thai m s 9 t 20 he did in fact make a mistake, even though it was based < 3 21 upon information that he obtained later. 4 22 Now, let's not go beyond that. And, 23 Dr. Epstein, don't you go beyond that. 24 BY MR. BOLDEN: 25 Qi Dr. Epstein, specifically as it relates to the t BFG08062  51 Dr. Epstein - Direct t4 1 mistake, confine yourself to the Ciba in-house study. 2 A. I beg your pardon. I was under the impression C 3 I was allowed to correct mistakes. 4 0- Not at at this point. Just the mistake -- that r 5 specific mistake. 6 A. I understand. I understand. Therefore, as far 7 as the first two studies are concerned, the authors l 8 themselves, the Khera and Lyons, and Green, all have' 9 stated that those results are positive. I will not 10 be discussing those further at the moment. < 11 MR. GRIFFIN: Are those ones you did 12 not tell me about in the deposition? c 13 THE WITNESS: In the previous chart, 14 I listed Khera and Green as stating that they induced 15 congenital abnormalities. I am not discussing this now, 4 IS I had this up on the previous chart. On the previous 17 chart I had a quote from Xhera that it induced 18 congenital deformities. I have already discussed that 19 and I have already discussed Green's statement that M l M M - Jta T 'IHM I--4 J K W H 20 Diasinon was teratogenic and, therefore, 1 was referring 21 just then exclusively to statements in the literature o s o frz fin r: 22 in the previous chart. l 23 MR. GRIFFIN: I just wanted to make sure 24 that we were doing that. Doctor. 25 i THE WITNESS: Oh, yes. BFG08063 52 Dr. Epstein - Direct 1 MR. GRIFFIN: We are not dealing with 2 any literature subsequent to your deposition# right, 3 and you are not calling any such literature to the 4 attention of the jury, right? 5 THE WITNESS: In the previous chart I 6 have made statements in the literature on the 7 teratogenicity of the Diazinon. I am now discussing a my analysis of the experimental data which is different 9 from making quotations from the literature. 10 THE COURT: Did you understand that my 11 ruling comprehended the chart as well? 12 THE WITNESS: This chart as well, I 13 understand -that, sir. 14 THE COURT: Not this chart, the chart 15 you earlier referred to. Is that the chart that you 16 earlier referred to? 17 THE WITNESS: No. The previous chart 18 on quotations from the literature was a different one 19 to this. 20 THE COURT: All right. 21 THE WITNESS: This is an analysis -- 22 THE COURT: With respect to the previous 23 chart on quotations from the literature, the restriction 24 applies there as well. 25 THE WITNESS: I understand. BFG08064 53 Dr. Epstein - Direct 1& In the time of the deposition there was one 2 particular -study, a Ciba-Geigy study in 1974 which I 3 took the position that it was positive. On further 4 evaluation of those data in the sense that I evaluated 5 all the data too, not only that, I have discovered that 6 I misread one particular table and I am changing that 7 positive result to a negative result. a Therefore, this is in accordance with 9 the Judge's ruling. I will restrict my comments 10 exclusively to that particular change, although there 11 have been changes in the other direction which I am 12 precluded from discussing. 13 Therefore, let us come back to the 14 totality of this chart. The totality of the chart IS demonstrates there are negative studies and positive 16 studies. 17 THE COURT: Dr. Epstein, you do under 18 stand English, don't you? 19 THE WITNESS: I will not make any. 20 further reference -- 21 THE COURT: Not again. You have done 22 it twice so you feel it won't be necessary to do it 23 again, is that right? Now, Doctor, don't play games 24 with me. I have told you, you have been told by 25 counsel, to refer to nothing after the deposition. BFG08065 54 Dr. Epstein - Direct 1 except to correct that one mistake. Don't do it again. 2 A. Ignore the last column on results. Let me simply 3 say that these studies are -4 MR. GRIFFIN: Excuse me, your Honor, 5 if we are going to ignore the last comment, can we just e take it off? If part of it is supposed to be ignored, 7 let's not play with it. S THE COURT: Is that the chart we are 9 talking about? 10 MR. GRIFFIN: Yes, sir. 11 THE COURT: Yes. 12 MR. GRIFFIN: He says they are not 13 appropriate and there are things he says to ignore. 14 Let's not use it. IS THE WITNESS: May I just make the change: 16 in the chart to reflect the statement at the time of th<i 17 deposition? 18 THE COURT: You may make a change to 19 reflect what was included at the time of the deposition 20 and we will block out the rest. 21 THE WITNESS: Thank you, sir. 22 Could I borrow your red pen, sir? 23 THE COURT: Counsel have in mind, of 24 course, the time limit we put on for this morning. 2S MR. GRIFFIN: I would like to suggest. BFG08066 55 Dr. Epstein - Direct 1 why don't we take a little recess and redo the chart? 2 He still has the same old chart right in front of us 3 with all the old things on it. 4 THE COURT: We will get it out at a 5 recess. At the moment the jury, I am sure, is not 6 going to keep looking at that chart. 7 THE WITNESS: Thank you. 8 A. I have crossed out the previous results. 9 MR. GRIFFIN: I would -- 10 THE COURT: Any more than the jury is 11 going to keep listening to Dr. Epstein's comments 12 that I told him not to make. 13 Now, let's move along. We do have some 14 time problems this morning. 15 THE WITNESS: With apologies to the 16 Court, I will try and be as precise and clear as 17 possible. 18 A The new figures which I put in, the new signs, 19 are the statements of positive and negatives which I 20 made at the time of the deposition, and again as I 21 mentioned before -- these are a mixed bag: some are 22 positive, some are negative. That in fact represents 23 a brief summary of the teratogenicity of Diazinon. 24 BY MR. BOLDEN: 25 $ One further question before we leave this topic. BFG08067 56 Dr* Epstein - Direct 1 Is there any particular signi-ficance in any specific 2 study to the fact that a low dose, or low number of 3 animals are used in the study? 4 A. Yes. If in the study you use a low number of 5 animals, yo-u make that set -- that test more insensitive. 6 You reduce the sensitivity of the test. Therefore, 7 any negative inference or any negative conclusion 8 based on a study with a small number of animals, I 8 would not accept and I don't think any professional 10 toxicologist or expert in the area would accept a 11 study based on very small numbers of animals. 12 However, a positive finding in a 13 study based on a small number of animals is entirely 14 different. A positive study means that you are really IS dealing with a very, very marked effect, especially 16 if this effect is seen in the test animals and not in 17 the control animals. 18 Therefore, for this reason when I and 19 others have sat on government committees drawing up 20 guidelines for testing numbers of animals, for testing 21 numbers of animals in a toxicology test, we have been 22 very very careful to insist that in an attempt to reduce 23 the insensitivity of tests, in an attempt not to have 24 what we call a false negative -- and, a false negative 2S is, you test a compound which induces cancer or birth BFG08068 57 Dr. Epstein - Direct I defects, and you miss it in animals, which is the worst 2 possible thing that can happen -- in an attempt to 3 prevent this, you like to have a reasonable number of 4 animals. S Now, the definition of reasonable varies 6 from time to time. However, a positive result, when 7 you have a small number of animals, is very significant 8 because it means even with this insensitive test, even 9 with a small number of animals, you are getting adverse 10 effects, you are getting your cancer or your birth IT defects. 12 So, therefore, the answer basically is 13 that you would like to have a reasonably well defined 14 study with a reasonable number of animals, that a nega 15 tive inference from a study of small animals is just 16 not acceptable whereas a positive inference may well be 17 acceptable. 18 ft Doctor, have you formed an opinion as to whether 19 or not the spraying of Diazinon at the Amtrak facility 20 at Cornwells Heights by Orkin Exterminating Company, 21 was or was not a substantial factor in causing the 22 complete unilateral cleft palate and cleft lip which 23 the infant Khristine McConnell was born with? ; 24 K Yes. 25 ft What is your opinion? BFG08069 58 Dr. Epstein Direct A. My opinion is that there is a substantial probabil-. t: that the exposure of Mrs. McConnell to the Diazinon was the contributory factor or the cause of her birth defect. ft Can you explain why you arrived at that opinion? A. The conclusion is based on two major sets of considerations. The first is that she was exposed to a teratogenic pesticide, a pesticide causing birth defects, in her first trimester of pregnancy; that is, in the first three months of pregnancy. That is the particularly sensitive time when birth defects can occur. And, as I indicated before, the reasons for my statements on the teratogenicity of Diazinon come from my evaluation of the literature and also statements in the literature. So, that is one set of considerations. The second set of considerations relate to the fact that there were no other known predisposing factors. There was no family history, no -- the first child was normal, she took no teratogenic drugs; there were no ether recognized causes of birth defects to whict she was exposed in her first trimester. So, it .rests basically on positive data, the exposure to a terato genic pesticide in the first trimester, and the negativ .cn frZ G O Z BFG08070 59 Dr. Epstein - Direct 1 data, the absence of exposure*to other known teratogens 2 or the absence of other known predisposing factors. 3 MB. BOLDEN: May I have a minute with 4 counsel? 5 (Pause) 6 ft Did you consider any specific records or spraying 7 records in arriving at your conclusion? 8 A. I examined the records, but have not used the 9 records as a basis for quantitative determination of 10 exposure, but*for qualitative determination of exposure. 11 Cl How many exposures would be needed to produce 12 the result that we have been talking about? 13 A. I can't, with due respect, answer that question 14 simply. 18 The induction of an adverse effect 16 such as teratogenic birth defects or carcinogenic, 17 follows what we refer to as a dose response situation. 18 The more the material you are exposed to the greater is 19 the chances, the greater are the chances of an adverse 20 effect. 21 Now, when I say the more of the material 22 I am exposed to, that is a function of two factors: 23 one, the actual level of the material or the dose of 24 the material at any one time: and, two, the duration of 25 the time. So, you have two factors: one, the duration BFG08071 60 Dr. Epstein - Direct 1 of exposure to the material itself, and, two, the actuaj 2 concentrations at any one time. 3 So, the more you are exposed to and the 4 longer you are exposed to it, clearly the greater are S the risks. The lesser you are exposed to it, the 8 shorter period of time, the lesser are the risks. But, 7 there isn't a stage at which you can eliminate any 8 possibility of a risk. You just say the risks are 9 lower with lower exposures and with shorter periods of 10 time. 11 Ql With respect to Diane McConnell, what time period 12 and what exposure were you using in arriving at your 13 opinion? 14 A. The basic period of time which clearly one has IS maximal interest in is the sixth to the ninth week of 16 pregnancy. That is the most sensitive time for the 17 formation of the palates. 18 Mow, therefore, the month of December 19 is clearly more significant than the month of October. 20 However, I am not prepared to exclude the possibility 21 that there are residues from the month of October, and 22 I can elaborate on that if you so wish me to. But, it 23 is the month of December which clearly is the most 24 critical time from the point of view of exposure. 25 For instance, on the 7th of December, BFG08072 61 Dr- Epstein - Direct 1 when he was seven weeks pregnantf I understand that she 2 was only present at work for a short period of time 3 that day, probably three-quarters of an hour or an 4 hour. I don't have full details on that. My infomatio 5 on that is somewhat derivative. But, she did return 6 to work eleven days later when she was about eight-and- 7 a-half weeks pregnant then. Therefore, during the time 8 of the single exposure on the 7th of December, and 9 subsequent exposure on the -- when she returned to work 10 on the 18th, that is clearly a time for which one has 11 concern, and also time subsequent to that time after 12 the 18th of December during which time she was exposed 13 to, presumably, to residues in the environment. So, 14 that is one set of exposures. 16 Therefore, let me go over this, if I 16 may, a little more clearly. There was the exposures on 17 the 7th of December for a short period of time, and 18 from the 18th of December onwards. There was a 19 transient -- that is one thing. And then in addition, 20 there was a residue from the exposure on the 5th of 21 October of the Diazinon, and we can discuss this in 22 a moment; and, also, perhaps of significance, although 23 I can't be too certain of this, an impurity, a very 24 stable impurity in the Diazinon called sulfotep, which 25 is highly toxic and highly stable. BFG08073 62 Dr. Epstein - Direct 1 So, essentially, we are discussing 2 basically the December episode but possibly residues 3 from the October spraying. 4 There is also one other possibility, 5 which has to be considered, and that is that there were 6 breakdown products in her body, persistent breakdown 7 products in her body following the October spraying. 8 We do know that for one-to-tvo months 9 after exposure to Diazinon there can be breakdown 10 products of the Diazinon which can be recovered from 11 the body. And, we don't know, therefore, what signifi 12 cance these have in terms of teratogenic effects. 13 Therefore, because of these areas of 14 ignorance I would prefer to concentrate on the December IS spraying , particularly the December spraying on the 16 period of time on the 7th and after the 18th, but I 17 am not prepared to exclude residues from the 5th of 18 October and -- residues in the environment from the 5th 19 of October -- residues in the environment from the 20 5th of October, especially as the literature is very 21 clear that residues can persist for a long period of 22 time, and I am also not prepared to exclude the possi 23 bility that there are some metabolic or degradation 24 products in her body which may also have played a role 25 in the teratogenic effects. BFG08074 63 Or. Epstein - Direct 1 MR. BOLDEN: Your Honor, that concludes 2 my direct examination of Dr. Epstein. But,'what I 3 would like to request the Court's indulgence for, 4 because it would only take until 11:30, I believe, 5 is that if counsel would permit me to examine Dr. 6 Hulnick, who is here, I am reasonably confident that 7 his examination should only take five or ten minutes. 8 THE COURT: Do you have any objection? 9 That way we can start the cross-examination and not 10 interrupt it. We are only going to have a few minutes tl anyway. 12 MR. GRIFFIN: No, I have no objection, 13 sir. 14 THE COURT: Thank you. 18 16 17 18 stand.) 19 Would you step down. Dr. Epstein? THE WITNESS: Yes, sir. (Witness withdrew from the witness (The jury entered the courtroom at 20 2:35 p.m.) 21 THE COURT: Good afternoon, members of 22 the jury. I was happy to hear that you were all so 23 jolly out there. 24 You may commence your cross-examination. 25 Mr. Griffin. BFG08075 64 ( 1 (Dr. Samuel Epstein resumed the witness 2 stand.) r 3 CROSS-EXAMINATION 4 BY MR. GRIFFIN: 5 CL Doctor, this is not the first case in which you r- 8 have been engaged as a witness, is it? 7A No. < 8& Maybe 12 other litigations you could recall 9 quickly? to A Yes, by all means. c 11 Q. And, you have testified with respect to a number 12 of different substances, right? * 13 A May I take your questions one at a time? 14 Q. 1 thought you answered it. 15 A I was going to answer that the -- < 16 THE COURT: Just a moment. Would you . HW W 17 give me the question and let*s see if the question 18 was completely answered. 19 THE COURT REPORTER: "Question: Doctor, X 20 this is not the first case in which you have 21 been engaged as a witness, is it? 22 "Answer: No. 23 "Question: Maybe 12 other litigations 24 you could recall quickly? 25 "Answer: Yes, by all means." BFG08076 65 Dr. Epstein - Cross 1 THE WITNESS: X am sorry. I didn't 2 hear "twelve." 3 THE COURT:. Did you say twelve? 4 MR. GRIFFIN: I was not asking him to 5 list them. 6 7 twelve? THE COURT: No, no. Did you say 8 MR. GRIFFIN: I said twelve. 9 THE WITNESS: I am happy to accept 10 that. 11 A. I haven't testified that number of times. 12 Ql The various cases required many different substance 13 A. That is correct. 14 Q. Am I not correct that in everyone of those cases 15 other than this one, you were really testifyin? about 16 carcinogenicity? 17 A. No, that is not true. 18 Qi Have you testified about teratogenic effects 19 cause and relationship in any of those cases? 20 A. No. Teratogenesis was not the issue, but 21 carcinogenesis also was not the only issue. For 22 instance, there was a case in 1974 or '75 -- 23 0. Well -- 24 A. -- in which workers were exposed to a chemical 25 that produced, in a plant in Columbus, Ohio, and this BFG08077 66 Or. Epstein * Cross 1 chemical produced paralysis in workers, and I testified 2 on behalf of that. So, there have been areas other 3 than questions of cancer. 4 Q. Well, for my purposes, to put it the other way 5 around, you have not testified in a case before claiming 6 that there was a cause-and-effect relationship between 7 a chemical and a birth defect. 8 A. Correct, sir. 9& When you were engaged in this case, did you 10 consider whether you should tell the plaintiffs' 11 lawyers they should get themselves a teratologist? 12 A. I made it very clear to the counsel for plaintiff 13 what my areas of expertise are and have been, and what 14 in what areas I could be helpful to them. I made it 15 clear to them that I wasn't a bench teratologist in 16 the sense of doing experimental work on teratogenicity, 17 but I also pointed out that I had had extensive 16 experience in the evaluating of teratogenic hazards, 19 teratogenic data, and in the formulation of opinions 20 on risks of birth defects from people exposed to 21 teratogens. That I made explicitly clear to Mr. Bolden 22 at the time when he first approached me. 23 Q. Doctor, my question was, did you consider referring 24 him to a teratologist? 25 A. I said to them that I was not a bench teratologist - BFG08078 67 Dr* Epstein - Cross 1 Q. I am not asking you what you said to them. 1 am 2 asking, did you consider referring them to a teratolo- 3 gist? 4 A. Yes, I did. 5 Cl All right. In the course of that consideration, 8 did you come up with the name of a teratologist who 7 you thought would give the kind of testimony you have 8 given in this case? 9 A. Well, 1 -- that would be presumption on my part 10 to predict what testimony another expert would give. 11 Qi You know men all over your toxic field, don't you, 12 or throughout the country, you have been on panels and 13 you .have worked on governmental things, you know men 14 in this area, don't you? 16 A But I do not predict or would not be so presumptuoi 18 to predict the nature and the type of testimony that 17 another expert would give, especially prior to their -18 evaluation of the data. 19 Cl Let's just put it this way. Doctors If somebody 20 comes to me with a question, with a legal question, 21 and I say to myself, I understand that question, but 22 that is not really in my field. I would know people 23 around the country to whom I could refer who do know 24 the answer to that question and who are specialists 25 in it. BFG08079 68 Dr. Epstein - Cross 1 Now, my question to you was, you consider 2 that because you told me you considered it. 3 Now, secondly, my question was, did 4 you come up with the name of anybody in all this mass 6 of people you know who you knew was a teratologist who 8 you could expect to give the kind of testimony you 7 are giving here? 8A X repeat again, X would not presume to predict 9 the nature of a testimony of another expert witness. 10 X am perfectly happy to give names of people who they 11 could go to get the data evaluated, but X reject the 12 implication in the question that one can simply address 13 a list of experts and say, ah, yes, they will testify 14 favorably on unfavorably. X reject that most emphat 15 ically, sir. 16 g. That may be unfair. Doctor. Let me put it this 17 way: Knowing the case as you knew it, did you make 18 any references to any teratologists whom they should 19 go and consult? 20 A. That is your question? 21 Q. That is my question, yes. 22 A. The* answer is yes. 23 Q. And to whom did you refer them? 24 A. X referred them to a teratologist, a Dr. Manson, 25 in the University of Cincinnati. 69 Dr. Epstein - Cross 1 Ct Anybody else? 2 A. No, 3 ft All right, sir. 4 You have been in court enough to know 5 that a witness is supposed to be sworn before he e testifies, right? 7A Correct. S ft 9A And, you weren't here. I beg your pardon? 10 ft Were you? 11 A Most certainly, sir. 12 ft My recollection was that you were not, people 13 around me said that their recollection, when I asked 14 at lunchtime, their recollection was you were not. 15 Were you? 16 A Indeed, sir, I was. 17 ft Were you in the witness stand when it happened? 18 A I was not on the witness stand. I was facing the 19 court reporter. 20 MR. GRIFFIN: Did you? 21 THE COURT REPORTER: Yes, sir, I did. 22 MR. GRIFFIN: I am sorry, that is a 23 misunderstanding. 24 THE COURT: Mr. Griffin, if it did not 25 happen it would be the first time in my courtroom. BFG08081 70 Or. Epstein - Cross 1 MR. GRIFFIN: X am sure of' it. Judge. 2 That is the reason I thought it was very unusual, but 3 that was our recollection. We probably were working 4 on something else. S THE COURT: As a matter of fact, a 6 witness does not even reach the witness stand without 7 having been sworn. That is our practice. a MR.GRIFFIN: All right, sir. 9 BY MR. GRIFFIN: 10 Q Now, Doctor, let's get to the substance of the 11 opinion. 