Document ZBYxxrnYk5znmb47Dd7dpQeaY

1 IN THE UNITED STATES DISTRICT COURT 2 FOR THE WESTERN DISTRICT OF TE, NESSEZ 3 EASTERN DIVISION 4 5 6 WOODROW STERLINGp at alp 7 Plaintiffs, 8 Vs . 9 VELSICOL CHEMICAL CORPORATION* 10 Defendant . 11 ) . 78-1100 12 13 14 15 TRANSCRIPT OF THE EVIDE 16 VOLUME LVIII 17 SEPTEMBER 20, 1983 18 19 20 21 22 23 24 25 )7 8690 1 IN0EX 2 DIRECT 3 Raymond D . Harbison 4 8693 5 9830 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 CR( 87! 0793 8821 $816 1 2 3 4 497 5 499 6 Soo 7 501 8 502 9 503 10 504 11 505 12 506 13 507 14 276 15 Soo 16 17 18 19 20 21 22 23 24 25 EXHI BITS IDENTIFICATION 8747 8756 8758 8762 8763 8764 8778 8786 8812 $861 8691 EVIDENCE 8750 8756 8758 9762 8763 8764 8783 8790 8825 8828 8692 1 TUESDAY MORNING 2 SEPTEMBER 20t 1983 3 4 The trial of this case resumed n this date, 5 Tuesday# September 20p 1983f at 914o o* lock a .m ., 6 when and where evidence was introduced nd proceedings 7 had as followas 8 9 THE COURTs I have said go d morning, 70 everybody, so long, and it is in the record 11 so many times, that I am just oing to say 12 good morning . 13 ?HZ LAWTERSt Good mornin 14 THE COURTs All right, Mr . Gentry . 15 MR . GENTRYz Thank you, Y ur Honor . 16 This morning we have a witness who was cn 17 briefly before the Court in Ja uaryo He has 18 boon sworn . I will call him t the stand . 19 Dr . Harbison . 20 21 22 23 24 25 8693 9~ .:Z'o - 9-3 RAYMOND D . HARBISONs 2 having been previously sworne was exami 3 testified further an follows : 4 and 5 DIRECT EXAMINATION BY MR, GENTRY : 6 MR . GENTRY : If the Court pleasest 7 we will voir dire Dr . Harbison on other 8 areas of expertise other than that which 9 he was qualified in Januaryt which was 10 toxicology . 11 THE COURTs All right, sir . 12 MR . GENTRYs He in also, we believe, 13 an export in other areas . I would proffer 14 his previous CV to the Court . 15 Dr . Harbison, it has been quite some time since 16 you were on the stand before . Tell us your full na=e, 17 if you will, please# and where you live? 18 A, My name is Raymond D . Harbison, and I live 19 in Little Rock . 20 QO W*hRve previously established that one of 21 your disciplines is toxicology . Toll us a little bit 22 about that . Where are you an a toxicologist? 23 A . I am the Director of the Division of Inner- 24 Disciplinary Toxicology at the Univerx ty of Arkansas 25 School for the medical Sciences, and I am in the Inner- 9694 1 Disciplinary Toxicology Program between the medical 2 science campus and the National Center -or Toxicology 3 Research . 4 What is the National Center for Toxicological 5 Research? 6 A. The National Center is a Congra3sionally 7 mandated facility, which was establishe approximately 8 ton years ago* and the purpose of the N tional Center 9 is to conduct mission oriented research in the area 10 of toxicology to resolve or solve natic al problems 11 that arise regarding chemicals, drugs and other sub- 12 stances* 13 Q . Tell me how that works as a practical matter7 14 Tell me what questions you are asked, where are you 13 asked, where the questions come from, who generates 16 the questions? )7 A . The questions can be generated by Congresso by 18 the National Institutes of Healthg by he National 19 Toxicology Program# and the questions hat would be 20 asked are is the substance a cancer-ca sing agent, or 21 might it have a potential for causing irth defects, 22 or might it be a mutagenic material or what the inhereal 23 toxicological properties of the matori I might be . 24 Q . Are the national laboratories o which you are 25 referring and the laboratories of the niversity of 3695 1 Arkansas School of Toxicology the same aboratories? 2 A* Well, they are physically separ ted, and, not 3 they are not the same laboratories . Th y are 4 different . 5 Q. You wear two hats then? 6 A, That is correct . 7 Q. Let's talk in terms of the Univ rsity School 8 of Toxicology first . What kind of proq ams do you 9 have at that particular school? 10 A* The toxicology program at the niversity 11 serves several functions . one of our issions is 12 education . We have a graduate trainin pcogram in 13 which we have about fifteen to twenty tudents who 14 are seeking degrees in toxicology . 15 0 . Are those doctoral degrees or omething less 16 than that? 17 Am They would be a person seeking a doctoral 18 degree . 19 We also serve the educational unction of 20 training physicians in the area of tox cology, and we 21 also serve an a consulting function fo the personnel 22 of the nedical center in cases where t ere might be 23 suspicion of poisoning or unusual inci ences in which 24 there might be some need to have extra information 25 or a resource to help treat these P tilints . 8696 1 Q. Thi3 is at tho universizy as opp sed to the 2 National Laboratory? 3 A. 4 Q. That is correct . Do you serve the EPA at the Uni ersity? 5 A. Yes, I do . 6 Q. In what manner? 7 A, At the University I run a medic 1 monitoring 8 program for the United States Environme tal Protection 9 Agency, and I also provide a tachnica! oxicoloqical 10 report service for the agency, for its ontzactors 11 who are involved nationally in the inve tigation of 72 hazardous waste sites, and the way it w rks is 13 that we perform pro-employment examinations on the 14 hazardous waste site workers . lie also do an annual is surveillance of hazardous waste site w rkers, and we 16 provide toxicological information when it is needed 17 for the investigation of the sites or or any problems 18 that might arise regarding chemical co tamination of T9 personnel who are involved in waste si a investigation* 20 0 . As head of the School of Toxicilogy at the 21 University of Arkansas medical Schoole do you or do 22 you not teach mad students? 23 A* Yes, I do teach medical studen .s . 24 Q* What do you teach them? 25 At I teach them the basic principles and concepts $697 of toxicology . I teach them about chen cals and the 2 effects that chemicals can have and gen rally prepare 3 them for the diagnosis, treatment and m nagement of 4 any chemicals which might induce some a lment . 5 0. 1 want to digress one minute . u have already 6 testified to this, but briefly give us ur educational 7 background? 8 A, I received a Doctorate in Tox at the 9 University of Iowa in 1969 . Prior to t, in 1965 10 I received a Bachelor of Science Degre in Pharmacy 11 from Drake University . I subsequently an hired by 12 Tulane Medical School, where I was on a f aculty 13 from 1969 until 1971p and in 1971 1 we to Vanderbilt 14 Medical Center, where I was in the Div sion of 15 Clinical Pharmacology and Toxicology til approximat*1 16 1981, when I was recruited to the Univ raity of 17 Arkansas for medical Sciences . 18 00 What is the discipline pharmac logy? 19 A . Pharmacology is one of the ban c sciences 20 of m*dicina# and pharmacology i: :Ostu y of the 21 affect* of drugst the aesign an VolVavipmout of drugs 22 and the touting of drugs for their off cacy in the 23 treatment of diseases . 24 0 . Is your Ph,D . both in pharmaco ogy and 25 toxicology? 8698 1A 2 3 Aa 4 0. 5 A, Yese it is . Are you a registered pharmacist? Yes# I am . Have you taught pharmacology b fore? Yes . I have taught pharmacolo y for the past 6 decade at Tulane medical School as wel as Vanderbilt . 7 00 If one is a pharmacologist, do s one need to 8 know how the body metabolizes various rugs? 9 A* Yes . It*s essential that one oes that? 10 because the length of action and the a feCt.2 that 11 drugs have on the body are generally d pendent upon 12 their metabolism, 13 Q* T4 k4 What is a teratologist? A teratologist is one who stud as the 15 production of birth defects or studies of the causes 16 of birth defects . 17 What experience do you have in the field 18 of teratology? 19 A . Well, the thesis that. I prepar d for my 20 doctoral degree was in the area of ter tology,, and 21 I described the geratogenics of the an iconvulsant 22 Diphanylhydantoin, and generally described 23 the effects that this drug had on the eveloping 24 embryo and fetus . Since that time, I ave been 25 funded for approximately the past twel a years by the 3699 1 National Instutite of Health to look at the effects of 2 chemicals and environment pollutants on perinatal 3 development, which is the development that occurs 4 before birth and shortly thereafter, 5 0. Just as a ballpark figure, how many funds 6 have you received from the National Institute of 7 Health? 8 A* A dollar amount? 9 0. No# numbers . 10 A, Numbers of grants? 11 00 12 A, Yes . I would estimate somewhere aro nd a dozen . 13 QO What in the National Institute of Health? 14 A, The National Institute of Heat h -- the 15 National Institutes of Health -- there is more than 16 one Institute of Uealth -- are those i stitutes which 17 are part of the United States Public H-alth Service 18 whose mission it is to describe and to research 19 various diseases and causes of disease and to report 20 on those causes and develop cures for those diseases 21 and treatments* 22 00 Are you also an editor of a pa or or magazine 23 that deals with teratology? 24 A . Yes . we call it a journal rat or than a magazL .-I 25 butp y*sp I an, 0700 1 0. 2 A, How often does it come out? I believe it is published about every two 3 to three months . 4 And what is the name of that j u--nal7 5 A. The name of the journal is Ter togenesin, 6 Mutagenesis and Carcinogenesis . 7 0. How long havG you been editor f that journal? 8 A. I am not the specific editor, ut I am on the 9 editorial board -- for about the past hree or four 10 years, 11 12 A . Is that a fairly widely distributed journal? YOXF it is . 