12 As a scientist, can I -- is it fair 13 to say that if you are trying to prove or give a 14 scientific opinion that there is a cause-and-effect 15 relationship between exposure to a substance and an 16 end result in man, you have to go through at least 17 some steps of the reasoning process. 18 A Certainly. 19 Q. Is it fair to say that you should say to yourself, 20 I have a substance which in my best judgment is 21 teratogenic in man; that is one step, because if the 22 substance was not teratogenic in man that would be the 23 end of your search right then, wouldn't it? 24 A With due respect, sir, I have to disagree. The 25 first question you ask yourself is, is there any BFG08082 71 Dr. Epstein Cross 1 evidence that the agent is teratogenic, not necessarily 2 in man. 3 Qi No. That was part of the process I was going 4 to go through. 5 A. I beg your pardon. 6& You have to find in course, in your own judgment 7 that the substance is teratogenic in man. 8 A. No, sir. 9 Ql Well, you have to get there soon or later, don't 10 you? 11 A. No, sir. May X attempt, with due respect, to 13 explain the process. 13 The process is essentially to analyze 14 the experimental data on the teratogenicity and see IS whether indeed this supports the inference that there 16 was a substantial probability that the material is 17 teratogenic in animals, or if the material is terato 18 genic in animals. That is point one. 19 On the basis of that, one makes the 30 reasoned presumption on the basis of which all toxicolog 21 is based, that one can extrapolate from the animal to 22 to the human. So, the point of fact relates to the 23 findings of teratogenicity in animals. Prom that. 24 one makes the reasoned presumption of a likely 25 teratogenic hazard in humans. That is the process. i i ' i BFG08083 72 Dr. Epstein - Cross 1 Q. I was really going to go through that process 2 in arriving at the fact that before you can complete 3 your chain of reasoning you have to have established 4 that the substance is teratogenic in man. 5 A. No, sir. There was a strong probability that 6 it is teratogenic. 7 Q. Well, that's -- 8 A. I have not made the statement it is teratogenic 9 in man. I have made the statement, I believe this 10 morning, that there was a strong probability that it 11 is teratogenic, which, sir, with due respect, is 12 different than what you quoted me on. 13 Cl That is different from saying it is. 14 A. Precisely. IS Ql You are saying in the scientific world that's 16 different. 17 A. I am stating in any world it is. I do not wish 18 to be misquoted. 19 Qi Suppose I say that as far as we lay people are 20 converned, if there is a strong probability that it is 21 we would accept that as saying well, if there is a 22 strong probability, it probably is; fair enough? 23 A. That is your inference, sir. 24 Q. Well, you -- you nevertheless -- I will put it 25 on the negative. If your scientific knowledge convinc BFG08084 73 Dr. Epstein - Cross 1 you that a certain substance was not teratogenic in 2 man, you would cease your search right then, wouldn't 3 you? 4 A. That is -- I am afraid I can't -- Z would like 5 to answer the question simply, and please don't think e 1 am being evasive if 1 don't answer the question 7 simply, but I am just unable to do so. B To say that a substance is not teratogen: 9 in man would imply the following: That it had been TO extensively tested in a wide-range of animal tests, 11 and that in none of these tests was there any evidence 12 of teratogenicity. That is point one. 13 Point two would be that there had been 14 major human epidemiological studies covering hundreds IS of thousands of women, many many thousands of women 16 who had been exposed to the agent for very prolonged 17 periods of time, in different doses under different 18 conditions, bearing in mind the possibility of a wide- 19 range of confounding variables in the absence of 20 effect. And then, all one would say is that there was 21 no evidence that it is teratogenic. One would not say 22 it is not teratogenic. Science has offered too many 23 examples to the contrary of people assuming that the 24 absence of data can be equated with safety. 25 Q. Now, if you were a student of mine I would give yo\ BFG08085 74 Dr, Ep'stein Cross I a zero on that answer. 2A Fortunately, I am not, 3 Ql My question was, if you were convinced as a 4 scientist that a subject was not teratogenic in man, 5 at that point your search would cease? that is what 6 I asked you. 7 A I have already answered that I cannot give a 8 simple yes or no for the reasons I would be willing -- 9 Q. All you are doing -- 10 A I"would be willing to say that there was no 11 evidence that it is teratogenic. I would not say that 12 it is not teratogenic. 13 Ql But, that isn't what I said. Doctor. Listen 14 to my question. Just listen to it. 15 If as a scientist you are convinced that 16 a subject -- that a substance is not teratogenic in 17 man, you would cease your further search of trying to 18 prove a cause-and-effect relationship, 19 A I would not presume that the absence of data 20 would allow me to say that it is not teratogenic. 21 I would say there is no evidence that it is teratogenic, 22 which is an important scientific distinction, which I 23 keep on coming to. 24 There was a major difference between 25 saying that a material does not produce birth defects BFG08086 75 Dr. Epstein - Cross 1 and saying there is no evidence that it produces 2 birth defects. This is a fundamental issue in 3 toxicology. 4 ft I was not saying whether it does or doesn't. 1 S was just saying, if you were convinced as a scientist S that it didn't. If the best of your scientific knowl 7 edge and the best of your scientific judgment/ and the B best of all the tests that you did week after week 9 convinced you -- you, not the scientific world -- 10 but, convinced you, that this is substance was not 11 teratogenic in man, once you got to that point you 12 wouldn't go any further in your attempt to prove a 13 cause-and-effeet relationship, would you? 14 A. I don't how -- 15 THE COURT: May I interrupt, please? 16 THE WITNESS: I beg your pardon. 17 THE COURT: Dr. Epstein, is there any 18 substance of which you are aware that you can say 19 positively is not teratogenic? 20 THE WITNESS: (Pause) I think the 21 overwhelming majority of substances are probably non- 22 teratogenic. The vast, vast majority of agents are 23 probably non-teratogenic. But, that does not allow me 24 to say that a substance is non-teratog eiic until and 25 in fact there is an overabundant extensive evidence, BFG08087 76 Dr. Epstein - Cross 1 teratological evidence in animals, and epidemiological 2 evidence in humans. 3 THE COURT: Mr. Griffin, what I understand 4 him to be saying is that even the freshest of what we S know as fresh air he would not state positively is 6 not teratogenic. That being the case, then Z think we 7 can no longer pursue your line of questioning. He 8 refuses to accept the major premise. 9 BY MR. GRIFFIN: 10 ft All right, sir. If you are going to -- if you 11 are going to prove a cause-and-effeet relationship, 12 you are going to have to satisfy yourself as a 13 scientist that there at least was enough of an 14 exposure to this substance to have caused a teratogenic IS effect. 16 A Correct, sir. 17 ft And that means you have to know or at least have 18 a reasonable scientific basis for knowing what 19 level of exposure is necessary in order to create such 20 an effect. 21 A The information which I personally would need 22 would be the qualitative evidence of exposure; the 23 fact that she was exposed. 24 The quantitative aspects of the exposure 25 I did not consider myself competent to calculate, and BFG08088 77 Dr. Epstein - Cross 1 for this reason, at a very early stage I recommended * 2 that an industrial hygienist be brought in to produce 3 estimations of the likely levels of exposure. 4 I should point out also that when it S comes to areas of teratogenesis and carcinogenesis, 6 there is a consensus in the informed independent 7 scientific community that there is no way of setting 8 safe levels or thresholds. So, any exposure to a 9 teratogen is hazardous, can produce birth defects; the 10 greater the exposure and the more prolonged exposure, 11 the greater the risk. 12 Therefore, the two points are: One, 13 I was satisfied qualitatively about the exposure; 14 there was exposure. But, B, I felt as indeed you 15 felt, sir, that it would be helpful to have the opinion 16 of a qualified expert in this area on the levels and 17 persistence over and above what I have read myself. 18 And, that was, I believe, -- that was the area which 19 X believe Mr. Todd had discussed with you and your 20 colleagues in the court. 21 0- Well, are you telling me. Doctor, that as a doctor 22 and as someone somewhat interested in teratology, 23 you can't go the other way? In other words, you can't 24 say, I won't have an opinion that any substance can 2S cause a thing of this sort unless you show me a BFG08089 78 Dr. Epstein - Cross 1 reasonable exposure; I've got*to see a reasonable 2 exposure first? 3 A. Well, sir, you have to understand what reasonable 4 exposure means. Let me, if I may, give you an example. S You would have probably imagined that 6 a part per million in air is very low, or part per 7 billion is very low, or part per trillion is very low. 8 One would probably say, well, ah hah, that is not 9 reasonable exposure . 10 Let me point out to you that we have 11 data on teratogenicity and fetotoxicity of agents 12 at the parts per trillion level. The dioxin agent, 13 the dioxin contaminant in 245T can produce defects 14 at the part per trillion level. Therefore, I do not 15 know what reasonable exposure is. 16 All I subscribe to is the opinion that 17 there is no way of setting safe levels of exposure to 18 agents causing birth defects. 19 Therefore, for that reason, I was 20 interested in this from the -- in this exposure, from 21 a qualitative standpoint. Was she or was she not 22 exposed to Diazinon? 23 If she was exposed, fine. Then the ' 24 problem begins. 25 The question statistically in a large T* BFG08090 79 Dr. Epstein - Cross 1 group of people, let us say you have 10,000 people 2 exposed to Diazinon, the frequency of birth defects 3 in that population, if they were all pregnant, would 4 be influenced by the amount of exposure and by the 5 duration. So, the longer the exposure the higher 6 the exposure, the greater would be the frequency of 7 birth defects in that population. 3 But, when it comes to any one individual 9 you can't say. You can't really give an answer. And, 10 for this reason I limited my interest in this to the 11 qualitative aspects knowing full well that the quanti 12 tative aspects of the precise levels would be dealt 13 with by those who are more qualified. 14 Q. Do I understand you to say that if there is a 15 molecule, a molecule somewhere which is breathed by 16 a person, that is enough for you? 17 A No, sir, that is not what 1 said. 18 Qt Well, then, you have to have some -- 19 A Let me explain again what I said. 20 What I said, it is the consensus of 21 opinion in the informed scientific community that we 22 know of no way of setting safe levels or thresholds 23 for agents to induce cancer, birth defects, or genetic 24 abnormalities. 25 As you talk about one molecule, let me BFG08091 80 Dr. Epstein - Cross 1 explain what one part per trillion of dioxin is. 2 One part per trillion of dioxin -- 3 ft Doctor, I am not -- 4 A. Excuse me. I would like to explain this, if I S may. 6 THE COURT: Dr. Epstein, he is asking 7 you about Diazinon. Are you willing to make the 8 statement, the same statement for Diazinon: One part 9 per trillion of Diazinon would be sufficient? That is 10 what Mr. Griffin was asking you a moment ago. 11 THE WITNESS: I understand, sir. 12 I am unwilling -- I share the opinion 13 that we don't know of any way of setting safe levels 14 or thresholds for Diazinon for exposure to any teratogei 18 including -- 16 THE COURT: Therefore, that would include 17 one molecule. 18 THE WITNESS: I think the chance is 19 that would be extraordinarily remote. But, we are 20 dealing with billions and quadrillions and trillions 21 of molecules. A part per trillion of Diazinon is 22 probably somewhere in the region of quadrillions; 23 not millions, not billions, not trillions, but quad 24 rillions of molecules. So, a part per trillion 25 of Diazinon -- and, if you want the paper calculations. BFG08092 81 Dr. Epstein - Cross 1 these can be done for you -- one part per trillion of 2 Diazinon is not one molecule, it is not a million mole 3 cules, it is not a billion molecules, it is not a 4 trillion. It is more than a quadrillion molecules, 5 and that is the ball park, if you like, we can frame 6 this discussion. 7 BY MR. GRIFFIN: 8& Well, let me go back to your deposition when you 9 were being deposed upon the levels you were talking 10 about in order to give your opinion at that time. 11 A. Yes. 13 Now, you say here, among other things, on page 13 69, "So, we are dealing with exposures that were not 14 trivial, and if you want to follow my line of 15 reasoning that the dosage required to produce minimum 16 symptoms is in the region of 50 to 80 milligram." 17 And, that is over -- "And, there are 18 references to support that. There is documentation 19 to support that. That's equivalent, say, to a 20 milligram per kg body dose." 21 Now, when you are talking about a 22 milligram per kg body dose, you are talking about 23 one milligram per what? 24 A A kilogram of what he weighed. 25 Q. Right. And, translated into something like the BFG08093 82 Dr. Epstein - Cross 1 TLV, the Threshold Limit Values/ what does that mean? 2 A. I really couldn't do an off-the-cuff translation, 3 but it is very much in excess of that, 4 ft "This was going on repeatedly. It is not just 5 one occasion an element like Diazinon, although it 6 isn't very stable and persistent material. We do enough 7 of it staying around after a spraying to make people 8 sick when they returned." You knew that, didn't you? 9 A. What is your question? 10 ft That was a premise for your opinion in those 11 days, wasn't it, that there was an exposure of such 12 an extent that it caused people to get sick when they 13 came back the next day? 14 A. Well, certainly. What you have read is several 15 things, and I am not certain if you want a yes or no 16 from me or you want me to comment on any part, 17 ft Well, that is what you testified to before, isn't 18 it? 19 A. Yes, I certainly did testify to that, 20 ft All right. 21 Then, "Well, is your basis for believing 22 that there were incidents like that earlier in her 23 pregnancy?" And you said, "Well, I am told again that 24 there were multiple exposures to Diazinon in the first 25 trimester. The dates, I have a couple of them." BFG08094 83-84 Dr. Epstein - Cross 1 Now, by multiple exposures, did you 2 mean exposures of the kind that made people sick when 3 they came back the next day? 4 A. By multiple exposures I meant exposures which wwerc 5 more than one. e& And, by exposure you mean exposure to more than 7 one molecule? 8A Well, we didn't discuss the number of molecules 9 there, but I have already indicated to you that we 10 are dealing, if you want to translate this into mole 11 cules, you are dealing in the very, very high orders 12 of magnitude in terms of more than quadrillions. 13 & Just dealing in terms of human experience, what 14 is the experience to your knowledge of people coming IS in contact with molecules of Diazinon day in and day 18 out, everywhere they go? 17 A I am not clear what the question is. Is it relatin 18 to birth defects, what is it relating to? 19 Cl I am just talking about people's exposure to that 20 particular chemical. Are people exposed to it a lot 21 or aren't they? 22 A Weli, certainly people who formulate and manufactur 23 the material do have fairly constant exposure and people 24 2S n Have you ever heard -- BFG08095 85 Dr. Epstein - cross 1 A. Excuse me. 2 Q. One at a time. If you will just tell me the 3 people who are exposed, I will ask you after each 4 one. 6 A. Please let me finish. 6& 7 Have you ever -- THE COURT: Hr. Griffin, let him finish a his answer. 9 You do pretty well asking questions. 10 Give him a chance to answer. 11 A. What I was going to say was that people who 12 tend to have sustained exposure would fall into several 13 categories. First of all, manufacturers and then 14 formulators and then applicators; in other words, IS people who actually manufacture the material, people 16 who take the material once it is manufactured, make 17 it up into solutions or preparations which pesticide IS applicators cna then use; and then the third are 19 pesticide applicators, people who actually apply the 20 material in homes or buildings or for agricultural 21 purposes. Those are really the three major categories 22 of people that have sustained exposure. 23 I am unaware of the likelihood that 24 pregnant women would fall -- would be occupied or 25 employed in those three categories, but I can't exclude BFG08096 86. Dr. Epstein - Cross 1 that possibility. 2 Qt Well, you would assume, don't you, that there are 3 some pregnant women who do gardening. 4 A. There is nothing I have said which would lead you 5 to a contrary assumption. 6 Q. And would you think that some of them would use 7 Diazinon? It is a very common insecticide, isn't it? 8 A. 9 Q. I would not be willing to exclude that possibility. And, in using Diazinon they become exposed to it 10 in one degree or another. 11 A. Possibly. Certainly. 12 Q. As far as experience is concerned, do you know of 13 any case in the entire world where somebody, because 14 of being exposed to Diazinon had a teratogenic effect? IS A I have no idea of this. Largely, because the 16 vast majority of birth defects -- and, I can tell you 17 that the incidence of birth defects is not trivial. In 18 the vast majority of incidences of birth defects there 19 have been neither investigation nor inquiry into . 20 possible causes. And, in fact, to produce an answer 21 to your question, one would have to have a very long -- 22 large-scale epidemiological study with a large number 23 of women exposed to be able to develop such inferences 24 of the kind you are inquiring about. 25 Cl There seems to me that there is a fundamental v. BFG08097 87 Dr. Epstein * Cross 1 difference here between us. 2 In the courtroom, you know, what we 3 are trying to prove is the fact, right; the fact, not 4 the question of what might be or what could be, and, 5 to the extent, as I see it, to the extent that science 6 has not yet given us an answer, to the extent that we 7 are still in the realm of that's the world and that's 8 God, and that all those things we don't have answers 9 for, we say they are not provable. Do you think 10 differently from that? 11 A. Yes, sir, sir, I think I understand what you are 12 driving at. The situation here is, we know that this 13 lady, during her pregnancy was exposed to a pesticide 14 for which the substantial preponderant evidence in the 15 literature demonstrates that it is teratogenic, period. 16 Therefore -- 17 & Wait a minute. Teratogenic in where? 18 K Would you please not interrupt my answers and 19 then I think we can proceed more expeditiously. 20 -- was teratogenic in a series of 21 experimental animal systems. And, on the basis of this, 22 this offers, this presumes a potential human teratogenic 23 hazard because of the preponderance of evidence in the 24 literature there is a presumption this agent is also 25 teratogenic in women. BFG08098 88 Dr. Epstein - Cross 1 We also have some evidence of persistence 2 of these materials, we also have evidence that there 3 was an exposure roundabout the time of the critical 4 time of the formation of the palate and lip. In 5 addition to this, there was no other known -- she was 6 exposed to no other known teratogens and there were 7 no other known predisposing factors. B If you want to talk about the science, 9 that is the science. 10 0. Now, let me go back. I was talking to you about 11 exposure, and whether you knew of any cases of exposure 12 in the world, and you said the answer is, you do not 13 know. And so, it leaves, as far as the epidemiological 14 world, as far as science knows it, they know of no 15 connection, epidemiologically -- for the jury, you 16 better tell the jury what epidemiologically means. 17 A Let me attempt to answer. The answer is no, 18 I know of no evidence. Now, let me point out something, 19 ft First tell the jury -- 20 A I have already given my answer. The answer is 21 no, but let me explain what epidemiology is, and then 22 let me explain -23 THE COURT; Excuse me. Doctor. You did 24 receive what amounted to an invitation from Mr. Griffin 25 to deliver a lecture. BFG08099 89 Dr. Epstein - Cross 1 X think really what it called for thoug] 2 was a short definition of epidemiology. And, I would 3 request that you answer the questions that are posed 4 to you. There is a danger in delivering lectures. S THE WITNESS; All right, sir. 6 Epidemiology is basically the study of 7 adverse effects in human populations. In other words, 8 what evidence is there in human beings of cancer or 9 birth defects. Are these related to ethnic factors, 10 to race, to religion, sex, exposure to various chemical; 11 in the environment. And, one of the problems about 12 epidemiology is, like toxicology, it is very insensitive 13 And let me explain this. 14 To develop inferences -- 15 ft Doctor -- 16 THE COURT: I think we passed the 17 definition sometime ago. All right. 18 Mr. Griffin, please, please avoid the 19 lecture soliciting-type of questions. Now, make them 20 precise. 21 MR. GRIFFIN: It is difficult, 22 ft Am I not correct that as far as epidemiology is 23 concerned, there is no demonstrated connection between 24 Dia2inon and human experience? 25 A The absence of data in no way implies safety. BFG08100 90 Dr. Epstein - Cross I You have to do very extensive* studies with large numbers 2 of people over long periods of time before you can 1 3 develop such evidence. For tobacco alone, where 4 millions of people were exposed to tobacco, and smoked i 5 for years, for several decades it took four decades of j 6 research before relationships of tobacco and lung cancel 7 could be established. Nowadays, the relationship 8 between tobacco and lung cancer is clearly accepted, 9 but it took millions of people. Bow many millions of 10 pregnant women are being exposed to Diazinon at differed 11 doses on a routine basis so we can develop information 12 of of the kind you seek? The answer is -- 13 TBS COURT: Excuse me. Dr. Epstein, 14 perhaps that would have been an answer to the question, 15 is there positive proof that there is no connection. 16 Perhaps that would have been the answer to the question 17 I think Mr. Griffin asked you, and I 18 will ask the reporter to check this, is whether there 19 is any epidemiological study that does connect the two; 20 not whether there is anything that does not connect or 21 proves that there is - 22 THE WITNESS: Thank you, sir. 23 I am unaware of any published epidemio24 logical data in the literature of the teratogenicity of 2S Diazinon and therefore you can't answer yea or nay. BFG08101 91 Dr. Epstein Cross 1 BY MR. GRIFFIN: 2 ft In other words, as far as you know, no scientist 3 had ever tried to study a cause-and-effect relationship 4 between those two things? 5 A. Ciba has not funded such a study or published the 6 results of such a study, that i s correct. 7 Qi You don't know of any such study, do you? 8 A. Ciba has not published -- 9 MR. GRIFFIN: Judge -- 10 TBS COURT: Excuse me. No, no, no. 11 Dr. Epstein, this is not a question of whether Ciba 12 did anything. He is asking you whether any scientist 13 14 A. No, sir, there is no published data to my knowledge IB There may well be data in Ciba'a unpublished files, 16 but there is no published data in the literature 17 to the best of my knowledge, with two exceptions. 18 Now, these two exceptions are interestin 19 Do I have permission to refer to them, 20 sir, as I have not referred to them at the time of 21 my deposition? 22 THE COURT: I am not sure which are 23 the questions anymore and which are the answers. 24 Now, Mr. Griffin, if you will ask a 2S question so that we can proceed. BFG08102 92 Dr. Epstein - Cross 1 ft I will go back to exposure. 2 On page 72 of your deposition, did you 3 not testify: "If she wasn't exposed at all, clearly 4 my professional interest in the case would cease 5 immediately. The calculation which I offer was simply 6 illustrative of the kind of ball park dose level, the 7 very high ball park dose level which she could have a gotten.* o A. Correct, sir, 10 ft Do you still consider a level of, say, 1/4 to 11 1/Sth of the TLV a very high dose level? 12 A. Well, you will have to explain what you mean by 13 that.. For what period of time, what period of gestation 14 ft Well, I am talking, less than an hour of exposure. 15 A. You are absolutely right, that certainly the 16 shorter the duration of the exposure and the lower the 17 level of the exposure, the lower the risk. The longer 18 the level of the exposure and the higher the amount to 19 which you are exposed, the greater the risk. But, with 20 TLV's, with due respect, are totally irrelevant in this 21 connection. TLV's are standards based largely on acute 22 and subacute short-term toxicity. TLV's don't reflect 23 teratogenicity. 24 ft Well, Doctor, the best you can do is the best you 25 have. What, instead -- suppose I was a fellow who is BFG08103 93 Dr. Epstein - Cross 1 trying to set a level. Suppose I had the problem, I 2 am in a business and I have a problem with women who 3 work in my business and I don't want to exposre them 4 to anything that is dangerous and I want to know the 5 level for the pregnant women in my business. Row, where 6 do I find it? Do I find it in charts somewhere that 7 tells me? 8 A. Good question. Good question. Now, let me try 9 to respond. 10 Let me first of all make it clear what 11 a TLV is. A TLV is a Threshold Limit Value which was 12 set non-governmental groups originally known as the 13 American Conference of Governmental, Industrial 14 Hygienist -- actually they were governmental, but they 15 were acting independently -- who reviewed the toxicity 16 data on compounds and produced standards allowing -17 governing allowable exposure in relation to acute and 18 subacute toxicity. In other words, if somebody would 19 drop down dead either today or would be -- within 20 two or three weeks. None of these reflected long-term 21 effects like cancer or birth defects. So, TLV's, again 22 with due respect, are totally an absolutely irrelevant 23 to the question of teratogenesis, with one exception, 24 and this is an exception in which again I was involved 25 in the formulation of these standards in the workplace; BFG08104 94 Dr. Epstein - Cross 1 namely, with lead. When it came to lead, we attempted 2 to introduce -- 3 Ql (Mr. Griffin whistling.) 4 A. -- introduce the area of birth defects -- 5 Qi Doctor -- 6 A. -- into the TLV. With the exception of that, 7 TLV's are irrelevant. 8 THE COURT: Dr. Epstein, the question 9 started out, Mr. Griffin wanted to know if he were 10 in this particular business and he wanted to know what 11 would be a safe level for pregnant women who worked in 12 his business, could you give him an answer? 13 THE WITNESS: Yes, sir. 14 THE COURT: And, he didn't ask you about 16 TLV. He is asking you the Epstein safe level for work. 16 Can you give it to him? 17 THE WITNESS: The safe level for work 18 in which I would ascribe, and all of the members of 18 the independent and informed scientific community and 20 government regulations is that we don't know of any way 21 of setting safe levels for agents that induce cancer 22 birth defects or genetic abnormalities. Therefore, 23 you do not employ pregnant women under conditions under 24 which they can be exposed to teratogenic agents, period 25 We -- for instance, we now have data BFG08105 95 Or. Epstein - Cross 1 that even a few glasses of alcohol in an early stage 2 of pregnancy can produce fetal alcohol syndrome. Now, 3 how much is enough? We don*t know the answers to this. 4 For this reason, as the NXOSH document S states, do not -- handle with caution by women of 6 childbearing age. You do not take women who are 7 pregnant or who are presumed to be pregnant and allow 8 them to be exposed to agents which cause birth defects, 9 period. That is the answer. There is no Epstein figure 10 there is no National Cancer Institute figure, there is 11 no government figure except we don't know of any way 12 of getting safe levels for exposures to agents producing 13 birth defects. 14 Ql All right. I suppose it is fair to say you don't IB have any governmental agency that agrees with that one, 16 do you? 17 A. Most certainly. This is the position on inability 18 to establish safe levels for carcinogens, mutagens and 19 teratogens is a commonplace position. A very common 20 place position. 21 Q. Where does it appear? Where is there any govern 22 mental regulation which says, if there is -- when you 23 used the word teratogen, incidentally, you are talking 24 about a substance which has been shown to be teratogenic 25 in a species, in an animal. You are not using it in BFG08106 96 Dr. Epstein - Cross 1 man, are you, because you don't know whether it is 2 teratogenic in man or not. 3 A. That's correct. We are talking about a presumed 4 teratogenic hazard. 5 ft As I gather from what you say, your guide would 6 be, if there is ever a demonstration of a teratogenic 7 effect in an animal, then you don't hire pregnant peopl 8 A 9 Yes. Let me respond to that. The first time in which this was 10 enunciated and enunciated very clearly in relation to 11 exposure of pregnant women, was in perhaps in the leadi 12 government report on this matter, namely, the MRAC 13 Commission of 1969. That is Secretary Finch's commissi 14 on pesticides and their relationship to environmental IS health, which clearly and explicitly and unambiguously 16 stated that the use of pesticides to which -- which 17 had been shown to be teratogenic, that use should be 18 restricted to prevent exposure of pregnant women. This 18 is a clear and unequivocal statement to HEW Secretary 20 by an expert panel, 21 ft And was it adopted? 22 A There has been, certainly -- 23 ft Does the government agree with it, that's what 24 I want to know. 2S A Let me just point out that until very recently BFG08107 97 Dr. Epstein - Cross 1 it is only in the last two or' three years that the 2 question of reproductive hazards in the workplace, 3 sterility in men, birth defects in women, it it only 4 very recently that this has become a subject for 5 concern. 6 There are, to my knowledge, no OSHA 7 regulations as yet, governing the specifics of a teratogenic exposure. 9 What I was discussing was the opinion 10 in the scientific community that we don't know of any 11 way of setting safe levels. 12 And, furthermore, you asked me what my 13 recommendation would be, and my recommendation would 14 be the same basically as that of the NIOSH, thatyou 15 don't expose pregnant women to materials that can 16 produce birth defects. 17 ft Now, listen to this question. I don't want Dr. 18 Epstein's opinion.. I simply want a volume somewhere IS that has a standard in it. Is there one? 20 A When I offer you data in the literature, you say 21 I can't quote this because I didn't discuss it with 22 you at the time of the deposition. I have given you 23 repeated statements from the literature, Government 24 scientists and others on the teratogenicity of Diazinon. 25 You have sought to exclude this on the ground that I BFG08108 98 Dr. Epstein - Cross 1 did not discuss this at that time of the deposition. 2 Now you are putting me in a difficult position now 3 because if I refer to this again 1 risk being in 4 contempt of court. S THE COORT: You are relieved from that 6 if you can point out anything in the literature that 7 sets forth the standards in answer to Hr. Griffin's 8 question. 9 A. I am unaware of any governmental standards on 10 birth defects. These were under consideration at the 11 time of the Carter Administration but have not been 12 promulgated in this present Administration. 13 Q. NOW -- 14 A. ' That is in relation to occupational exposure. 15 THE COORT: Mr. Griffin, let me 16 interrupt for a moment. 17 Counsel at counsel table are cautioned 18 to make no facial expressions whatsoever. 19 A I beg your pardon. In relation, say, to consumer 20 products in drugs, the FDA, I think, takes very clear 21 and unequivocal action on this. And, let me just 22 very briefly state what this was. 23 Subsequent to the thalidomide episode- 24 I1R. GRIFFIN: Your Honor, please. 25 A You asked me -- BFG08109 99 Dr. Epstein - Cross 1 MR. GRIFFIN: Your Honor, drugs and 2 the FDA, I think we are just getting beyond our ken. 3 THE COURT: We are dealing here with the 4 question of the effects of Diazinon. Let's move on. 5 The next question, Mr. Griffin- 8 ft Now, is it correct. Doctor, that in 65 to 70 percer 7 of all cases of developmental defects in man, that the B cause is unknown, flat out unknown? 9 A. 1 think that is fair to say that, yes. i 10 ft Talking again about man, what substances are there 11 that have been shown of all the different substances 12 we have, what substances are there that have been 13 shown to be teratogenic in man as differentiated as 14 being teratogenic in animals? IS A. Do you mean -- when you say, as opposed to, do 16 you mean when the animal data are negative? 17 Q. No. I mean -- forget all animal studies. I am IS just asking about what has been shown to the extent of 19 present day knowledge of the scientific community, 20 what substances are teratogenic in man. 21 A Okay. Well, the causes of birth defects -- 22 & What substances are teratogenic in man? 23 A. Okay, fine. 24 Well, substances fall into various 25 categories. First of all, infectious, like German BFG08110 100 Or. Epstein - Cross 1 measles. Is that responsive to your question? 2 Q. It is ambiguous. I wouldn't have thought of it 3 as a substance, but if you do -- 4 A. May X simply answer your question in relation to 5 the risk factors or predisposing factors of birth defect : 6 which would allow me to make reference to infectious 7 agents which aren't in your understanding substances, 8 okay? 9& Okay. 10 A. Fine. So -- well, the first is, I suppose, 11 genetic and familial predisposition, which is one 12 factor. That is important. There is a genetic and 13 familial predisposition. 14 There are ethnic factors. For instance, IS Orientals have a higher incidence of birth defects, 16 Particularly in cleft lip and cleft palate than non- 17 Orientals. 18 The maternal x-rays, radiation, which 19 isn't a substance, but is an influence, an adverse 20 Influence, and maternal radiation is an important cause; 21 infectious agents, like rubella, German measles? drugs, 22 a series of drugs have been shown to induce birth *23 defects, such as thalidomide, which we have repeated, 24 meclizine, a drug used in the treatment of morning 2S sickness? Aminopterin, a folic acid antimetabolite; BFG08111 101 Dr. Epstein - Cross 1 anticonvulsant drugs, drugs used in the treatment of 2 maternal epilepsy? then a series of toxic chemicals, 3 particularly methyl chemicals like methylmercury, and 4 then this may not be totally responsive, but there is 5 an interplay of these factors, what we call multi- 6 factorial influence; that is, the interaction of 7 exogenous factors, such as infection, or chemicals, or 8 what have you; and, genetic susceptibility. 9 In other words, it is possible that some 10 people have a built-in genetic susceptibility. That 11 coupled with the environmental exposure, whether it be 12 a drug or pesticide, or what have you, the two of 13 them are important. 14 So, I think we have to bear in mind, IS in addition to the exclusive external factors, and 16 interplay with internal factors or genetic predisposi 17 tions. That is just an off-the-cuff listing. 18 Ql But still, if you have a birth defect, and if you 19 take into account all the things you know which may 20 cause it, you still end up with 65 to 70 percent of 21 them that you just can't attribute anything to. 22 ft. It is not you can't, sir. I wish that was the 23 case. Unfortunately, the overwhelming majority of 24 birth defects haven't been studied. We don't even, 2S in this country, have a birth defect registry. BFG08112 102 Dr. Epstein - Cross 1 I am consultant on birth defects* on 2 cause of birth defects to the March of Dimes. One 3 of the things we are trying to do is set up a national 4 registry. Sweden has a national registry. We don't 5 have one in this country. e So, we don't have the baseline data 7 on human birth defects. But, -- even, for instance -- 8& But -- 9 A. Excuse me, just one second. The occupation, 10 maternal and paternal occupation is not listed on 11 birth certificates in this country. One of the things 12 we have been trying to do just to answer your kind of 13 question as to what maternal influences possibly could 14 have had an effect on the birth defect, we don't have 15 the information. But, it doesn't mean to say the 16 influences, the environmental influences aren't there. 17 You must not equate the absence of data with the absence 18 of a causal association. 19 & But, it doesn't mean that they are there either. 20 A. 1 couldn't agree with you more. 21 Qi It doesn't mean one way or the other. You just 22 don't know. 23 A. That's right. 24 Q, And, in 65 percent to 70 percent of the cases, 25 based on the present scientific knowledge, you don't BFG08113 103 Dr. Epstein - Cross 1 know what it is. 2 A. Not based on the scientific knowledge/ because 3 nobody has really looked. It is an absence of data. 4 Q. Then/ based on our knowledge as human beings, we S don't know. 6 A. 7 Based on the absence of data. Mr. Griffin, if you will 8 simply revise your question, based upon lack of knowled< 9 then. Perhaps you will accept that. 10 & There is not adequate knowledge. tl A. There is a lack of knowledge. There's almost an 12 absence of it. 13 Q. Now, for the purposes of our discussion from here 14 on in, would you take the words "lack of knowledge," 15 and "no*, as the same thing? 16 A. No, I most certainly would not be prepared to do 17 that, sir, with due respect. 18 Ql If, as a scientist, you don't know the answer to 19 something, for the purposes of proof, can't you accept 20 the proposition that it can't be proved? 21 A. Most certainly not, and let me explain why. 22 In the majority of instances of consumer 23 product safety, pesticides, there is a massive lack of 24 information in the published scientific literature. 25 However, there is a great deal of information in indust: BFG08114 104 Dr. Epstein - Cross 1 files which industry has resisted making available for 2 scientific inquiry and exposure. 3 Now, is one to say that because there 4 is no data in the open published scientific literature 5 there is no hazard, when knowing full well that there 6 may be very extensive data in industry files. And, I 7 have had extensive experience as a government witness 8 looking into industry files for data which have never 9 been published in the open scientific literature. ID So, are you putting me in a position 11 of saying, because an article is not published in the 12 scientific literature I am to assume that it doesn't 13 represent a hazard from cancer or birth defects when 14 a firm, or industry, may have data stacked to the ceiling 15 on the ability of this material, but this information 16 has never been made available to the public. 17 Ql I don't recall asking you anything about literature. 18 A Yes, you most certainly did. You talked about the 19 absence of information. The absence of information cannot 20 be equated with safety, sir. 21 Ql Doctor, the absence of information to me means 1 22 absence of information. If we have the information, 23 wherever you say it may be, if we have it, then you are 24 going to know. 25 A. You are asking me to equate this with no effect. BFG08115 105 Dr. Epstein ~ Cross 1 That is the hangup, sir. 2 ft If we don't know, if it doesn't come into this 3 courtroom today, as far as this courtroom is concerned, 4 we are not going to know, correct? 5 A. No. For instance, if you have information in 6 your files which you refuse to make available, or if 7 you refuse to allow me to refer to information which 8 I have in my files, that is not the same as saying 9 there is not effect. 10 ft Hell, I think you have to accept for the purposes 11 of our procedures, Doctor, that it is the same effect, 12 and you have to -- 13 A. Net in my book, sir. 14 THE COURT: Doctor, you will have to 15 operate according to our book. 16 ft You have to understand our process, Doctor, or 17 we never can get anywhere. And, our process is to 18 simply take the evidence that is before the Court and 19 to weigh the evidence that is before the Court. 20 You aren't the weigher. You are here 21 to give us some evidence that is helpful if you've got 22 it, and i am trying to find out what there is in the 23 way of evidence on a question really where is the 24 evidence? not are there suppositions, not are there 25 possibilities. Finding out what it is. BFG08116 106 Dr. Epstein - Cross 1 HR. BOLDEN: Your Honor, I have an 2 objection. The objection is this: What Mr. Griffin 3 has asked Dr. Epstein to do is accept the proposition 4 that from here on in -- and we don't know what from 5 here on in is going to be -- that lack of knowledge 6 means no knowledge. 1 think that what he ought to do 7 is ask his questions one at a time and then perhaps 8 Dr. Epstein can answer each specific question. But, 9 to ask him to give a broad-premised statement and 10 agree to it, I think is unfair. 11 THE COURT: Well, I think the question 13 started with what appeared to be a very simple proposi 13 tion; that if there is no knowledge on a particular 14 subject, one must answer, I don't know what the answer IS is. And, it was in the refusal of the witness to 16 accept that apparently simple position that we got 17 into this by-play, and it is a great deal of by-play 18 and I would request Mr. Griffin to cut it as short as 19 possible and move on to a more fruitful area of inquiry 30 MR. GRIFFIN: I will cut it right there, 21 your Honor. 23 BY MR. GRIFFIN: 23 Qi Doctor, in this area -- if we are trying to solve 24 the question is a substance teratogenic to man, we 25 don't have any epidemiological evidence on it, we go to BFG08117 107 Dr. Epstein - Cross 1 the animal studies, correct? ' 2 A. We try to look for humans first. We do look at 3 the animal data, certainly. 4 Q. Once we looked at the humans to the extent that 5 we are able to and we don't have data there, or what 6 we see doesn't give us any proof, we then go to the 7 animal studies. 8 A. Fine. 9 ql And, that is what the subject of teratology is 10 all about, isn't it? 11 A Well, it is one aspect of teratology, certainly. 12 Qi The man who is a teratologist is a man who spends 13 his life doing that process, correct? 14 A No, not necessarily. A teratologist can be a 15 bench teratologist and do experimental work; he can 16 be a clinical teratologist, he can be an epidemiological 17 teratologist, he can be a teratologist who studies 18 basic mechanisms. 19 Ql But, they are all in the process of trying to use 20 the best judgment they can in developing data from 21 animals and then extrapolating that in humans. 22 A Not in the slightest. A lot of teratologists 23 work on basic mechanisms trying to understand what are 24 the basic mechanisms involved in teratology. The whole 25 area of risk assessment is an important part of BFG08118 108 Dr. Epstein - Cross 1 teratology, but please, sir, don't equate the two. 2 They are just not equatable. 3 ft Believe me. Doctor, X may give an oversimplified 4 question to you because X don't understand the subject. 5 And, if I don't understand -- 6 A. 7 ft Well, I am trying to be helpful to you. Then, X will put it: In this process of doing B animal experimentation, there are teratologists who 9 do that, right? 10 A. Certainly. 11 Ql And then there are people who draw conclusions 12 from the experiments, and the process of trying to 13 get experimental data, and to work from the experimental 14 data as best you can, extrapolating that and saying to 15 what effect does that show it's likely the substance 16 might have on man. 17 A. Fine. Okay. IS ft And, in that area, you looked at these studies, 19 correct? 20 A. Correct. 21 ft And, in any study that youlooked at, to start 22 off with don't you have to evaluate whether the study 23 is a good scientific study? 24 A. Oh, certainly. 