13 0 . Are you a writer? 74 A, Yeev I am . 15 00 Tell me what you produce as fa as writing 16 in concerned? 17 A . Welle I have written approxima ely 85 to 18 a hundred papers, chapters in books, d ing the past 19 ton or twelve years* They have been a I in the field 20 of toxicology and pharmacology and- son of those 21 have been specifically in the subspeci Ity of 22 teratology, That would be what I have done in the 23 past ton or twelve years . 24 09 You recently put into evidence your CV . It*s 25 an Exhibit, I think it in Exhibit 352 Are some 8701 1 0 a your publications contained in that articular 2 exhibit? 3 A. Year they are . 4 Q. I see a total of 69 . Would tha be approximately 5 correct? 6 A, Well, those may have been the o an I put in 7 some two years ago, However, it has ch nged since 8 then . 9 00 10 A* You have added to that number? Thatts correct . 11 Are you an advisor of any deqr e to anybody I 12 regarding toxicology, pharmacology and or toratology? 13 ke Year I am, 14 Q6 Tell me what type of advising ou do? 15 As I have boon an adviser to the ational Institutes 16 of Health for approximately the last o ght years* nine 17 years, and most recently I have been a pointed by 18 the Assistant Surgeon General to advis the National 19 Institute of occupational Safety and H alth on matters 20 of workers'safotyr and specifically we meet about 21 four times a yearp and when we meett w review grants, 22 proposalst contracts that have been au mitted to the 23 National Institute of Occupational Saf ty and Health 24 for the study of the cancer-causing of ects or the birth 25 defects or mutagenic effects of chemic le that might 8702 1 be found in the workplace . I have also been an 2 advisor to the National Academy of Scie~ce on a 3 variety of issues, and those would be the main 4 classes . 5 0. Are you engaged in any research either at the 6 University laboratories or at the National Laboratories 7 at the present time? 8 A, Yost I am . 9 0. Briefly describe these research projects# 10 if you will, please . 11 A . I an involved in research and have research 12 programs at both places . The research that is being 13 conducted at the University of Arkansas for Medical 14 Sciences is supported by the National Institutes of 15 Health, and its main objective is to determine the 16 effect of chemicals an the growth anddevelopment of 17 the fetus, and it is also to determine the mechanisms 18 whereby chemicals cause liver disease and diseases 19 of other organs . The research that is being conducted 20 at the National Center of Toxicological Research 21 is focused again on those two areasp looking at the 22 mechanisms whereby chemicals produce liver diseaxop 23 alter liver function# and also the mec anism by which 24 certain chemicals are able to affect r production . 25 Q* Have you written on the effect of chemicals 8703 on the liver? 2 A, Yast I have, 3 go Row many papers have you publis ied with regard 4 to that particular area of toxicology? 5 A, I would have to estimate it . I think it is 6 around ton to twelve, maybe even more* 7 go 8 A. Are these projects ongoing? Year they are . 9 go 10 A* Do they involve animal studies? Year they do, nd 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 2-1 1U 8704 Are you a hands-on person when it c~:,mss to 2 auimal studies? 3A Ya3, I participata daily in the animal 4 experiments at both laboratories . 5Q What is risk assessment? 6A Risk assassmant, is the proceduze of making a 7 projection or forecasting the likelih od or the 8 probability that some adverse affect ay occur as a 9 result of exposure to some substance . 10 Q Is that a tool of trade to the toxicologist? 11 A Yea# it is . 12 Q Is the pharmacologist involved in that particular 13 tool as well? 14 A The pharmacologists have an im ortant part 15 in that because the basic underlying rinciples of ris' 16 asses3ment must rely upon certain asp cts of the 17 absorption, metabolism, the excretion of chemicals, 18 so that conceptually, yes, risk asses mant relios on 19 pharmacology . 20 Have you done any risk assessm at? 21 A Yost I have . 22 Q For WLOM? 23 A I have conducted risk assess ts for the 24 United States Environmental Protect:: Agencyp the United States Department of Justice, nd for industry . 25 2-2 8705 Q Are you teaching any group or 0 ganization 2 regarding risk assessments at the pros at time? 3 Yes, I am . 40 What organization would that b 5A I have a contract through the ited States 6 Anvironmental Protection Agency to pri3 ide basic 7 risk assessment teaching to the eight southeastern 8 states and also to the U .S . EPA in Rai ion IV, which 9 is in Atlanta, and what we are doing a providing 10 a basic introductory course to state gencies, 11 the Department of Health,, the Water 01 ality Divisions, 12 the Department of Pollution Control aj d Ecology . 13 we have already conducted one such co, rse here in 14 Tennessee and it is designed to provi- a a foundation 15 for these people and to introduce the to the 16 principles and concepts of risk asses meat so that ths~ 17 are better able to make public health decisions when 18 water supplies or air supplies or gro, nd are 19 contaminated with chemicals . 20 0 Where are you going from here, Sir? 21 A I am going to Atlanta, Georgia 22 Q Por what purpose? 23 A We are going to present the cc arse to the EPA 24 and to the State Department of Health for the State of Georgia . 25 8706 Q Do you -- have you put together a textbook 2 for risk assessment? 3 A Yes, I have . 4 Q Is that a textbook that will b used by members 5 of the EPA in these upcoming classes? 6 A Yes, it will . 7 What is the -- what is a mutag a? 8 A A mutagen is a substance that a able to 9 interact with the genetic material of a call and causoi 10 a change in that genetic material to enerally I I influence the future development of at Coll . The 12 cell can be one which is in the body r the call 13 could be &n, egg or a spormatozoa . 14 Have you published regarding a tagenicity of 15 compounds and the like? 16 A Yost I have . 17 How many Publications? 18 A Again I would have to estimate maybe a half 19 a doxon . 20 Q Nowt that journal to Vhich you referred is 21 the journal of what? 22 A Toratog*nosis, Mutagonesis and Carcinog*U*2i3 . 23 Q Have you published in the are of carcinogenesis? 24 A I have published in the area garding tumor 25 growth and the treatment of certain pas of tumors, 2-4 8707 1 solid tumors as well as leukemia . The answer would 2 be yes . 3a Have you done risk assessments as far as 4 carcinogens are concerned? 5A 6Q Yes, I have . We've discussed pharmacology . We've discussed 7 teratology . You are a toxicologist but I don't 8 think we have really given a true def .Lnition as to 9 what a toxicologist in . Would you g :Lve me one* 10 ploaxe? 11 A I will try . A toxicologist i one who studies 12 the adverse effects of chemicals and ther substances 13 on the living systems . 14 a Historically when did this sci~ nce come into 15 fruition? 16 A The origin of the science of ti xicology 17 is in the discipline of pathology, al bough within the 18 modern medical community within the U, ited States 19 toxicology has really evolved out of he basic 20 discipline of pharmacology, and all o, the original toxicology training programs were esw ntially part of 21 the departments of pharmacology . 22 23 Q When was the first professiona society of toxicology established? 24 A 25 The first professional society was established 7 %,.,1 C. t~ I aLel- I "A ^W -8 ILI - - - - 8708 2-5 Q A fairly new discipline as it ates to the 2 society itself? 3 A That is correct . 4 Q aave the principles and concep 3 of toxicology 5 changed substantially or none at all :ver the last 6 ton years? 7A The principles and concepts ha changed . 8 They have evolved over the past ton y s and most 9 recently there have been significant as in those 10 principles and concepts . Q Can you tell me what they are? 12 A Well# specifically in the area of cancer 73 causation . In the past the design c experimental 14 to studies/determine whether or not chea cals cause 15 cancer was simply a mission to use th~ highest 16 tolerated dose that would produce tum, rs in animals 17 to simply determine whether it would , r would not 18 produce tumors . It has become gen& al knowledge 19 that the mschanism, by which chemicals produce tumors 20 is critically important in making saf ty assessments 21 and trying to develop public policy, nd it has been 22 determined that certain classes of co: pounds produce 23 cancer only when they produce damage o the tissue 24 and they produce it recurrently throu hout the lif0t F 25 and so that there has been the evolut on of new 2-6 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 8709 concepts regarding cancer causation and the factors that are important in that causation . Q Sir? What professional societies do you belong top A I belong to the Society of Toxicology# to the Teratology Society, to the American Association for the Advancement of Science, to the American Society for Pharmacology and Experime tal Therapouticsi a What is an experimental th*rap utic? A Experimental therapeutics is t a design, development and testing of new drugs for their efficacy or their ability to cure diseases . Any other? National Academy of Sciencer dic u name that? No . I am not a member of the National Academy of Science . I have served as an advisor, but I am not a member of the