2S ft And so, if we were discussingwhether these various BFGQ8U9 109 Or. Epstein - Cross 1 studies really meant anything in this overall area -- 2 A. With due respect, you are looking at the wrong 3 chart. 4& Okay. whether these studies are meaningful in 5 this overall area and whether they really prove anything 6 if you go study by study, you are going to ask was 7 the study correctly conducted according to standards 8 that are not accepted in the world of teratology; that 9 is the experts who say what kind of a study ought to 10 be conducted; that is the field you are not an expert 11 in, is it? 12 A. Well, I have been involved in helping set up 13 guidelines, but as I said before, I am not a profes 14 sional teratologist. 15 Ql If somebody was going to set up all the parameters 16 of a study, you haven't really don't that yourself, havo 17 you? 18 A. Oh, indeed I have. I have been involved -- 19 Ql On teratology -- 20 A. Excuse me, would you allow me to finish? 21 Q. Yes. 1 22 A. Most certainly in the MRAC Commission I and my 23 panel created guidelines and set up and helped formulat i 24 guidelines for teratogenicity testing in animals. 25 Now, as I said before -- I don't wish to BFG08120 110 Dr. Epstein * Cross 1 be difficult or confuse you. >I am not a bench teratolo<> 2 gist in the sense that I don't spend my time everyday 3 exposing pregnant animals. But, 1 have been massively 4 involved in the interpretation and validation of data 5 and also in developing guidelines for how to handle 6 toxicologic experiments in general, also teratological 7 data -- teratological experiments. 3 CL Before you take an esperiment and would be willing 9 to rely on the results, you have to convince yourself 10 that the experiment is a sound one, is that fair enough 11 A. Yes, there is a question of judgment, I agree with 12 you. 13 ft And, -- 14 A. Yes, there is a question of judgment involved here IS clearly. 16 ft And, why is it that an experiment must be a sound 17 one? 18 A. Well, let me explain. If, for instance, you 19 have a very small number of animals and you inject or 20 administer a material to it, and you get no effect, you 21 can't, on the basis of that, say this agent is not 22 teratogenic. Therefore, if you are dealing with a very 23 insensitive test, you can't develop negative inference 24 from it. 25 However, you don't have the same set of BFG08121 111 Or. Epstein - Cross 1 equally strict concerns when you are dealing with a 2 positive effect. 3 As 1 explained this morning, there is a 4 great difference between a negative and a positive effecl. 5 One is less concerned about a small number of animals 6 when it comes to a positive effect, especially if you 7 have reasonable overall design, you have multiple doses, 8 and especially if the results of that experiment are 9 replicated or reproduced in other experiments. So, it 10 is a question of judgment. But, you are absolutely right, 11 with a small number of animals you don't allow negative 12 inferences, you don't allow somebody to say it is not 13 teratogenic. 14 With a small number of animals, however, IS you can make inferences on positive effects on teratogeni16 city, especially if the results are replicated in other 17 experiments, especially if there are multiple doses, IB and factors of this kind. So, it is a question of 19 judgment. 20 & I assume. Doctor, that what you are trying to do 21 when you say you take animals, we are going to try to 22 eliminate by the animals we have all the chance things 23 that may occur. 24 A Well, could you be just a little bit more precise 2S in your question? BFG08122 112 Or. Epstein - Cross 1 Ql Well, maybe it is not a good question. 2 A. I think I know what you are getting at, but -- 3 ft Well, what I am getting at is, animals are subject 4 to birth problems and they are subject to birth problems S the same as other people are. e A. 7 Q. Sure. And they are subject to birth problems from all 8 sorts of potential causes, and you are not sure exactly 9 what they are. And, if you just take some animals and 10 just study the animals, you are not sure if you adminis- 11 ter a substance whether it is the substance that is 12 causing the change or one of these many many other 13 extraneous factors. 14 A Right on. Absolutely. IS Ci And, you have to make sure that your animals are 16 such to the extent that science is able to do that. 17 A You are absolutely right. IS Ci And, so, part of this art in making sure you have 19 got the right strain of animals, right? 20 A Well -- 21 & That you have them protected and all that. 22 A Well, when you say the right strain of animals, I 23 wish one was gifted with design instincts for prophesy. 24 Unfortunately, we never know what the right strain of 25 animals is. All one can say is that there were BFG08123 113 Dr. Epstein - Cross 1 suggestions from the literature that in 1967 and 1968, 2 the two strains of rats got birth defects when Diazinon 3 was administered. Now, when the Ciba-Geigy 1974 study 4 was done, they selected another strain of rates. 5 Now, the question, what is the right 6 strain of rats, I don't know. But, X would suggest that 7 one way of defining the right strain of rats would be to 8 try to look at that strain of rats from which you had 9 positive data already, or suspicious data already. 10 Now, having said that, let me admit 11 that there was an argument in the literature as to 12 whether or not you should concentrate just on rodents, 13 or have mammals or have mammals other than rodents. And 14 there are some people who would suggest that over and 16 above mice and rats or rabbits, what have you, you shouli 16 have one or two nonrodent species, like a pig or a dog. 17 And here, this is what we have. 18 In addition to the rodent species of 19 two strains of rodents, you have mammalian species other 20 than rodents. You have a pig and a dog. 21 So, I don't really know what you -- the 22 answer is select the right strain. The right strain 23 is the strain in which you find positive findings, and 24 that is somewhat circular but -- 2S Qt, What was the question? BFG08124 114 Dr. Epstein * Cross 1 A. You asked me how to select the right strain. 2 Q. I didn't ask you that. x said, part of the art of 3 this business is the process of selecting the right 4 strain, isn't it. Doctor? 5 A. Well, I just told you it is difficult to select the 6 right strain. It is customary to use a couple of rodent 7 species, not necessarily to finding what the strain is. e Strain is different. And, also in the view of some, 9 you should use a nonrodent species. 10 & The scientist is trying to get a species which, if ii there is a substance applied, and if that substance is 12 teratogenic in that species it will show up, right? 13 A. Fine. 14 Ci That is one judgment you have to make. You have 16 to decide that to start with. 16 A You are really dignifying this and suggesting it is 17 more scientific than it really is. We don't really know 18 of any way. 19 Most people do teratological testing on 20 a couple of species, on a rat and a mouse, and what have 21 you, and they select very often the strain that happens 22 tobe available. 23 Your suggestion dignifies the process 24 to a higher scientific level than it generally really 25 is. BFG08125 115 Dr* Epstein - Cross 1 Qk It is a judgment call whether you are doing -- 2 Well, it is often convenience, what you happen to 3 have around in the lab. 4 fr It may be convenience and it may be a judgment call a right? 6 A. 7 Q. Fine. Fine. And, then, after you have made your selection, you 8 have to try to the best that you are able to isolate thai 9 animal from anything else happening to it. 10 A. Yes. Certainly. Essentially what you try to do is 11 to prevent your test animals from being exposed to other 12 teratogenic agents, and you also expose -- you also have 13 concomitant control animals which are not tested - whicl 14 are not exposed to the agent under test. And, one 16 reason for that is to try to contrast the difference in 16 the birth defects or the cancers between the tests and 17 the control animals, and also to take into account the IB possibility their may be some unknown environmental | 19 influence which is producing the effect which you want 20 to exclude, and that is the reason why you want to have 21 controls at the same time. 22 & And, because there are these other environmental 23 influences and there may be other things that happened I 24 to test animals, the governmental bodies that deal with 25 this have standards which they have set up as to the BFG08126 116 Dr, Epstein - Cross I number of animals you have to use. 2 A. Well, there have been various standards for this. 3 And again, as I mentioned before, I have been involved 4 in the setting of some of these standards. 5 For instance, the earlier standards 6 for pesticides were known as the FIFRA guidelines. 7 FIFRA is short for Federal Insecticide, Fungicide, 8 Rodenticide Act. This is an Act of 1947 as amended in 9 1972. The Federal Environmental Pesticide Control Act, 10 which basically gave the administrator initially of the 11 United States Department of Agriculture, and subsequently 12 the administrator of the Environmental Protection Agency 13 the right to require certain data on adverse effects of 14 pesticides prior to their registration. 15 The FIFRA guidelines had a relatively 16 small number of animals -- to be quite frank, I have 17 forgotten exactly the number of animals they recommended IS in the teratogenicity tests. 19 The Good Laboratory Practices guidelines 20 which came out later in fact recommended more animals. 21 These are fairly recent, the Good Laboratory Practices, 22 I think is about '78, or something like that. So, these 23 are relatively recent guidelines. I don't think there 24 is any question that if today you start and design a 25 teratogenicity test, you want to build in a goodly number BFG08127 117 Or. Epstein - Cross 1 of animals. But, that is different from saying, I am 2 going to disregard data on positive effects prior to the 3 development of those standards, especially if there is 4 data coming from tests, repeated tests in different 5 species and different strains, all of which have been fl positive or highly suggestive are positive. 7 The fact there are guidelines today 8 doesn't invalidate data which existed prior to the 9 development of the guidelines, especially if those data 10 were positive. 11 & Isn't it implicit in the fact that certain govern 12 mental agencies and others set guidelines, that in their 13 judgment at least, if the guidelines are not followed yo\. 14 don't have an adequate study? 15 A. Well, the object of this is to try and ensure 16 that subsequent to the passage of the guidelines, the 17 people who do these tests will do them based on the 18 cookbook recipe. That doesn't mean to say the cakes 19 baked before then were ineatable. Nor does it mean to 20 say that teratogenicity or carcinogenicity tests done 21 prior to the formation of these guidelines have to be 22 disregarded. 23 ft But, it does say, as far as present-day knowledge 24 is concerned, there are too many concerns about small 2S animal experiments, experiments with small numbers of BFG08128 118 Dr. Epstein - Cross 1 animals ? 2 A. You couldn't be more right. 3 Ql And, by today's standards, they say we do not look 4 at those as meaningful. 5 A. NO. 8 Q. If I showed up with a four-animal study down in one 7 of the governmental agencies, they would throw me out B of there,wouldn't they? 9 A. Ah hah, let me say what they would do to you. 10 Ql Well -- 11 A. First of all -- hang on a second, let me tell you 12 what they would do. 13 If the data were negative, you are 14 absolutely right, they would kick you out on your ass. 15 However, if you came in with studies, 16 with birth defects in four mice or four rats, affecting 17 all the progeny, and these animals had three heads on 18 them and none of the controls had three heads, they 19 would say -- in other words, an unusual birth defect, 20 they would say, look, friend, these data statistically 21 are not valid. You've got something pretty rotten here- 22 You've got something pretty rotten here. You've got a 23 birth defect here. You've got a very unusual birth 24 defect in a small number of animals, none in the controls 25 This, to say the least, is extraordinarily suspicious. BFG08129 119 Dr. Epstein - Cross 1 Now, make sharp distinctions.between 2 that and between claims on the negativity, on the absence 3 of effect based on small numbers. 4 So, the way you would be received, 5 sir, would depend on what gifts you brought; whether you S brought the positive results of unusual effects, or 7 the absence of effects and you said, look, there is a nothing here, why don't I register this material and 9 expose millions of people to it. 10 Q. If I came in with four animals with one defect, 11 the overwhelming probability is that no scientist in 12 the area would pay any attention to it whatsoever, right 1 13 A. Well, when you say four animals, do you mean four 14 pregnant rats, or four pregnant mice, each with one IS defect in all the litters of all of them? 16 0 No. I just mean there is -- there were four animals 17 and I administered a substance. 18 A. Four pregnant animals, okay. 19 Ci Four pregnant animals. 20 A. Fine. 21 CL And I administered a substance. 22 A. And four controls. And how many controls then? 23 Q, Four controls. 24 A. Okay. Four pregnant animals in the test group, and 25 four pregnant animals in the controls. BFG08130 120 Or. Epstein - Cross t Ql And I got an abnormality. 2 A. In just one animal, in just one litter, one baby 3 in one litter, one would say well, look, you now, this 4 is nothing to write home about, go and get lost, chum. 8 One would not be interested in that. 6 If, however, in two or three litters of 7 these four animals you had unusual birth defects and 8 none in the controls, and in fact when you looked up 9 your agency files you found that there were half a dozen 10 other of these experiments, all of which with varying 11 degrees of animals showed positive effects, one would 12 say, now, look, this is very interesting. Why don't 13 we mount more studies on this strain of animals which has; 14 not been done, incidentally, on the two positive strains 18 of rats, why don't we mount large-scale studies on the 16 mammalian species like pigs and dogs? That's the respond; 17 for one to have. And, in fact, the results with the 18 pigs and dogs you see down there are positive and 19 equivocal, you have two positive results in rats, in 20 two strains of rats, the Wistar rat, the Sherman rat, 21 and the Ciba-Geigy you used a different strain. 22 Q. Are you mad at me? 23 A No, not in the slightest. I am trying to explain. 24 I think we are developing a reasonable pattern of 28 communication at last. BFG08131 121 Dr. Epstein - Cross 1 ql Can't you turn off a little after I just ask you 2 a simple question, can't you just give me a simple 3 answer? 4 A. Well, I am trying to be as helpful as X can to you, 5 but it appears that a certain amount of repetition is 6 necessary. Otherwise you ask the same question twice. 7 Cl Well, I am simply trying to find out whether one 8 unusual result in a litter of four animals would be takeii 9 seriously? I think you told me no, it wouldn't. Then 10 you went on to a long explanation as to why -- 11 A. No. You changed your question. Initially you 12 were talking about one litter -- one animal amongst 13 four, and then I tried to find out from you whether you 14 were talking about one baby in four litters which may 16 be one in fifty. There is'a difference. 16 Q. At least then the process of evaluating these 17 different studies to say whether they give you evidence 16 that is meaningful should be done by people who know 19 their business, and X assum you are holding out to. me 20 that you know your business. You say, by gosh, I am 21 good at this. 22 A. Well, those weren't my exact words, but X am willinc 23 to accept your paraphrase. 24 Q. All right. Now let's go here. You have some 25 studies up here and you have a plus mark on some egg BFG08132 122 Dr. Epstein - Cross 1 studies. Do they recognize egg studies as being good 2 studies? Do they tell you something about -- 3 A. Well, to be quite frank, 1 have done a vast amount 4 of egg work myself. 5 Ql For godsakes, doctor, don't tell me what your 6 opinion is. Do they? 7 A. i was just going to comment to say, in general, I 8 think the position amongst most people is that it 9 would be pretty rash to develop clear inferences on 10 the basis of egg data. And, Z share that too. 1 would 11 be very unhappy about accepting clear inferences of 12 positivity on the basis of egg data. 13 All I think .that the egg data can do is 14 to show you whether or not the material is suspicious 15 and the degree of suspicion. So, Z would say the answer 16 is, you shouldn't rely on egg data in a definitive 17 fashion, but it is reasonable to take the position that 18 it provides you suggestive data. That's the kind of 19 thing. Zt is a screen test. 20 Q. is it reasonable to say that a subject is -- to be 21 teratogenic, a substance has to cross the placenta 22 barrier and affect the fetus? 23 A. Yes, I think so. And, this is the reason why 24 one has certain reservations about drawing hard and 25 fast inferences from egg data. I fully accept this. BFG08133 23 Dr. Epstein - Cross 1 And the placenta barrier is the covering around 2 he mammalian fetus? 3 You are absolutely right. There are differences, 4 lear differences between the egg, the physiology of the 5 gg in chicks or ducks, and the physiology of a human 6 gg, the human embryo. And, for this reason, I think 7 ne has to be cautious, although in fact the FDA studies 8 ave shown a fairly interesting concordance, or 9 imilarity between some of the chick egg studies and 10 one of the rodent studies. 11 Now, Doctor, pick out for me, if there is one, the 12 me study on which you put a plus that you think is the 13 tost important study supporting your opinion. 14 Well, you know, I said very clearly in the deposi IS tion that I am relying on the aggregate of the data. 16 : am not prepared -- I was not prepared then, and I am 17 sot prepared to say now that this study is the most 18 .mportant. 19 What I am saying is, we have several 20 positive studies; each of them which have different 21 strengths and different weaknesses, and the aggregate jf all of these I find persuasive. As indeed many other mthors in the literature also find persuasive. )i Like whom? L Well, I may be in contempt of court if I go into BFG08134 L24 Dr. Spstein - Cross 1 ;his again, but we already had a chart this morning 2 from which you insisted that I excluded several authors 3 *ho made statements on teratogenicity of Diazinon. If 4 fou would like me to go over these and with the consent 5 sf the Court, I will do so. 61 7 Well, we have taken a lot of time already. This Kimbrough and Gaines study in 1968, 8 iid that have an adequate number of animals by today's 9 standard? 10 I Well, that is a good question. I said before that 11 today's standards, in general, tend to like about ten or 12 so animals per dose level. I would say that on a whole 13 the Kimbrough and Gaines Study was a bit short on animal 14 It had four to six animals in a group, in a test group, IS and it had four to six animals in controls. But, there 16 were three control groups in the Kimbrough and Gaines 17 Study. 18 Furthermore, the losses, the birth 19 defects which you got in the Kimbrough and Gaines Study 20 were extraordinarily similar to the birth defects in 21 found in the Dobbins Study. That is the study immediately 22 above. Those two. Very similar birth defects. The Dobbins Study was with Wistar strain of rats; the Kimbrough and Gaines Study was with the Sherman strain of rats, and both of them found renal BFG08135 125 Dr. Epstein - Cross 1 defects of the -- defects of the renal tract. Very 2 interesting. 3 So, when you say to me, do I exclusively 4 rely on the Kimbrough and Gaines Study, the answer is 5 no. It is a study I would like to see more animals in 6 it. However, there were three groups of controls, there 7 were birth defects similar to the defects found in other a studies, and these, I think, are very very interesting 9 indeed. 10 Ql Well, Doctor, I am basically going to give up on 11 you because I just can't keep going and all I asked 12 you -- the only question I asked was, in the Kimbrough 13 and Gaines study was there an adequate number of rats 14 by today's standards. It seems to me you can answer that 15 yes or no, and it took -- it took 15 minutes. 16 At any rate, in judging whether these 17 studies are indicative of teratogenicity in man, people 18 could have a difference of opinion with yours, couldn't 19 they? 20 A. I would say that if you show data of this kind where 21 you have several positive studies in animals, when some 22 of these studies show similar birth defects in different 23 species, on different strains, the most some people -24 you might have a difference of opinion this way: Some 25 people would say there is a high degree of probability BFG08136 126 Dr. Epstein - Cross 1 this is teratogenic in humans ;* others would simply say 2 there is a possibility, or there is a suspicion. I am 3 willing to accept the fact that there may well be a 4 difference of opinion between some scientists who say 5 there is a suspicion that this produces birth defects a in humans, or those who go stronger and say there is a 7 high degree of probability. In that respect I totally 8 agree with you, between good men of -- and women, excuse 9 me, but in good people of faith and training in the 10 area, there could well be a difference of opinion between 11 those who look at data of this kind and talk about 12 suspicion of teratogenicity on the one hand or proba 13 bility, that I fully accept. 14 & Do you know Dr. James G. Wilson, don't you, or of 15 him? 16 A. Yes, I do. 17 Q. Do you accept him as a competent authority in the 18 field of teratogens? 19 A. Certainly he is a most competent bench teratalogist 20 but I wouldn't accept him as authoritative in the area 21 of human risk evaluation. 22 Q. Well,' you would accept him as an authority in the 23 field of deciding whether various tests indicate 24 teratogenicity in the animals? 25 A. As X say, i think the man. Dr. Wilson, is certainly BFG08137 127 Dr. Epstein - Cross 1 a most competent teratologist There is no question 2 at all. 3 Of his professional ability in the 4 area of risk assessment -- and we have had differences S of opinion on this which I would be happy to discuss 9 with you if you care to, I would, with due respect, 7 raise some guarded qualifications, and, these qualifi a cations, incidentally, have been shared by governmental 9 agencies,and the Administrative Environmental Protection 10 Agency rejected recommendations of his committee of a 11 committee which he chaired on ability of 245T to 12 produce birth defects. Dr. Wilson looked at a great 13 deal of data in 1972 on 245T, a herbicide for which 14 there was overwhelming evidence on causes of birth defec 15 -- this is the Agent Orange chemical -- and he came to 16 the conclusion that there really wasn't much hazard 17 in this and I took a different position and the 18 adminstrator. of the Environmental Protection Agency, in 19 an action unprecedented in the regulated history of the 20 United States rejected the opinions of his advisory 21 committee, including the opinions of Dr. Wilson. 22 So, as I said before, I think in terms 23 of experimental teratology, fine; in terms of human 24 risk evaluation, with due respect and -- really, with 25 due respect I would question his ability to make BFG08138 28 Dr. Epstein - Cross 1 nf erences on risk assessment. 2 If your are criticizing. Doctor -- I take it 3 ha t was a criticism of Dr. Wilson? 4 No, no. I said that I think that he is highly 5 6 It is just an attempt -- 7 Excuse me. 8 -- that he wasn't good. 9 No, no, not at all. I said I think he is highly 10 ;ualified as a professional teratologist. In the area 11 f professional risk assessment, of assessment of risk 12 :o humans, I have indicated that there is a history on 13 rhich he has taken positions contrary to the positions 14 >f many many professionals in this country, and position 15 -- his positions having been rejected in an unprecedented 16 lashion by the Environmental Protection Agency in 1972 - 17 71. 18 L What was the reason for doing that? 19 Well -- 20 t Again* 21 u The reason basically -- 22 l Do you accept him as an authority in his field or 23 ion't you? 24 l Well, you know you asked me before why I give you O 25 Lengthy answers. You are coming back and asking me the M BFG08139 129 Dr. Epstein - Cross 1 same question repeatedly, and 1 am willing to repeat my 2 answers, but I am afraid by doing this we are trying 3 the patience of the Court. 1 have already answered 4 very substantively, and if you wish me to repeat this, S I will. 6 Q. I don't want you to repeat it. God only knows, 7 I'm not sure where we are, to tell you the truth with 8 that answer. You simply -- I gather you are saying, 9 yes, you accept Dr. Wilson as am eminent authority, 10 but there was an instance in which he and some other 11 people in the government disagreed. 12 A. Sir, you do misquote me, and, really, this is most 13 unfortunate. 14 What I said was that Dr. Wilson is 16 a most experienced and an excellent bench teratologist. 16 He has done very fine fundamental studies on teratology 17 in animals. 18 When it comes to human risk assessment, 19 the question of assessment of risk to humans, he has 20 been characterized by many as highly conservative. And, 21 the instance I have given you of a committee which he 22 chaired and which is recommendations on public policy 23 were ignored and rejected by the federal agency to whom 24 he was reporting, this is an example of questions that 25 may be reasonably direct on his qualifications in the N <4 BFG08140 130 Or. Epstein - Cross 1 area of risk assessment. 2 Nov, i hope that is clear, sir. 3 Qi As far as you are concerned, what does "Nature 4 Magazine," think of you? 5 A. Well, "Nature Magazine" is a journal that publishes 6 opinions from qualified scientific people. A journal 7 never thinks of, be it all badly, of anyone. A journal 8 is prepared to publish opposing viewpoints and opposing 9 viewpoints of positions X have taken have been published 10 in "Nature" and elsewhere. 11 Q> So, we don't want to get into incidents where 12 somebody has not gone along with somebody else. 13 A I am not really talking about incidents. I am 14 talking about the fact that when recommendations on 15 public policy effecting the lives of millions of women 16 in this country are concerned, he made a recommendation 17 that it was no hazard from 245T. The scientific data 18 were contradictory to that, and X was involved in 19 marshaling of the scientific data which took a contrary 20 position and presenting this in Washington and the 21 Admistrative Environmental Protection Agency decided i 22 with due scientific advice to reject the recommendations 23 of Dr. Wilson that indeed 245T was safe. And, the 24 subsequent experimental data in the last ten years has 25 confirmed the fact. We have dozens of experiments now, BFG08141 131 Dr. Epstein Cross 1 -designed experiments with large' numbers of animals 2 demonstrating that 245T is teratogenic. 3 TEE COURT: Excuse me, Dr. Epstein. 4 I think to summarize, and I think we better drop it 5 at that, you have said you do accept Dr. Wilson as a 6 competent bench teratologist, but you would not accept 7 him as authoritative on human risk evaluation. 8 THE WITNESS: Thank you, sir. 9 THE COURT: I think, Mr. Griffin, perhaps 10 we move along. 11 MR. GRIFFIN: Well, sir, I am virtually 12 finished. 13 THE COURT: I know, but we are now trying 14 245, whatever that is, and I am not interested in 15 injecting new matters before the jury. 16 MR. GRIFFIN: I just wanted to recap 17 where we were in this case. 18 THE WITNESS: Sure. 19 BY MR. GRIFFIN: 20 Ql In this case, because we don't have human risk 21 factor data, we are limited, really, in trying to 22 decide whether there, is a teratological effect in humans 23 to a study of the effect in animals. And, we have to 24 make sure that the animal studies do show what you 25 say they show. BFG08142 132 Dr. Epstein - Cross 1 A. Excuse me, two points. First o all, we have the 2 absence of human risk data. We have the fact that she 3 was not exposed to any known teratogen, that is point 4 one 5 Point two, when you talk about the 6 statements which I make in teratogenicity, this is 7 misleading. A whole series of statements on the * 8 teratogenicity of Diazinon have been made by a wide-range 9 of experts in this field, some of which are allowable, 10 some of which I have been barred from presenting to the % 11 jury. So, I am not expressing just a personal opinion. 12 There have been a wide-range of statements by authorita t 13 tive scientists in government and elsewhere that Diazinoi. 14 is teratogenic. That, plus the absence of any risk flM U U IM II. -*. |tf* VIM *^ 15 fact, known risk factor in pregnancy. She didn't get % 16 rubella, she didn't get German measles, she didn't get 17 x-rayed, she didn't have a previous child with birth 18 defects. So, you have mischaracterized my position in 19 summing it up in the way you have. 20 Ql Doctor, I thought in this case all of your judgment 21 on whether it is teratogenic or not come from animal 22 studies. ? 23 A Two points: One, it comes from the animal data, < 24 which is one point. But, over and above my evaluation 25 of the animal data, a wide-range of other experts have i BFG08143 33 Or. Epstein - Cross 1 ome to a similar conclusion, that Diazinon is indeed 2 eratogenic. And, therefore what I was pointing out to 3 ou, that my evaluation of the teratogenicity data is 4 ot unique, as you were attempting to suggest. 5 You talk of wide-range of experts, you are simply e liking about people that show up in these studies. 7 No I am not. X am talking about many others, and 8 ou have barred me from making reference to the state9 ents of these other experts. If the Court permits me, 10 will do that. 11 Do you wish me to do so? 12 X am not -- I don't know whether I do or not, 13 octor. I don't know what you have or what you don't 14 IS Do you wish me to -- ie You have not given me an -- 17 THE COURT: Mr. Griffin, why don't you 18 top arguing with the witness. 19 MR. GRIFFIN: All right, sir. X suppose 20 shouldn't. X suppose X shouldn't. X will let it go 21 t that. 22 THE COURT: Do you have any questions, 23 x. Candless? 24 25 MR. McCANDLESS: Yes, sir. THE COURT: You may proceed. BFG08144 134 Or. Epstein - Cross 1 CROSS-EXAMINATION 2 BY MR. McCANDLESS: 3 ft Doctor, is Diazinon teratogenic in horses? 4A I don't have the slightest idea, 5 ft Why not? 6A I don't believe Ciba has tested it, or if it has 7 tested it it has not released the data and I don't know 8 if any other scientist has tested Diazinon in horses. 9 It is not a common experimental animal in teratogenicity 10 to the best of my information. 11 ft What about -- I've got a list here. What about 12 goats? Is it teratogenic in goats? 13 A To the best of my knowledge, Ciba has not tested 14 this. 15 ft Well -- 16 A To the best of my knowledge there are not publishet 17 data on the teratogenicity of Diazinon in goats, which 18 again doesn't happen to be a common or usual experimental 19 animal. 20 Now, we can go through a whole 200 21 if you'd like and you will get a similar answer, except 22 for animals which we discussed; namely, the mouse, 23 the rat, the hampster, the rabbit, the pig and the dog, 24 and perhaps more recently some experiments on primates. 25 I don't know if that saves any time. ' BFG08145 135 Or. Epstein - Cross 1 Cl Well Doctor, is Diazinon teratogenic in elephants? 2 A. X don't have the slightest idea. 3 Qi 4 A. Why not? For the same answer I have given you before for 5 goats and horses. 6 ft Because what, you haven't read anything that says 7 it is? 8 A. No. No. No. Because X am unaware it has been 9 tested. 10 Oi Okay. 11 A. If there were data on the test results, I would be 12 happy to evaluate them and give you an opinion. Perhaps 13 you have.such data which you would like me to look at. 14 & Well, let me go on, one more. Is Diazinon terato 15 genic in kangaroos? Xf you know. 16 A. I am afraid X have to answer the same way as the 17 previous answers. 18 Qi You know of no tests having been done on kangaroos? 19 A. No, I am not aware of it. But, it is possible X 20 missed it. 21 Qi Is Diazinon teratogenic in man? 22 A. X would say that there is a strong presumption that 23 it is teratogenic in humans on the basis of positive 24 data in rats, in two strains of rats, and in rabbits and 25 in pig and dog. BFG08146 136 Or. Epstein - Cross 1 Q. Well, Doctor, for a kangaroo you said no because 2 there was no study in a kangaroo. 3 A. I didn't say there was no study.* I said I was 4 unaware. That is very different. S Q. Well, what is the study in man that you are aware 6 of that says Diazinon is teratogenic in man? 7A I didn't say teratogenic -- it was -- now look, a I think we are going to waste a great deal of time if 9 you misquote me. Please do not do this. I stated 10 clearly and explicitly that there .was a strong presumptio 11 or probability. Now, you have taken that and quoted me 12 as saying that it is teratogenic in man. I object 13 strongly to these legal tricks. 14 Q> All right. So then you disagree with my statement 15 and you would say that Diazinon is not teratogenic in 16 man. You disagreed with how 1 characterised it.. 17 A I have characterized it in the way which I consider 18 proper; namely, that on the basis of experimental data, 19 there was a strong presumption or probability that 20 Diazinon is pregnant in humans is teratogenic in 21 humans. 22 a Do you know the names of any other human, other than '23 someone conceivably involved in this case, that had a 24 birth defect because of Diazinon? 25 A No. No. But, it is -- as I said before, you have BFG08147 137 Dr. Epstein - Cross 1 an overwhelming majority of cases with birth defects 2 that are never investigated. 3 ft All right. Are you an investigator of birth 4 defects? SA 1 think I have discussed my professional expertise 6 in some detail this morning. X do not make a profession 7 out of investigating birth defects. I have advised 8 governmental agencies, X have advised and still advise 9 the March of Dimes how to go about studying this, but 10 I do not spend my time exclusively in these areas. 11 Qi Okay. Are there people who do? 12 A Certainly. Certainly. There are some epidemiolo 13 gists, particularly in the Center for Disease Control, 14 who do their best with the very limited data they have. 15 But, as X said before, the basic information which you 16 need, namely a birth defects registry, or parental, 17 maternal and paternal occupation on birth certificates, 18 we don't have these data, but, nevertheless there are 19 epidemiologists in CDC and elsewhere who study these 20 matters, and there are experimentalists who study these 21 matters, and there are people in the area of risk 22 assessment too. There is a wide-range of areas for the 23 data base. As far as humans are concerned, to say the 24 least it is grossly inadequate. 25 Q. Are you and epidemiologist? BFG08148 138 1 A. No. Dr. Epstein - Cross 2 Q. Would you rely on another epidemiologist if you a wanted to know something about epidemiology? 4 In general, when I have problems in epidemiology S I discuss these with colleagues in the field and take 0 opinion and advice from those who are recognized as 7 being professionally competent in the area, certainly. 8 0- Doctor, do you know when Diazinon was created? 9 A. Created? 10 by that? That is a strange word. What do you mean 11 0 Well, did it come to us with the formation of the 12 earth? It is not a natural compound, is it, or is it? 13 A. Do you mean when was it synthesized? 14 0 Whatever you want to make it. 15 A. Okay. Well, that is different. I believe a 16 patent was taken out in about *51, to the best of my 17 memory, and Ciba-Geigy started marking it in about 1954. 18 That is to the best of my recollection. I may be off 19 by a few years, that I think that is basically the -- 20 1 may have some -- I think that was -- yes. I think it 21 was marketed in '54. Sure. 22 gi How long has man been on this earth? 23 A. Well, you know, it depends on whether you are a 24 creationist or not, and I am not sure this Court would 25 permit a discussion of evolution in this area. I just BFG08149 139 Dr. Epstein Cross 1 don't know. 2 Cl Will y.ou accept a million years? 3 A. I am willing to accept any hypothetical you are 4 willing to offer. 6 ft When did cleft palate first appear on this earth? 6 A. Well, you know, in the ancient papyri, I believe 7 there are records in times of Egyptians of birth defects . B including cleft palates. 9 Q, Did the Egyptians have Diazinon? 10 A. To the best of my knowledge, no. I think I told 11 you that Diazinon was synthesized about 1951, and I am 12 not sure at what point the repetition of the question 13 is. If it was synthesized in 1951, how could the 14 Egyptians have been using Diazinon; the early Egyptians, 16 the ancient Egyptians, I mean. 16 On the other hand, there have been many 17 instances of acute toxicity in organic phosphate 18 pesticides in Egyptians, Egyptians in the course of the 19 last decade or so, including massive numbers of buffalo 20 kills from organic phosphate pesticides which were 21 manufactured in this country and exported without any 22 labels or warning on these problems to Egypt. I am 23 willing to discuss this, if you so wish. That was 24 an Egyptian episode. 25 Cl Well, let me just get this straight, leaving the BFG08150 0 Dr. Epstein Cross 1 Egyptians in or out of this. Cleft palate and cleft 2 Lip certainly came long before Diazinon. 3 L Oh, you are absolutely right. 4I Thank you. 5 Well before Diazinon, what would we 6 ?lame cleft palates on? 7L I had gone through a list of risk factors in respond e : your colleague's question. Would you like me to 9 repeat the same list of risk factors for humans? I thin); 10 ihe record is very very clear as to what I said causes 11 risk factors, but I am willing, if the Court wishes, to 12 repeat the same list again. 13 1 You needn't do that. We heard it once, 14 L Well, you asked the question a second time, IS i It is pretty clear to say that certainly you couldn 16 clame any of those clefts before 1951 on Diazinon. 17 I In the absence of an exposure to a teratogen, IS you cannot blame the teratogen or incriminate the 19 teratogen for the birth defect. That is fairly obvious, 20 Q. And, Doctor, is that a yes answer or a no? 21 FL I have answered, I think, fairly simply. 22 & Can you blame pre-1951 birth defects, cleft palate, 23 cleft lip, on Diazinon? 34 A I have already said no. 25 Q. Thank you. BFG081.51 141 Dr. Epstein - Cross 1 A, For the reasons I have given. 2 Ql Where are Diazinon's fingerprints on the McConnell 3 cleft? 4 A. There aren't any. In fact, the majority of 5 adverse effects in the environment, whether cancer or 6 birth defects, or genetic abnormalities, there are no 7 pathognomic, or fingerprints to say this cancer is due 8 to that chemical, or this birth defect is due to that 9 particular chemical. It is very very rare that you can 10 have -- you can state by looking at a particular cancer, 11 or this or that, or birth defect, this is due to exposure 12 to that agent. 13 ft You can't do that in this case either, can you? 14 A. I just told you. 15 Q, You said that in part you relied upon what you 16 perceived to be an absence of exposure in Diane McConnel 17 to known teratogens, is that correct? 18 A. Yes. 19 Q Well, I think in your earlier testimony, and I know 20 you will correct me if I am wrong here, but, you led me 21 to believe that certainly almost no compound can be 22 excluded simply because there is no data on it, is that 23 correct? 24 A. Yes, certainly. There is a great deal of different 25 between actual data showing that a material is BFG08152 142 Dr. Epstein - Cross 1 teratogenic than the absence of data which would not 2 allow you to pass an opinion one way or another. But 3 here we have clearcut exposure to an agent which has 4 been demonstrated to be teratogenic in several animal 5 species and several strains. We don't have data on 6 teratogenicity of any other materials to which she was 7 exposed. 8 Now, I am not willing to exclude the 9 possibility that there were other materials in the 10 environment. I don't know. I am not prescient. All 11 I can do is to offer the Court an opinion based on the 12 evidence that is available. 13 Now, if you hypothesize on something 14 on which X have no data, I am not in a position to 18 be helpful to you. 16 & Did you give Diane McConnell a checklist of 17 possible teratogens so you can know this? 18 A X gave her nothing. I have never met Mrs. 19 McConnell until this morning, but X asked Mr. Bolden 20 if he would please inquire into a range of exposures 21 and factors. 22 Ql Mr. Bolden did this for you? 23 A I asked Mr. Bolden if he would get this information 24 for me, and make this information available to me. 25 Q. What checklist did you give him to find out what BFG08153 143 Dr. Epstein - Cross 1 the exposure to other -- 2 A. I have already told you that -- 3 Q. You gave him that checklist? 4 A. Would you allow me to finish before firing 5 staccato questions? 6 I told Mr. Bolden that I needed informa 7 tion covering a wide-range of factors, including any 8 drugs she took in pregnancy, tobacco, alcohol; I went 9 into a very wide-range of possible environmental 10 influences with Mr. Bolden and I got information on 11 all of those. 12 I got information on drugs, lack of 13 radiation -- 14 Q. Doctor -- 15 A. -- alcohol, tobacco, and allother exposures. So, 16 the answer to your question is, while I do not have a 17 formal checklist in front of me of factors one to twelve, 18 I inquired about all factors which I considered. 19 Ql Okay. Well, Doctor, if something werecarcinogenic, 20 would you -- that means it causes cancer. Maybe we are 21 bandying about words here that not everyone is totally ; 22 familiar with. Doesn't it, carcinogenic means capable 23 of causing cancer? 24 A. That's right. 25 Qi If you suspected a compound as being carcinogenic. BFG08154 144 c Dr. Epstein - Cross 1 would you also have suspicions about its teratogenicity7 2 A. Well, that is a good question. One of the 3 difficulties of answering this is that we don't have 4 good comparative data on a large number of carcinogens 5 and a large number of teratogens. There have been 6 suggestions based on smaller numbers that there is an 7 association between the two. I don't think the 8 association is an obligate one. I don't think it is a 9 very clearcut association. But, there are some sugges 10 tions of an association. 11 It is clear that some carcinogens do 12 induce teratogenic effects. But, that doesn't mean to 13 say that there is a close association between them. .14 Q. There is a lack of -- 15 THE COURT: Just a moment, Mr. McCandless 16 May I see counsel at side bar, please? 17 (Side bar discussion on the record, 18 as follows:) 19 THE COURT: I don't want to limit ,anybody 20 By the same token, I don't want to cause unnecessary 21 expense. But, I do not want to press the jury too hard. We have pushed them pretty hard. I take it you are going to be awhile? MR. McCANDLESS: I may well be. THE COURT: Particularly if you are goinc BFG08155 145 Or. Epstein - Cross 1 to go over the same ground Mr. Griffin has already 2 covered. 3 MR. McCANDEESS: I don't think 1 have 4 done too much of that already, have I? 5 THE COURT: It all depends if 80 percent e of what you have done is too much or not too much. 7 In any event, I certainly am not going 8 to cut anybody off. But, t am not going to push the 9 jury any further. it is now 4:15. They have been 10 sitting without a break for two hours. I am going to 11 excuse them until 9:30. 12 Unless -- if I knew -- Mr. Griffin. 13 If I knew that five or ten minutes 14 more would save a witness fee, I will -- but I -- 19 MR. PERRONI: Your Honor, the witness id does have a plane that he would like to catch at 17 7 o'clock tonight. With all due respect to the Court, 18 if we could finish today, we would appreciate it. 19 THE COURT: Yes. But, you would have 20 to say, with all due respect to defense counsel, and 21 defense counsel are not about to accommodate this 22 witness, I don't think. 23 Am I correct in my assessment? 24 MR. McCANDLESS: Yes, your Honor. 28 I think you are right. BFG08156 146 Dr. Epstein - Cross 1 MR. SPALDING: Perhaps we could inquire 2 of the jury if they would be willing to indulge us to 3 hear the end of this witness' testimony. 4 THE COURT: I think as good citizens S they would say -- they would stay here until 9 o'clock e if I asked them to. I simply am not going to ask them 7 to. 8 MR. SPALDING: All right. 9 (End of side bar discussion.) 10 THE COURT: Members of the jury, having 11 due regard for the principle that the hardness of a seat 12 after one has been sitting too long affects the ability 13 to absorb, I think we will call an end to today's 14 session, although I gather it will cause some inconven 16 ience to the witness. 16 So, we will recess now until 9:30 17 tomorrow morning. 18 (The jury withdrew from the courtroom 19 at 4:15 p.m.) 20 (There was an in-chambers conference 21 at 4:17 p.m., concluding, at 4:30 p.m., at which time 22 court adjourned.) 23 24 25 bFG08157 147 1 (Proceedings for December 10, 1982.) 2 (Court convened at 9:55 a.m.) 3 THE COURT: Good morning. 4 The witness may return to the stand. 6 6 7 stand.) (Dr. Samuel Epstein resumed the witness 8 CROSS-EXAMINATION(Continued) 9 BY MR. McCANDLESS: 10 ft Good morning, Doctor. 11 A Good morning. 12 ft 13 A 14 ft Did you meet with plaintiffs' counsel last night? Well, we had dinner yesterday together, yes. Did you discuss this case? 15 A 16 ft 17 A No. No Not at all? No. We talked about music and many other matters, 18 but not the case. 19 MR. McCANDLESS: Your Honor, I would lik 20 to make a motion about this witness. I feel that during 21 22 23 24 follows:) THE COURT: Come to side bar. (Side bar discussion on the record as 25 MR. McCANDLESS: Your Honor, I think tha BFG08158 148 Dr. Epstein - Cross/Side Bar 1 under these circumstances, the witness having met with 2 counsel while he i's under oath and in the process of 3 being cross-examined, its impropriety, at least some 4 sort of instruction should be given for that, or at S least move to strike his testimony. 6 THE COURT: Motion denied. 7 (End of side bar discussion.) 8 BY MR. McCANDLESS: 0 Cl Okay, Doctor, last night when we left off, I think 10 we were asking about what you did to determine what othe 11 possible teratogens Mrs. McConnell might have been 12 exposed to. 13 When were you asked to consult in this 14 case ? IB A I think it was about in June or July of 1980. 16 Q. At that time suit had already been brought, hadn't 17 it? 18 A I beg your pardon. 10 Q, Had suit already been brought at that time? 20 A I have no idea. 21 Q. who did this literature search for you? , 22 A This- was done Toxline and Medline, and commissioned 23 by Mr* Bolden. 24 These are automated computerized 25 literature searchers that you pay a fee. You feed in BFG08159 X49 Dr. Epstein - Cross 1 the key words, like diazinon,^or whatever you are 2 interested in, and they produce the information for 3 you. 4 Ql Mr. Bolden supplied you with this literature. 5 A. Yes. 6 ft In your deposition which we took in Chicago in 7 August of 1981, you said that you had only been asked 8 to consult in this case some five months before the 9 deposition. 10 A. That was a mistake. It was in fact the summer 11 of 1980. 12 Ql We did come to Chicago to depose you; you recall 13 that? 14 A. Yes, 1 do. 15 Q. And, you charged us a thousand dollars for your 16 time on that single day, isn't that right? 17 A Yes, that's correct. 18 Q. And, that time, as now, you presented yourself as 19 being an expert in reading literature, is that correct? 20 A That was not the language I used. I presented 21 myself as an expert in toxicology. 22 0. And at that time you read the 1974 Baselt Rat 23 Study backwards, did you? 24 A Yes. In fact, I got the Baselt report fairly 25 shortly before the deposition, and 1 really hadn't had BFG08160 150 Dr. Epstein - Cross 1 an adequate amount of time to look into it as thoroughly 2 as I did subsequently. 1 think I pointed out right 3 at the beginning of the deposition that I had by no 4 means completed my literature review. 5 ft But, at that time, your conclusion was that that 6 showed some sort of teratogenic effect. 7 A. That's correct, 8 ft And it in fact didn't. 9A Well, I wouldn't say it is totally without any 10 effect at all. But, there is no question that I 11 misread one table. However, there are certainly some 12 other interesting aspects to the Ciba-Geigy 1974 report, 13 which make it not entirely without blemish, 14 ft But now you changed on your chart from a plus to 15 a minus? 16 A That's right, yes. 17 ft Doctor, in the request that was presented to you 18 about this case, were you asked to find the cause i 19 for the birth defect, or were you asked whether Diazinon 20 was involved? 21 A I was just asked to review the files and to see if 22 I could come up with an opinion as to the causes of the 23 birth defect. 24 ft And, Diazinon had been suggested to you, hadn't it? 25 A I was presented with a background document and BFG08161 151 Or. Epstein - Cross 1 asked to review them and asked to see if I could come 2 up with an opinion. 3 0- 4 A. Diazinon was suggested to you at that time. Well, to be quite frank with you, I don't remember 6 exactly the nature of the original letters and the 6 conversation, but 1 was told, among other things, that 7 she had been exposed to pesticides in her early 8 pregnancy, yes. 9 ft You have the original letter with you, don't you? 10 A X am afraid I don't, no. 11 ft You didn't bring that? 12 A. No. But, X am prepared to concede there was a 13 -- certainly in the correspondence, or in the discussion 14 there was reference to spraying of pesticides, including 18 Diaizinon. And, that in fact was the basis for the 16 literature search in Diazinon in fact. 17 ft Okay. Did you consider the possible effect of 18 Mrs. McConnell's having worked near a cathode ray tube? 19 A I considered it, but didn't feel on the basis of 20 the information I had that there was any evidence relati 21 such exposure to birth defects. 22 ft Did -you do a literature search on that? 23 A No, I didn't. 24 ft What about her use of alcohol or tobacco? What 25 did you do to find out about that? BFG08162 152. Dr. Epstein - Cross 1 A. Well, I specifically inquired about all these 2` matters, and you are quite right in pointing direction 3 in those areas. 4 First of all, as far as tobacco is 5 concerned, she did smoke certainly at one stage, but 6 she gave up smoking as soon as she discovered she was 7 pregnant. 1 believe that was the exact time. 8 Over and above that, she did take 9 alcohol very very briefly. I think over Christmas 10 when she was pregnant. She said that she had taken, 11 X believe, one to two glasses, or something of that 12 kind. So, in fact, she didn't take alcohol during 13 pregnancy, with the exception of about one to two 14 glasses of alcohol in Christmas of '78. And, as I IS said before, she stopped smoking as soon as she 18 discovered she was pregnant with Kristine. 17 Qi Isn't that somewhat contradicted by the medical 18 records you were given on this lady's delivery and her 19 health before that time wherein it was indicated that 20 she was smoking one-pack-and-a-half a day? 21 A. You are absolutely right. There is one record of 22 Dr. Dayman, in which it was said that she smoked one* 23 and-a-half packs a day. And X specifically inquired 24 about that and was assured by Mr. Bolden, who in fact 2S X asked him to go back and check with Mrs. McConnell, BFG08163 153 Dr. Epstein - Cross 1 that in fact that represented her past history, that 2 she had in the past smoked one-and-a-half packs of 3 cigarettes a day in her pregnancy, but that in fact she 4 confirmed to me, via Mr. Bolden, that she did not 5 smoke during this pregnancy. 6 In fact, in all the medical records I 7 saw, there was only one reference to her smoking in 8 pregnancy, and that was Doctor -- to the best of my 9 recollection, that was Dr. Hayman's note, which I am 10 assured is a mistake. 11 ft Doctor, have you brought all the records with you? 12 A. 13 ft 14 A. No, I don't have the medical records. Did you ever talk to Mrs. McConnell personally? Yes, I spoke to her yesterday and introduced myself IS and asked to see her daughter, and that is the first 16 time I have spoken to her or seen her. 17 ft Doctor, I realize you are not what you call a 18 bench teratologist, but you agree that in the field 19 of teratology there is a wide margin of error when you 20 ask a mother what it was she might have been exposed to 21 after delivery? 22 A. You are absolutely right. Buman memory is, mine 23 included, is frail at best. And, one can simply go on 24 good faith. 25 If indeed you question and question BFG08164 154 Dr. Epstein - Cross 1 repeatedly and repeatedly and you get an answer, "I 2 haven't smoked," or, "I didn't take alcohol," you know, 3 what else can one do but accept. 4 X am not denying the possibility that 5 an error was made, but all I can say is, X don't think 6 so. 7 How, if you ask me the basis for saying, 8 "X don't think so," I can't really tell you. It is 9 just my feeling that this is the truth. 10 0> Well, then, you are familiar, X take it, with the 11 literature of people who are bench teratologists, that 12 there is certainly a selective memory bias in women 13 who have had children with birth defects as to what 14 they have been exposed to during pregnancy. 15 A. With due respect, X don't think bench teratologists 16 would have any information at all on this. A bench 17 teratologist is someone who works experimentally with 18 animals and most of them have never seen a pregnant 19 woman, let alone -- in the course of their professional 20 activities -- let alone have any professional opinion 21 on this. i 22 The kind of person who X think would 23 be qualified in this area would be, say, the clinical 24 -- the clinical teratologist, or the pediatric teratolo25 gist on the one hand; alternatively, the psychiatrist. BFG08165 155 Or. Epstein - Cross 1 But, you are absolutely right, there 2 is selective memory. The most honest person can have 13 selective memory deletions, and I think the psychologica 4 literature abundantly attests to that, 5 ft And, doesn't the literature also say that in 6 cases such as this, a mother would be most inclined to 7 select something outside of herself, or outside of her 8 own responsible conduct to find to blame for the birth 9 defect? 10 A Hell, to be quite frank, I really don't want to 11 qualify myself in this area. X am perfectly prepared 12 on general grounds to accept the fact that we all have 13 selective memories. More than that X think you should 14 address your questions, with due respect to somebody 16 who is more qualified, like a behavioral psychologist, 16 or psychiatrist, or a clinical teratologist. 17 ft Doctor, in that Kimbrough and Gaines Study, when 18 I was that published, the one that you made reference to? IS A The Kimbrough and Gaines Study was published in 20 1968. 21 ft About 14, 15 yearsago? 22 A 23 ft Sure. And, another one of the ones you found positive 24 is Dobbins. 2S A Dobbins, yes. BFG08166 156 1 ft 1967. Or. Epstein - Cross 2 A. That's right. Yes. 3 ft And Green, you found -- what is that, positive, 4 1969? Is that right? SA Green, no. We have a plus-minus, which really 6 means equivocal. 7 ft Okay. What is the latest positive study that you e found? 9A The latest? I would say the Earle Study, 10 ft 1973. 11 A In 1973, yes. That's correct, 12 ft Nine years ago. 13 A 14 ft Yes. And, I think you have already explained that IS date you know of no federal regulatory agency that has 16 ever restricted the use of Diazinon with its relation 17 ship to pregnant women. 18 A That's correct. But, 1 also pointed out, I believe 19 I am unaware of any federal regulatory action with 20 relation to teratogenesis, with two possible exceptions. 21 With two exceptions: One, the FDA's position on drugs, 22 which originally required three-generation tests in rats 23 arid subsequently after the thalidomide episode, subse 24 quently required teratology studies; and also the 2S Occupational Safety and Health Administration Regulation BFG08167 157 Dr. Epstein - Cross 1 on lead, in which there was consideration of a variety 2 of effects, including teratological. 3 X should also just explain, NIOSH, 4 the National Institute of Occupational Safety and 5 Health, who has been credited with statements on e teratogenic actions and in whose Registry of Toxic 7 Effects of Chemical Substances, Diazinon is listed as 8 a teratogen, NIOSH has no regulatory authority. It 9 simply makes recommendations and does research and 10 reviews of literature, but has no regulatory authority 11 per se. 12 0- But, pesticides are regulated by EPA, isn't that 13 true? 14 A Yes, that's correct. 16 Qi And, you made reference on your chart to the 16 NIOSH document; is that true, NIOSH, what was it, 17 recommended standard for environmental exposure? You 18 made use of that? 19 A Well, I think the original standards on this were 20 developed by the American Conference of Governmental 21 Industrial Hygienists, or ACGIH. 22 Q. I didn't ask you about the source. I am asking 23 you whether or not you made reference to the document? 24 A No. Excuse me. You asked me about the standard, 25 and you asked me -- you implied it was a NIOSH standard. BFG08168 158 Dr. Epstein - Cross 1 Could we have that read bach? 2 ft . Let me withdraw the question, and I want to get 3 it clear. 4 Do you or do you not make reference in S your charts to the NXOSH document, Recommended Standards 6 for Occupational Exposures. 7 A. I see. Now, that's different. You said 8 recommended standard. 9 The document is called, "Recommended 10 Standard for Occupational Exposure," but, in fact the 11 actual recommendation for the standard came not from 12 NIOSH, came from the American Conference of Governmental 13 Industrial Hygienists. The document is entitled, 14 "Recommended Standards for Occupational Exposure." That IS is the basis of the ambiguity. ie ft 17 A 18 ft 19 Did you make reference to that document? Yes, sir. Thank you Have you had the opportunity to read 20 Dr. Farrow's deposition? 21 A Yes, certainly. 22 ft And, you know then that he was the author of the 23 pertinent sections -- well, I know he prepared the 24 draft of it. 2S A Okay. BFG08169 1S9. Dr. Epstein - Cross 1 A. Yes. But, this draft -- 2 ft You know he based it specifically and only on 3 Kimbrough and Gaines. 4 A. That is correct. 5 0 What was the birth defect, or teratogenic effect 6 in Kimbrough and Gaines? 7 A. Well, there were a series of different birth defect 8 ft With respect to Diazinon. 9 A. Excuse me. I am just -- 10 ft 1 just want to limit thequestion but -- 11 A. I am coming to the answer onthe Diazinon, and if 12 you please don't interrupt me I will give you your 13 answer. 14 ft Thank you. 15 A. There were a series of birth defects induced in 16 rats from the Diazinon, and they included renal 17 abnormalities, congenital renal abnormalities, which 18 incidentally were very similar to those observed in a 19 previous Study by Dobbins in Wistar rats. So, they 20 had renal abnormalities in 100 percent of -- I beg your 21 pardon, at one particular dose level of 100 milligrams 22 per kg, effecting about six-out-of-fifty animals. And 23 then at another dose level, at the 200 milligrams per 24 kilogram dose level, there are a series of birth defects 25 including hydrocephalus, which means a big head, that is BFG08170 160 Dr. Epstein - Cross 1 due to blockage of drainage of the spinal fluid, and 2 the head gets enlarged, progressively enlarged. 3 There is one hydrocephalus, one missing 4 phalanx, and another defect. In fact, there were about, S in the 200 dose level, there were three-out-of-six 8 defects. 7 Those were the basic defects which were 8 reported, and, you know, the study is certainly by no 9 means conclusive. It is -- there are defects in the 10 study and there are suggestive pointers in the study. 11 Q. Let me ask you about the high-dose range, they were 12 giving 200 milligrams per kilogram. 13 A. Yes, that's correct. 14 Ql Okay. Now, as a toxicologist, youwould agree, IS wouldn't you, that virtually every substance is toxic, 16 depending upon the right dose. 17 A. Absolutely. 18 Qi So, the fact that a substance may be toxic doesn't 19 mean it is particularly dangerous. 20 A Sure. 21 Q. Okay. Now, they gave at 200milligrams per kilo 22 gram, Kimbrough and Gaines, enough of this Diazinon at 23 that very high dose level to have induced toxic effects 24 in the mothers, isn't that true? 25 A. Yes, there was some weight loss, among other things BFG08171 161 Dr. Epstein - Cross 1 the mothers showed, 2d Two-out-of-five of them died. 3 A. 4& Yes, there was weight loss and mortality, sure. Under current teratological practice, with the 5 bench people now, as you understand it, don't the S scientists in that field now regard that type of test 7 as not showing teratogenic effects because you are a inducing toxic effects in the mother? 9 A* No. In any teratology experiment you aim to give 10 a series of doses, the top dose being -- the highest 11 dose being a near-toxic-dose, or just short of toxic, 12 very often called MTD, or Maximally Tolerated Dose. 13 That is standard practice. 14 Then you give fractions of those doses. 16 So, it is standard practice, as I said, to have in your 16 high dose, as I said before, doses which approach 17 toxicity. 18 In fact, in the Ciba-Geigy 1981 Study, 19 they had mortality at the high dose and they had also 20 symptoms at the high dose, and I wouldn't criticize 21 the Ciba-Geigy Study on that basis. I think it is a 22 correct and proper approach. 23 Q. 1 am not criticizing the Study. I am asking you 24 whether under current teratological practice, in the 25 experimental fields of teratology, isn't it true that BFG08172 0 C3 0 M O id 0 0 0U 3 d0 6 f-l m 0 id r* 0 O' 43 . > 0 4i c 44 n 0 H V o o 0 c 0 M B 3 o 0 H M O 10 o 0 H 0 C H o 43 O' 0 X 43 >1 4J H >1 43 0 44 c0 H 44 4i 0 01 wo oM M u 0 c 0 1 H B O x; 4i d r| 44 O' 43 rH c H d -H c H O 0 44 *d *d Hn m0 d d d o 0 u 4) d 44 44 3 u H 0 H 6 r| O0 ` 4) 00 4J *0 O 0) c *0 P* Q) bl 4 u 44 id id 0 -H 4) >c3 O d V) 3 H O O' IM O *o X d 0 43 rH o H 0d 44 # d 44 0 o d O 44 3 *0 M rH Q H X o 4J *o c H 0 <M 3m o rl 0 dO 0 0 H N W 0 C o 0 3c 43 0 id 0 (ft M 0 k 3 no 44 4) 3 4X3i >i d 0 *o H 4> X! 0) cn 43 0 0) 0} d c 43 4> o 0 H n id O' 44 O' O 0> H H V 0 4) 44 0 H id 0 43 41 o 43 43 55 10 H 3 d d 0 M 0 00 < *o U N vo id M <u H 44 >i 0) 43 4J c* ! H Pi S3 6 Oo 3 <* u <4 o u 0 M n HI > GO at o 0 0 d 0 u *d d 1 0 u H d 40 H d 0 0 3 44 d 43 44 d 0 d 0 44 H 0 43 44 43 *d Ud o 0 H o * d1 MOd 0 1 *d CO 0 % 0 *d d O' O' rH 0 d d d 43 od 44 *c4 % o 3 o H o 44 H 0u N 0 44 43 0dd00 O' 0 43 0 44 H r. d o >1 44 k O' o U 6 0 0 0 3 44 H O 44 0 < 44 U H 0 44 H H (4 0 d H X M d O' 44 0 d 43 X o 0 0 1 d 43 0 o O 4* 44 * 44 u | rf O' rH *d -M 44 B d0 * 0U 44 O 44 o >1 4) M o 0 3 44 H o* 43 44 0 d d u 44 d do00 d A000000> o 0U rH M 0 0 0 *r 0 0 0 U 0 H O' 0 u a d d d *H 0 M o 44 >1 rH O' 44 6 rH 0 H H H d H H 0 0 0 44 44 d o 3 O 43 u 4 H U H U 0 43 0 > 0 H >0 0X 6 0 3 M H 44 44 C O *M 0 Pi 0 O' M 43 44 O 43 N 0 0 O' *d U >. H 43 *d O *H rH 0 0 44 4* O rH 0 d -H d 44 H O d TJ 3o d O U 0 0 o rH 44 3 0U 0 0 H 0X X 0 0 o 3 d o 0 0 0 d 0 0 43 d 3 43 J3 C 43 o o 44 43 44 d 0 0 4> * 44 43 o > M 44 d 0 44 O' I 0 *d o M 0 H 43 d rf 44 d 43 0 0 44 44 43 H 0 3' & u f) m <0 r* at 8 r to * ,r hi mu ^ft * v 163 Or. Epstein - Cross 1 a teratological effect, but something that is seen in 2 the normal development of rats, and depending upon 3 when you take your sample you may well it, you may well 4 not? 5 A. Oh, certainly. But, it is regarded as a birth a defect. Developmental abnormalities are birth defects. 7 For instance, a cleft lip and a cleft 8 palate, I presume you would regard as birth defect. 9 CL 10 A. Well -- But, they are -- they occur at a stage in preg 11 nancy that the palate and the lip haven't fused. So, 12 therefore, one can't say because that is just simply 13 developmental, therefore, it isn't a birth defect. It 14 is a birth defect. IS ft Well, these rats weren't born, were they, in 16 Kimbrough and Gaines. 17 A. No. The standard practice in most teratological 16 experiments is to deliver the young by cesarean section, 19 the test in the control before birth. 20 ft And, you disagree with me then, I take it, that 21 under current practice in the field of teratology, in 22 experimental teratology, teratologists would not regard 23 a dilated renal pelvis as being a teratological effect. 24 A. I beg your pardon? I am sorry, I was just looking 25 at something else. Would you mind repeating that? BFG08174 164 Dr. Epstein - Cross 1 Cl Then I take it that you disagree under normal 2 present teratological science in the field of experimen 3 teratology, that scientists who found dilated renal 4 Pelvis, hydroureter in a rat, would not accept that as S being a teratological effect. 6& 7 ft a A. No, I think those are teratological effects, You think they are. Yes. 9 ft And you think that is the general opinion in the 10 field? 11 A That is what the authors of the Study considered, 13 and there are numerous statements in the literature 13 attesting to the fact.that on the basis of the Study 14 Diazinon is teratogenic. 15 ft Kimbrough andGaines concluded with a certain 16 qualification, didn't they? 17 A. Certainly. 18 ft They qualified any finding they might have found 19 by saying that it only occurred at toxic level doses? 20 A. Well, that is not entirely true. I share the 31 qualifications of Kimbrough and Gaines, that the Study 22 is not a perfect one, and I pointed that out very 23 clearly and very explicitly in the deposition, that 34 there are criticisms that can be made against the 25 Kimbrough and Gaines Study. However, it is incorrect BFG08175 165 Or. Epstein - Cross 1 to state that the birth defects were only noted at the 2 highest dose level. In fact, as I indicated before, 3 birth defects were noted at the lowest dose level of 4 100 mg per kg where there was no evidence of toxicity 5 at all. And, I explained that very clearly to you 6 before when I said at the 100 milligram per kg dose, 7 that birth defects were noted. 8 Q. Doctor, I would like to read to you from the 9 Study, at page 807 and 808. 10 A. I understand what the authors say. But I am 11 telling you -- you asked me my opinion, and my opinion 12 is that in fact the data in the Study show clearly, 13 and we can go to the data, if you like, by looking at 14 the results of 100 mg per kg, that birth defects were 16 produced. In fact, there was a 12 percent incidence 16 of congenital renal abnormalities at the 100 dose level 17 where there was no toxicity. 18 Q. The people who did the Study, didn't say that. 19 A I answered very clearly that the data show this. 20 The data show very clearly that there were birth defects 21 at the 100 mg per kg where there were no dose levels. 22 One of the things that the evaluator 23 of literature has to do is to read studies, to look 24 at the author's conclusions, and to compare the author's 25 conclusions with the data that they -- which they presen BFG08176 166 Or. Spstein - Cross Now, in general, the authors' conclusion on this are consistent with the data. There is one area in which the authors' conclusions are inconsistent with their own data, and that is the point that 1 have just told you. At the 100 mg per leg -- and, we have been discussing the renal abnormalities for the last four or five minutes, and those occurred at the low-dose level where there was no toxicity. ft So, you disagree with the people who did the Study? A No, I don't. Their data show defects at the 100 mg per kg. There is, however, an inconsistency between one statement in the paper and the results. But, when such inconsistencies occur, you always give precedence and priority to the data. The data are the important things. There are numerous examples in the toxicological literature when p.eople make conclusions that are not justified and that are not warranted by the data. It is the data that are the scientifically sacrosanct elements. The authors' conclusions are interesting, they should be carefully considered, but ( they are not sacrosanct. What is sacrosanct are the data, the scientific data. ft Do you read the journal "Teratology"? A What I do is, I look at the cover of it and find -- BFG08177 167- Dr. Epstein - Cross t pull out any articles that interest me, and l ' do this 2 with about 30 journals, and flip them over about once 3 every since months or so, something along those lines. 4 Q. Are you familiar with the article that appeared in 5 "Teratology" written by Woo and Hoar, which shows their 6 findings that dilated renal pelvis really is not a 7 teratological effect? 8 A. No, I haven't seen this paper. 9 Ql Okay. It would be unfair of me then to ask you 10 questions. 11 Would you agree. Doctor, that many 12 teratologists, in fact most if not all, would feel that 13 it is impossible to extrapolate data from animal studies 14 into man? IS A. Well, no, I would disagree. If this indeed were 16 true, what would be the point of doing -- of the FDA 17 requiring teratology studies on drugs, what would be the 18 point of any requirement for toxicological testing in 19 animals. If this would be the case, why don't we just 20 release all chemicals into the environment, into food, 21 into consumer products, into foods, into drugs, and not 22 bother to do any testing if you cannot extrapolate the 23 results from animal data to humans. 24 Now, it is clear that you can't equate 25 results in animal studies with human risk. You can't BFG08178 168 Dr. Epstein * Cross 1 say because it occurs in one animal that it will 2 necessarily occur in humans. But, all you can say is 3 that there is a probability, or a strong presumption, 4 that this will occur. 5 So, it is not an obligate association. 6 It is a presumption or a strong probability. 7& In fact, in may studies they have shown what 8 happens in animals just doesn't relate to man at all, 9 isn't that true? Did you mention meclizine yesterday? 10 A. Yes. Now, this is not the case. There is a 11 difference between the absence of an effect in the 12 literature, or the absence of data and the absence of 13 an effect. It is true that meclizine, in animals, has 14 clearly been shown to be teratogenic. IS There have been some human studies 16 done on meclizine, and in the human epidemiological 17 literature on meclizine, there is no evidence of 18 teratogenicity. However, as I pointed out yesterday, 19 to develop negative inferences needs very very large 20 populations followed up for long periods of time. And, 21 I have to explain this again by pointing out that with . 22 tobacco it took several decades of research, including 23 many, many millions of people before causal associations 24 could be developed between smoking and lung cancer. 25 Therefore, if one wants to develop inferences as to the BFG08179 169 Dr. Epstein - Cross 1 safety or otherwise in meclizine in human populations, 2 you need very large numbers of pregnant women taking 3 meclizine, some of whom have taken high doses, some 4 of whom who have taken moderate doses, and some of 6 whom have taken low doses, and a vast body of data 6 which you analyzed exclude other exposures before you 7 can develop inferences. a ft Based on that reasoning, Doctor, what is safe? 9 A. Well, toxicology, as best as I indicated, is an to imperfect science. All one tries to do is, one tries 11 to determine by the best type of animal tests whether 12 a material produces adverse effects, whether it be 13 cancer, whether it be birth defects, or what have you, 14 and then arrive at a reasoned extrapolation to humans. 16 Now, if you find these effects in animals 16 there is a suspicion, a probability, a strong suspicion 17 and ignore that information at your peril. 18 If, however, the data are negative, it 19 doesn't mean to say it it safe. It may simply be, you 20 have tested too small numbers of animals. It may well, 21 be that this chemical by itself doesn't produce the 22 adverse effect, but that chemical together with another 23 chemical does. 24 So, like lawyers, scientists do the 28 best they can. And, the best we can do in terms of BFG08180 170 Dr. Epstein * Cross 1 safety is to test thoroughly and extensively in animal 2 tests. If you find a positive, you act on it. And, 3 in some instances -- when I say a positive, there is 4 different degrees of positivity. There may be strongly 5 positive data which very very clearly sound warning 6 signals, or there may be positive data which have 7 less clarity and strength and persistence to them, but 8 which again raise beacons* 9 On the other hand, if the data are 10 negative in a series of studies, then in fact you can 11 say, as far as we know, there is no evidence of hazard. 12 That doesn't mean to say it is safe. And, there are 13 numerous examples in the literature to attest this. 14 0. All right. Now, answer my question, please. IS What is safe to expose a pregnant woman to. 16 A Well, the position which March of Dimes and various 17 other organizations take is that it is rash to expose 18 a woman in pregnancy to any foreign material, to any 19 drug, to any chemical, and with recent evidence which 2D we have even relatively small amounts of alcohol. 21 So, the pregnant woman is an t 22 extraordinarily sensitive -- the growing fetus is 23 extraordinarily sensitive, and it is rash and extreme 24 to expose this highly sensitive collection of growing 2S and dividing cells to the possibility of any toxic BFG08181 171 Or. Epstein - Cross 1 insult. That is as a generalstatement. 2 If you do have evidence that a chemical 3 is teratogenic, or there was a suspicion of its 4 teratogenicity, this becomes all the more clear: Don't 5 do it. Or, if you are considering exposing people, 6 warn them. But, don't do it once you have suggestions 7 in the literature or evidence in the literature, even 8 if this evidence is not watertight. 9& The fact is, the theory or the feeling is that 10 we know so little that virtually anything might do it. 11 A. The consensus of opinion is, it is rash to expose 12 pregnant woment to environmental chemicals, to drugs, 13 to radiation, to any known insult. It is a rash thing 14 to do, even in the absence of data on teratogenicity. IS However, in the presence of data on 16 teratogenicity, this is, to say the least, very, very, 17 very rash. 18 Ql What I am saying is, again, we know so little that 19 our current suggestion is to avoid virtually everything. 20 A. No. You are paraphrasing my answers and 1 have 21 already answered exactly what I mean to say. Ignorance 22 is no excuse for failure to act on available information 23 There is -- there are available data. Act on those 24 available data. 25 The absence of vast amount of other BFG08182 172. Or. Epstein - Cross 1 information is not relevant to public health decisions 2 which have to be based on available information. That 3 is the point. 4& I am not here to ask you to make points you choose 5 to make. I just want an answer to the question. The fact is right now the advice to pregnant women is 7 virtually avoid everything. S A. Avoid all exposures, again, to environmental and 9 toxic chemicals, now much more so to chemicals which 10 are suspected of being teratogenic or which are 11 teratogenic. 12 Qi Doctor, your principal line of work has been in 13 cancer, isn't that correct? 14 A. It has been in a pretty wide-range of areas, rangin 15 from human pathology, X have extensive experience as 15 an M.D. pathologist in hospitals; my experimental work 17 has included a very wide range of areas, including 18 genetic -- tests for genetic effects using pregnant 19 animals; enzyme disturbances from toxic chemicals; the 20 use of protozoa, or single-cell systems for studying 21 cancer chemotherapeutic agents. I have also done exten 22 sive work in cancer, and also extensive research in the 23 whole question effects of chemicals in air, water, food 24 and the workplace. 25 q. Well, then, with such a wide-range, there must be BFG08183 173 Dr. Epstein - Cross 1 certain literature that you relied upon in keeping your 2 self abreast of things. Let me ask you this. There are 3 a few journals in the world that are pretty highly 4 regarded: "New England Journal of Medicine" is one 5 of them, isn't it? 6 A. 7 Q. Yes. "Harvard Medical ` Journal "? 8 A. I am sorry, I missed that. B Ql "Harvard Medical Journal." 10 A. Okay. Fine. 11 Q. "Nature." 12 A. As an ex-Harvard alumnus I would be happy to agree 13 with it, but I am not sure everybody would agree, but -- 14 A. "Nature." Do you think "Nature" is a respected IS journal? 16 A I think -- I must say I have a very high opinion of 17 "Nature," yes. American scientists tend to not have 18 such a high opinion, and tend to like "Science," an IB American equivalent, more. 20 Ql A few years back you wrote a book called the 21 "Politics of Cancer," didn't you? Is that true? 22 A True. 23 Ql And, this was reviewed in an article in "Nature." 24 A Correct. 25 Ql The title of that article was, "Distoring the BFG08184 174 Dr. Epstein - Cross 1 Epidemiology of Cancer, the Need for a More Balanced 2 Overview." 3 A. That's correct. 4& And in that article you were criticized for such S things as distorting scientific evidence? 6A 7 Q. I was accused of that. Statements appear in there that say, "However 8 the political punch is often achieved at the expense 9 of scientific accuracy and balance." 10 A That accusation was made. But, those accusations 11 were refuted by an article of mine published subsequent! 12 in "Nature" which analyzes each one of these charges 13 and in open print demonstrated their untruthfulness 14 and there has not been a rebuttal or criticism of my 15 reply to that article, which was a very long and a 18 very extensive article which appeared in "Nature" in 17 January 15, 1981. 18 Qi So, you took exception to this anyway. 19 A Well, it is not a question of taking exception. 20 It is not a question of personal feelings. My interests 21 are on the underlying scientific data. And, the 22 scientific data were inconsistent with the criticisms 23 of that article. And, I demonstrated this in open 24 print and there has been no criticism or challenge of 25 my very detailed rebuttal of that article. In fact, I BFG08185 175 Dr. Epstein - Cross 1 have had numerous letters and contacts from people + 2 all over the world applauding my response and saying that 3 that article was, to say the least, scientifically 4 misplaced. 5 Qi Nonetheless -- 6 A. The author, incidentally, comes from an institution 7 which is -- which receives overwhelming industry support. S s I am not saying there is any necessary association 9 between the support of the institution and his position, 10 but it is a fact that should be noted. 11 Ql I take it equally then that your position ought to 12 be noted as a fact where you have been waging wars 13 against industry. 14 A. That is a gross misrepresentation of the facts, 18 and I propose to reply to that as you have, I think, 16 made a statement which casts doubt on my professional 17 status. 18 From the late *60's I was consulted 19 by Congress and by government for a wide-range of 20 purposes. Many of these purposes included federal 21 regulations and the development of congresssional k 22 legislation. For this purpose it was necessary to go 23 into industry files and to examine them in great detail. 24 And, in may instances when I did this I was able to 28 document, clearly and precisely, without any question BFG08186 176 Dr. Epstein - Cross 1 of legal challenge, a pattern *of suppression, raanipulati|c 2 and distortion and distruction of data, all of which 3 I have documented in detail in my book, "The Politics 4 of Cancer," which, among other things, has been called S a white collar -- primer on white collar crime. s This book which names names in industry, 7 and which describes events of actual manipulation and 8 suppression, including the fact that industry data is 9 often generated on secrecy in-house -- either the 10 industry's scientists do it -- and, this information is 11 submitted secretly to the regulatory agencies without 12 the opportunity for the scientific community to look 13 at it, and in my book I named various industries and 14 demonstrate what practices they have done, and there 15 has not been a single legal challenge to the specific 16 details of what I have published. In fact, there have 17 been a series of court proceedings which have amply 18 confirmed by position, first of all in asbestos where 19 I have a section known as "The Asbestos Pentagon Papers, 20 which makes it clear that the asbestos industry, as 21 early as 1930, had detailed intimate information on 22 the cancer-causing effects of asbestos and suppressed 23 this information, and invovled in this suppression, 24 this conspiracy, were lawyers, were doctors, were 25 insurance companies, and in fact the record speaks for BFG08187 177 Dr. Epstein - Cross 1 itself, and this has been abundantly attested to in 2 several subsequent litigations since I published the 3 book. 4 Q. Nonetheless -- S A. There is a fine tradition in this country of 6 publishing data -- 7 Q. Well, Doctor, please answer my question. There is 8 no question outstanding. 9 A. I have not completed my answer. There is a fine to tradition in this country of investigative journalism 11 on the one hand and also of publishing the facts and 12 letting facts speak for themselves. And, in the book, 13 "The Politics of Cancer," besides having a detailed 14 scientific analysis of many causes of cancer, there 16 is abundant documentation of improper practices by 16 the chemical-pesticide industry, the pharmaceutical 17 industry, in actions relating to the improper handling 18 of information and data; either the generation or the 19 interpretation of the data. 20 Ql Okay. Essentially, what that document is though 21 is a political document, isn't it? k 22 A I don't know what you mean by political document. 23 "The Politics of Cancer," which is referred to by many 24 people now as the "The Silent Spring of Cancer," is a 25 scientifically precise -- BFG08188 178. 1 Dr. Epstein - Cross HR. HcCANDLESS: Your Honor, I would 2 ask to terminate this answer. 3 He originally stated -- 4 A. It is a scientifically precise -- 5 THE COURT: Mr. McCandless, when you 6 ask questions like that, you encourage answers like this. 7 HR. HcCANDLESS: I got an answer. 8 THE COURT: None of which has anything 9 to do with the issues before this jury. 10 HR. McCANDLESS: I understand that. 11 I was about to ask -- 12 THE COURT: So, if you will go on to 13 the next question and avoid that kind of question we 14 won't have to listen to these extended lectures. 15 MR. McCANDLESS: Yes, your Honor. I 16 thought we had received an answer when he said he 17 didn't know what I meant. But then somehow from not 18 knowing we appeared to be going down the road. 19 BY MR. MCCANDLESS: 20 Ql Okay, Doctor, that's all I have. Thank you. 21 A Thank you 22 23 Honor? 24 25 MR. BOLDEN:. May I have a moment, your (Pause) (Off-the-record discussion among BFG08189 179 Dr. Epstein - Cross 1 plaintiffs' counsel.) 2 MR. BOLDEN: No questions, your Honor. 3 THE COURT: You may step down, Doctor. 4 MR. GRIFFIN: If your Honor please, S based on the examination by Mr. McCandless, I have 6 just a couple of questions. 7 THE COURT: All right. 8 MR. BOLDEN: I will object to that, 9 your Honor. 10 THE COURT: No. He has a right to 11 cross-examine further after the other cross-examination, 12 if he wishes. 13 MR. GRIFFIN: I think it will be very 14 short, your Honor. 16 FURTHER CROSS-EXAMINATION 16 BY MR, GRIFFIN: 17 Qi Dr. Epstein, in answer to some questions Mr. 18 McCandless asked you, you said Ciba had patented 19 Diazinon back in the mid-fifties. 20 A Well, it may be a mistake. They developed it. 21 They developed it right about '51 and marketed it arounc 22 about *54. But -- 23 Q. Well, you know if there was a patent, it only 24 lasts for 17 years anyhow, don't you? 25 A Yes BFG08190 180` Dr. Epstein - Cross 1 Q. So, that by the mid-seventies, this was a product 2 that could be produced around the world without any 3 limitations by anybody who wanted to produce it. 4 A. Z take your word for that. 6 Ql Now, Doctor, I have had a chance over the evening 6 to look at those other references you have# And, if 7 there is anything in there you really think is important a I don't want to hold you back from telling the jury 9 about it. 10 A. n Well, I don't want to be -THE COURT: He has now withdraw his 12 objection to your reference to the -- is it the subse 13 quent studies and articles? 14 MR. GRIFFIN: Yes, sir. He had three 16 references yesterday I knew nothing about, and over the 16 evening I was able to look at them, and if the Doctor 17 thinks they are important and the jury should know about 18 them, you can tell them. 19 MR. BOLDEN: I think that is unfair. 20 We were not permitted to question the witness in direct 21 examination about them. 22 23 nity . 24 THE COURT: You will have full opportu If you wish now to inquire, I will do 25 that before he resumes his cross-examination. BFG08191 181 1 Dr* Epstein - Cross MR. BOLDEN: No, your Honor. I think 2 it is probably best if Dr. Epstein wants to refer to 3 it, to let Mr. Griffin conduct the examination. 4 THE COURT: All right, you may bring 8 it out and you may, in your redirect examination, which 8 you have a full right to do, then explore it as fully 7 as you wish. 8 Mr. Griffin, you may proceed. 9 BY MR. GRIFFIN: 10 Q. Doctor, I can just short cut it. Doctor, by saying, T1 you had three additional references. One had to do with 12 egg and chick studies, didn't it? 13 A Are we talking about one chart, or all my charts? 14 Are you withdrawing your objection to all my charts, IS or are you being selective about what I can -- 16 Q, i was talking about the literature references. 17 That is the only thing I have been able to check. IB A Well, there are several literature references, 19 and essentially what are you saying, that I can refer 20 to all three charts, or would you like me to be 21 selective about my suppression of information? 22 & I may have misunderstood you. I only thought there 23 was three additional literature sources to which you 24 went in making up the chart. 2S A In one particular chart, on the chart on the BFG08192 182. Or. Epstein - Cross 1 teratogenicity of Diazinon, that is true. There are 2 however, also statements on quotations from the 3 literature on precautions to be taken with Diazinon and 4 persistence with Diazinon, and quotations si the 9 literature on teratogenicity of Diazinon. 8 Mow, essentially what are you telling 7 me you want me to do? Should X suppress some informatici 8 all information or no information? 9 Qi Doctor, I simply want to give you a chance to tell 10 the jury if there is anything in all of that that you 11 consider particularly important on this question of 12 whether in fact, whether in fact, there is a teratogenic 13 effect in Diazinon demonstrated in animals. 14 JL X see. So you are being selective about what 18 aspects I can inform -- discuss with the jury. 16 To be quite frank, I must be guided by 17 the Court on this -- 18 THE COURT: No, no, no. Mr. Griffin's 19 question, whether he intends it or not, eliminates all 20 restrictions 21 THE WITNESS: Thank you, sir. 22 THE COURT: You may now answer to your 23 heart's content and disclose to the jury all that which 24 you have said up to this point you have been bound not 25 to disclose. BFG08193 183 Dr. Epstein - Cross t THE WITNESS: -Thank you, your Honor. 2 I will return almost immediately. I just want to -- 3 (The witness withdrew from the witness 4 stand and approached the easel.) 5 A. May I have a red pen, please? Again. 8 (A red pen was handed to the witness.) 7 First of all, let me say I appreciate 8 this change of position which I think would be helpful 9 in presenting my thoughts on this matter. 10 The first chart is on the teratogenicity 11 of Diazinon. It is a summary of data which 1 am aware 12 of in the literature. 13 This involves certain studies involving 14 eight different species of animals. 15 I have made changes here to reflect 16 my present evaluation of the data. And, as you see 17 that in eight-of-the-thirteen studies, Diazinon was 18 shown to be teratogenic. 19 As was made clear yesterday, there are 20 some discrepancies between these results and the results 21 which I discussed at the time of the deposition, and the 22 reason for this -- X would like you to be clear of the 23 reasons for the discrepancies is that while X did have 24 a great deal of information in my files at the time of 25 the deposition, I hadn't reviewed it all. And, in fact. BFG08194 184 Dr. Epstein - Cross 1 if you look at the very first.two studies, the duck egg 2 and the chick eggi at the time of my deposition I said 3 they were negative. The reason for that being is in 4 the original study described by the author, Khera and 5 Lyons, in which eggs were injected with Diazinon, there e was no reference at all to teratogenicity to defects 7 and abnormalities. And, I took the position that in 8 the absence of this, it means there is nothing there. 9 However, in more recent review of the 10 literature, including material which I offered counsel 11 for the defense at the time of the deposition, I found 12 an abstract written by Khera, the first author there, 13 which states very clearly that Diazinon was teratogenic. 14 Similarly, if you look at the two bottorc 18 -- the two studies at the bottom by Earle, the pig and 16 the dog, I had previously said that the results in the 17 dog were equivocal, and I now have changed that to the 18 results in the dog are positive, not equivocal. And, 19 the reason for this being is that I had in my file an 20 abstract which I hadn't read, again by Earle, which 21 points out that in the dog Diazinon was clearly 22 teratogenic. So, that is the first chart. 23 (Witness withdrew from the witness stand 24 and presented another chart to the jury.) 26 So, in other words, in BFG08195 185. Dr. Epstein - Cross 1 aight-out-of-thirteen studies .involving five species, 2 different studies, Diazinon was shown to be teratogenic. 3 Now, X had made clear yesterday that 4 some of these studies are better than others, none of S them are entirely perfect. In fact, some of them have 6 major defects. But, the studies in the aggregate, creat 7 at least a probability of Diazinon being teratogenic, 8 if not a strong suspicion. 9 Now, let us leave my evaluation alone. 10 Let us assume that you haven't heard my evaluation for 11 the moment, and let's see what the literature says on 12 the teratogenicity of Diazinon. Let's see what are the 13 statements in the literature on the teratogenicity of 14 Diazinon which could have allowed the development of 18 an opinion as to whether this was teratogenic, or 16 suspected to be teratogenic, or probably teratogenic. 17 Now, here I have a series of quotations from literature, 18 including some authors of some of the previous studies. 19 Now, the very first study was by Khera. 20 This is based on the Khera and Lyons first study which 21 X told you the abstract makes it clear that Diazinon 22 is teratogenic. 23 The statement in the literature reads 24 that Diazinon induced -- and X quote, and there is 25 quotations marks, "congenital foot deformities," in eggs BFG08196 186 Dr. Epstein - Cross 1 in duck and chick eggs. "Congenital foot deformities" 2 is in quotes. 3 The next is the Kimbrough and Gaines 4 Study. "Diazinon produced some malformation." 5 Kimbrough and Gaines go on to say, and 6 I haven't written that down there, "The spontaneous 7 incidence of these malformations is very low in the 8 control strain of rats." 9 So, it produced malformations, and the 10 incidence of these is very low in the untreated 11 controls. 12 The next is the Study by Green in which 13 it says, "Diazinon produced teratogenic activity in 14 all chicks." 15 The next is the Earle Study, and, -- 16 incidentally, I should point out, underneath Khera, it 17 says, "Canadian FDA," Canadian Food and Drug Administra 18 tion, "CDC," Center for Disease. Control -- that is a 19 big federal research center in Atlanta, which has major j 20 responsibility in birth defects and congenital abnor 21 malities; that Earle came from the Food and Drug 22 Administration. 23 Nishimura is the next author, a Japanese 24 author, who says, "The following chemicals were proved 25 to have a teratogenic effect: Diazinon." BFG08197 187 1 Dr. Epstein Cross The next is NZOSH, National Institute 2 for Occupational Safety and Health, the official 3 government agency that makes recommendations to the 4 Department of Labor on standards governing exposure of S workers to toxic and chemical -- adverse agents in the 6 environment. And, it reads, "Based on available 7 evidence -- Diazinon -- can be considered possibly 8 teratogenic and should be handled with caution by women 9 of childbearing age." 10 The next, Sax, a standard textbook of 11 industrial toxicolgoy, refers to Diazinon as "an 12 exper." -- exper. is an abbreviation in the text, short 13 for experitmental -- "an exper. teratogen." 14 The final is NIOSH, RTECS. RTECS is 15 Registry of Toxic Effects of Chemical Substances, which 16 in 1977 -- and this lists detailed accounts of toxic 17 effects of a wide-range of almost 50,000 chemicals are 18 listed in these registries. And, in the year 1977 and 19 1978, 1979 and 1980, Diazinon is listed as a teratogen. 20 I regret that I haven't checked the 21 1981 and the 19- -- I don't think the 1982 version is 22 out, but there you are. 23 Could I have the next, please? 24 (Another chart on the easel is being 25 presented to the jury.) i ( ( BFG08198 188 Dr. Epstein - Cross 1 The final chart relates to quotations 2 from the literature on precautions to be taken with 3 Diazinon, and whether or not -- and what is the 4 persistence of Diazinon. 5 Now, the first first statement comes 6 from Menzie in 1969, and Menzie is USI, that is short 7 for United States Department of Interior, 8 ft Excuse me. Dr. Epstein. It is true, isn't it, 9 whatever you are quoting here has nothing to do with 10 the teratogenic effects? 11 A. Not in the slightest. It has everything to do with 12 it, because if indeed there is no exposure to Diazinon 13 then my interest in Diazinon as a possible teratogen 14 ceases. So, this is very relevant to the question. 15 Ci This goes to the issue of exposure? 16 A. -- of the -- the problem of the birth defect rests 17 on two issues. One, is the agent teratogenic, and was 18 there exposure. This speaks to the exposure aspects, 19 and in fact, you never consider teratogenesis under 20 any circumstances unless you take into account two 21 facts, namely: the effect on the experimental system, . 22 and the question of human exposure. 23 ft And, did you gather in the course of gathering 24 these quotations, anything from those authorities which 25 said what the exposure level should be or could be? BFG08199 189 Or. Epstein - Cross 1 A. Well, would you let me finish and then 1 -- 2 Q. I want to know whether you did. 3A Yes. I will be very happy to respond to any 4 questions if you will allow me to finish. 5 Q. Go on 6 A. Menzie, 1969, United States Department of 7 Interior, quotation: "Diazinon half-life varies from 8 21.6 to 80.2 days." 9 Now, what this amounts to -- let me 10 explain,if I may, what a half-life means. A half-life 11 is the standard way of expressing the time taken for 12 material to degrade and to disappear. 13 If you say the half-life of a chemical 14 say, in soil, is four days, it means by four days IS 50 percent of that chemical will have disappeared, okay? 16 Four days after that, another 50 percent would have 17 disappeared. So, in other words, by eight days there 18 would only be 25 percent of the original. So, half-life 19 is an expression of how long it takes for half the stuff 20 to disappear. 21 Now, in soil, the half-life of Diazinon 22 can extend up to nearly three months. 23 Now, take into account that in soil you 24 have air movement, constant air movement? wind, sun, 25 rain and bacteria that are breaking down the Diazinon. BFG08200 190 Dr. Epstein - Cross 1 Very very different from the situation in a house, or 2 in a carpet where you don't have constant wind movement, 3 air movement; you don't have constant wind, you don't 4 have constant sun, you don't have light, you don't have S bacteria which break the stuff down. 6 So, the statement already -- by 1969 7 it was known that Diazinon was a relatively stable 8 material, that it could vary up to three -- almost three 9 months, eight days. By eighty days, only half the stuff 10 would have disappeared. Okay. 11 Now, let's see what the industry says 12 about Diazinon -- about exposure to Diazinon. This is 13 a statement from a book by Cornwell, a British textbook 14 by a manufacturer, director of a pesticide group known 15 as Rentokil. And it says, "...inhalation should be 10 prevented in confined areas." 17 The next, Ciba-Geigy, 1975; the 18 literature of Ciba-Geigy. "Do not breathe spray mist. 19 Do not get in eyes or skin or clothing." "One half of 20 the original application (in soil) was lost in two to 21 four weeks." Now, this is quite interesting. 22 Ciba-Geigy, in 1975 says, about two 23 to four weeks, up to four weeks, the half-life of 24 Diazinon is up to four weeks. it is interesting that 25 the same Ciba-Geigy statement that says that, also has BFG08201 191 Dr. Epstein - Cross 1 a reference to the authority on which this is based. 2 This statement is based on an author known as 3 Braugh Rasmussen, which is cited in the Ciba-Geigy 4 document. But, Ciba-Geigy states that one-half was 5 lost in two to four weeks. It doesnft say one-half 6 was lost in eighty days. But, be that as it may -- 7 even though the Ciba-Geigy document says that, half 8 the stuff can remain after four weeks, okay. 9 The Environmental Protection Agency, 10 Allison and Hermanutz. What do they say? This is a 11 study in water. "Diazinon may persist many months in 12 some fresh water environments." Again, with exposure 13 to air, to sun, constant air movement; not just a 10 14 or 20 percent loss, or what have you, but constant air 15 movements, bacteria even can exist for many months. 16 Now, the United States Army, in Fort 17 Detrick, the Center for Bacteriological Warfare Research 18 -- and, there is a paper in 1978 by a man called Meier, 19 who determined that there was an impurity in Diazinon, 20 a highly toxic impurity known as sulfotep, which is 21 highly persistent, very stable and highly toxic, and he 22 noted that this information was known to Ciba-Geigy and 23 that Ciba-Geigy had failed to warn people on its label, 24 and had failed to produce any information in the open 25 scientific literature, or its own literature on sulfotep, BFG08202 192 Dr. Epstein - Cross 1 it's highly toxic, highly persistent impurity. And, 2 I quote, "Sulfotep is an impurity common to all 3 formulations. It is much more toxic. It is not more 4 stable. It may concentrate. Sulfotep presents a 5 previously unidentified potential hazard to healthy" 6 No warning by Ciba in its literature, no reference in 7 the total scientific literature. 8 NIOSH, 1978, National Institute of 9 Occupational Safety and Health, 1978: "Diazinon can 10 be considered to be possibly teratogenic and should be 11 handled with caution by women of childbearing age." 12 Baselt, in 1978. Dr. Baselt is the 13 Connecticut Medical Examiner who, I don't know, but I 14 am told has extensive experience in poisonings and 15 pesticides and other agents: "Diazinon itself 16 and I quote, "-- accumulates in fat at concentrations 17 over 100 times those in blood." 18 So, in other words, even when you look 19 in blood, say about a few days afterwards, a few days 20 after a pesticide spraying, you find no diazinon in 21 the blood, but, it is accumulated in the fat. 22 And, he goes on to point out that a 23 particular breakdown product, some breakdown products 24 of Diazinon, which I will tell you what they chemical 25 is, but it doesn't make any difference -- BFG08203 193 Dr. Epstein - Cross 1 diethylphosphoric acid -- end, the metabolites were 2 found in urine specimens collected 23 and 58 days after 3 exposure. So, two months after exposure you could still 4 find metabolites of the Diazinon in the body. S Now, I don't know how many of these 8 metabolites, or which of these metabolites are terato 7 genic. I have come across no information on the 8 teratogenicity of some of the metabolites. But, the 9 fact remains that the Diazinon persists in the fat, 10 and even as long as two months after exposure you can 11 demonstrate metabolites of Diazinon in the body. 12 Thank you. I appreciate the opportunity 13 you gave me. 14 0 All right. Doctor. Now, as far as the talk on 15 all the labels that you have given us, is the purpose 16 of that to get the jury mad at Ciba? 17 A No. I think the purpose very simply is the 18 following: The purpose is, as I indicated before, in 19 an analysis of any adverse effect, one needs to have 20 two pieces of information. One, information on the 21 inherent toxicity of the material, which in this case 4 22 was the experimental teratogenicity; the second is 23 information on exposure. 24 As far as information on exposure is 25 concerned, one needs to know, does the material break BFG08204 194 Dr. Epstein - Cross 1 down immediately; is it persistent; does it degrade, 2 and information of this kind. And, this, 1 submit, is 3 highly relevant to the question of the persistence 4 and exposure. 5 Now, I am sorry if you take a different 6 opinion, but in my view this is critical to an analysis 7 of the problem. 8 ft Let me just ask you: This case doesn't involve 9 in any way Diazinon in the soil, does it? 10 A. Certainly not. But, Diazinon in the soil breaks 11 down -- 12 & Excuse me. Doctor -- 13 A. Excuse me. Diazinon in the soil breaks down -- 14 & Doctor -- 15 THE COURT: Dr. Epstein -- 16 THE WITNESS: I am sorry. 17 Ci Just answer my question and we will get over this 18 quickly. This case doesn't involve Diazinon in the 19 soil. 20 A. Correct. 21 & This case does not involve Diazinon in water. 22 A. Correct. 23 0. Did you make any searches through the literature 24 to see what the breakdown of Diazinon would be in the 25 environment that we are talking about? BFG08205 195 Dr. Epstein Cross 1A To be quite frank, this is an issue that came -- 2 that arose -- 3 ft 4 A. 5 Did you make any-searches to see -- No. This is an issue that only arose 6 relatively recently. I had already -- at the time of 7 edition I was aware of the Ciba-Geigy statement. The 8 other references are more recent ones. As I was told, 9 the questions of exposure have cropped up. But, there 10 is a Ciba-Geigy study which I would like to refer to, 11 if I may -- 12 ft Doctor, I don't want you to get into that. 13 Answer my questions, and if you and your counsel want 14 to bring something up, bring it up, all right? IS A. Yes. 16 ft Just -- 17 A The answer is yes. 18 ft Just answer the few questions X have so X can 19 get over this recross. 20 You have already said that you do not 21 know what effect there might be if such Diazinon is 22 found in the blood after a period of time. 23 A What X said was, X don't know -- I am unaware of 24 information on the teratological effects of the 25 metabolites of Dia2inon. BFG08206 196 Dr. Epstein - Cross 1 They would not be in the blood. I 2 think it is unlikely -- it disappears from blood 3 fairly rapidly. It would be in.the fat in the body. 4 Qi Mow, if you will go back to the charts with the 5 quotations that you had in what you call the various 6 studies. 7 A. Sure S Cl In your studies we have Khera -- and that was a 0 Study involving eggs, correct? 10 A. Yes. Do you want the quotations from the 11 literature? 12 Ci No. I want to find out what the studies were 13 about. I will ask you just a few questions about it. 14 Khera was about eggs, correct? 16 A Well, there were two studies by Khera. One was 16 on duck eggs and the other was on chick eggs. 17 Q. All right. Duck eggs and chick eggs. And, you 18 and I talked about the significance of those yesterday. 18 A Correct. 20 Ci All right. 21 Then, Kimbrough and Gaines -- 22 & Well, excuse me. You have left out a couple. 23 The Green Study and the Procter Study 24 are both on chick eggs. 26 Q> I was going to come to them. I listed them in the BFG08207 197 Or. Epstein - Cross 1 order you presented them. 2 A. I am sorry. I beg your pardon. 3 Q. Kimbrough and Gaines, Mr. McCandless talked to 4 you about them, and you have discussed them. 5 A. Sure. 6 Ql 7 8 A. Right. Correct. Then Green wasalsoone egg. 9& 10 A. Earle was on a dog and a pig or pigs and dogs? Correct. 11 Ql Mow, Nishimura, in Japan, that was not a Study at 12 all. 13 A. No, that's right. That was quotations from the 14 literature. This is headed, "Quotations From 15 Literature." 16 Ql And, so far as you know, Nishimura was simply going 17 back to Kimbrough and Gaines. 18 A I am not sureexactly what hebased his opinion 19 on, but he expressed that position that it was 20 teratogenic 21 Ql Well, if he had studied the world literature, as 22 far as you know, because you have studied the world 23 literature, you would have to go back to a study. So, 24 you would have either Kimbrough and Gaines or Earle, 25 those are the only two studies -- BFG08208 198 Dr. Epstein - Cross 1 IL It is pretty likely, but! honestly don't recall 2 exactly what he based it on. 3 Qi But, you don't have any other basis for judging 4 what he based it on. 5 IL no, that's right. It was a review of the 6 literature 7 Ql It was just a literature review. 8 IL That's right. 9& Also, when he used the word -- was it, "proved" to 10 be? 11 He states, "The following chemicals were proved to 12 have a teratogenic effect." 13 Q, All right. Now, "proved," do you know whether that 14 was the word he used, or wasn't? 15 A 16 Q. God knows, my Japanese is pretty poor. Hell, there are actually a hundred different 17 Japanese languages, aren't there? Dialects? 18 A I am more than prepared to concede that there are 19 infinite subtleties in the Japanese language. 20 Ql And he could just as well have said, reading the 21 articles you can see the author's claim and you don't 22 know how somebody translated it? 23 A No argument. 24 Ql 25 All right. Now, the NIOSH Report, the first BFG08209 199 Or. Epstein - Cross 1 NIOSH Report, that simply references Kimbrough and 2 Gaines, doesn't it? 3 A. Correct. And a reference which was looked at by 4 -- and a statement which was looked at by a wide-range 5 of reviewers, governmental reviewers, industry reviewers, 6 professional groups; a wide-range of people. 7 Q. But, all it references, the only study it refers 8 to is the Kimbrough and Gaines Study. 9 A. You are correct, sir. 10 Q. All right. Then, the Sax book you talked about, 11 it says, "experimental teratogen." And it has a 12 reference. 13 A 14 fr Correct. And, the only reference it referenced is NXOSB. 15 A Correct. 18 Q, So again, you're referenced backto Kimbrough 17 and Gaines. 18 A That's right. 19 Ci And then the final NXOSH statement you had was 20 simply a repetition of the earlier NIOSH. 21 A That's correct. i 22 q. So, as far as all this learning is concerned, 23 what you've got is Kimbrough and Gaines and Earle. 24 A What you have is statements in the literature 25 expressing the position that Diazinon is teratogenic. BFG08210 200 Dr. Epstein - Cross 1 The basis for this rests on a .relatively small number 2 of studies. As I indicated before, in eight-out-of- 3 thirteen studies Diazinon was shown to be teratogenic, 4 ft Doctor, I just want to make sure I have this clear 5 now. 6 A. 7 ft I think you have. Except for eggs -- we discussed eggs yesterday. 8 Except for eggs, the only studies that you can put 9 a finger on having to do with -- where you can even 10 put a plus, are Kimbrough and Gaines and Earle, as 11 far as animal studies. 12 A. Not correct, sir, notcorrect, 13 ft 14 A. No? No. IS ft Dobbins. 16 A. The studies, fine, 17 ft Dobbins. 18 A. Dobbins, in the Wistar strain of rats, Kimbrough 19 and Gaines in a different strain of rats, were 20 remarkably similar congenital abnormalities; Earle, in 21 6 pig, pigs, which are not very often used in these t 22 studies and Earle in a dog. So, we have a pig, dog, 23 two strains of rats, quite apart from chick eggs and 24 duck eggs. 25 ft To the extent that you know the literature and you BFG08211 201 Dr. Epstein - Cross 1 know other studies, everything else is negative. 2 A. Well, as I indicated, there are one, two, three, 3 four -- one, two, three, four, five negative studies. 4 Q. All right. 8 Now, Messrs. Kimbrough and Gaines, 6 they are not teratologists, are they? 7A Well, I would say that they are toxicologists, 8 not primarily teratologists. I would say that is 9 correct. But, I would say they have substantial to experience in translating toxocological data into It areas of human risk. 12 Ql And, Dobbins was a medical student, wasn't he? 13 A To be quite frank, I am not sure. 14 & All right. All right, sir, that's all I have 18 in addition. 16 17 REDIRECT EXAMINATION: 18 BY MR. BOLDEN: 19 Q. Just one question. Of the five negative studies 20 you referred to, you said there were thirteen studies, 21 eight positive and five were negative. 22 A Right. 23 Ql Of the five negative studies, how many of them 24 if any, are Ciba-Geigy studies? 25 A Well, if by Ciba-Geigy studies you mean studies - BFG08212 -0 P P * 0 0 00c c H 0 o *d V 3 k P >1 o 0 d M 3 >1 P d tP to 0 -H p 0 0P u o O H 0 Du P u a0P -H oP 0 TJ H 0 0U OS 0 H 0 00 1 N > P CP I7' tr 0 r-4 a r| p H V 0 c 0 OO 0 o P 0 1 0 I 0 >f-i 0 fL A P W H H 44 1 fOfi 4 OU 0 1 p 3n P PPp O 3 Q oO 0P 44 M 44 H to oP 0 *3 1 uP 00 6 uP oO 44 44 o0 m p 0 *, P 0 r- P 0 M 0 0 0 P Ok r-i 0* tu 3 o 0 . N pPP N 1 0 H O 3P u r* <* H H tu M 0 P P P 3 44 o 2 3 O >i 3 0 P H # 2 W Q J O tt 4 PH 2 0 3 O H P 0 0 3 d* s no -* 00 3 H 44 O M o a 1 O M 0P p 0P p p H 0 M 0 0U O >1 p> PH 44 0 44 d >1 O H 0 30 H 0p P 0 r. P Pp 0 d >i P 0 0 H P P 3 0 *d tr 0 p P i 0H r. d 0 0 3uM 3u 00 3 3P O d -rl 3u o P u 3 O r| P 3 44 P p 0 0 O 0P 0P 0 >i P pP 3 P o PP 0* 00 0 0 0 0> P 3P u 0 *. 0 P 0 0 P 3 -rl P 0P pP 0 -H O TJ M p 0 3 P U M 0 o O' r4 O O d >i P 30 0> > 'd 0 P 33 p3 r p 2 PP 0 t> M O 0 00 P 0 3U O M H P 0P 0 3 O 0p - O TJ *d P E- * >H *d 03 P * >1 H 0 0 3 H 22 tn O p H M rt P 3 s* fe 0 0 0 UP0 5 PP P 0 0 HPP 3 4, IP O XH 0 d 03 >P P oO 3 % > w PH 0 -H 0 rH iH I U P *d o. 0 d rH >i r-l 0 to to 0 *H U 3 P 0 d P H 53 0 2 P P 0 2 P < o p; PH 2 o 03s rl tn 0 H 0 r-t r-f w 5 > P C* P >1 0 pO 0 rl >i c* 4 eft n n * D o r 9 CM o o-- n w * m 0 r to O 8N V, > Ml HM *r *** ,, ' 203 Dr. -pstein - Recross 1 MR. BOLDEN: Thank you. 2 THE COURT: All right, anything more? 3 MR. MCCANDLESS: No. 4 THE COURT: Thank you. You may step 5 down. Dr. Epstein. 6 We will take a ten-minute recess. 7 THE WITNESS: Thank you. 8 (Witness excused.) 9 (Court recessed.) 10 11 12 13 14 18 16 17 18 19 20 21 22 23 24 28 BFG08214 204 1 2 December 9, 1982 3 December 10, 1982 4 I N D E'X Page 2 Page 147 S 6 WITNESS DIRECT CROSS REDIRECT RECROSS 7 Dr. Samuel Epstein By Mr. Griffin 2 201 64 202 a By Mr. McCandless - 134 -- -- 9 10 11 12 13 14 IS 16 tl IS 19 20 21 22 23 24 25 BFG08215