National Academy . Now about the Now York Academy of Sciences? A Year I am a member of the Now York Academy of sciences . Q Have you received any awards in the area of toxicology since you have been in the discipline? A Y*Sj I have . Q What was that? A In 1978 1 received the achievmqnt award from the 2-7 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 8710 Society of Toxicology, which is that a ard given to a scientist under the ago of thirty-si who last made a significant contribution to the scie it's given to only one person annually and t's not actuall given annually, but some years there t ve been no awards given . While you were in the state of Tennessee did yoi~ belong*to any state boards that dealt with medicine or toxicology or pharmacology or the ike? A X didn't bolong to any b ards, bu.t I did have the occasion to he an adv :zt:trotolthe Medical ZX&Ainor's Board of the State of T Osseo . 0 In what capacity? A I served the attorney's -- the Attorney Gen*ral'.9 office in advising the Medical Examin r's Board on the usual course of medical practice as i relates to the use of drugs, the pharmacological asp cts of it, in reviewing licensure of in reviewin the revoking of licenses of practitioners in the S ate of T*nnessets,~ 0 Do you have at the School of P armacology in Little Rock a procedure whereby medic 1 doctors can call you and determine the toxicity o various compounds and chemicals? Yes, we do . Tell me about that, sir, and me how it's 8711 1 used . 2A Wall, we have a service which i s used by the 3 practitioners at the University Hospit al in which 4 we are available to them 24 hours a d y, 7 days a weak 5 to provide consultation regarding the effects that 6 might be expected or the diagnosis of chemical 7 injury, and that service is also provi ded to the 8 U .S . EPA contractors on a national ba is, so that 9 we essentially are available to all t n regions of 10 the U .S . EPA throughout the United St tes . 11 MR . GENTRY : Your Honor, at this point 12 of time I would represent to t a Court, 13 although the Court0s memory is better than 14 mine, that Dr . Harbison has pr viously 15 been accepted by the Court as toxicologist, 16 an expert in toxicology . we ould also preseni 17 him to the Court now as an exp rt also in 18 pharmacoloqyo teratology, and isk assessment 19 an it relates to chemicals and drugs . 20 THE COURTs Is there any objection? 21 MR . GILREATH : No, Your Honor . 22 THE COURTt All right, a r . 23 BY MR . GENTRY : 24 Q Dr . Harbison, let's go back to the research 25 which you described for the Court Jun a few minutes 2-9 8712 ago as relates to the liver . Can give me a 2 mundane description of what your p a have been 3 doing as it relates to the various grams you have 4 been carrying out? 5 A Wellp we have been trying to rmine the ways 6 in which chemicals affect the liver specifically 7 we have been interested in narcotics analgesics# 8 that is compounds that are able to af act pain, 9 and we have been interested In the ef :O'cts that these 10 analgesics have on some of the enzyme that are I I produced in the liver, specifically a SGPT and SGOT . 12 0 Let me stop you right there . We've had a lot 13 of discussion about liver function toa ts and I notice 14 you refer to enzymes . Tell me the ifferenc*j 15 if you will, please . 16 A Wellf SGPT, serum glutamic pyr vic transaminase 17 and the SGOT, which is a similar anz a, are enzymes 18 that are produced or synthesized in t a liver . They 19 axe normally released from the liver ad various 20 changes in the liver can alter the laiel of these 21 enzymes that you would find in blood . And SGPT and 22 an SGOT is not a liver function test . It is an 23 enzyme or it is a set of enzymes tha are found in 24 the plasma or in the blood which are by the 25 liver and they can be altered or cha god or elevated 2-10 3713 1 depending on hov the liver is acting at a particular 2 moment in time . 3Q Is this an animal study t.lat you have been 4 carrying on or a number of animal studies? 5A We ar* carrying on animal studies and we have 6 also conducted human studies . 7 As it relatsm to the liver enzlmes? 8A That is correct . 9 Tell me what you have done, if you will, 10 please . I think this is pretty impoxtant . A 11 What we have done so far is we have found that 12 drugs like analgesics, including the over-the-counter analgesic acetaminophen or Tylenol, axe able to chang4i 13 14 those enzymes within the blood and car increase the 1*vels of those enzymes within thi blood# 15 so that the administration of certain analgavics can 16 cause a significant elevation in SGPT or SGOT levels . 17 Is that long lasting? 18 A 19 It is not long lasting . It will generally be a trenchant effect . We have also found that other 20 drug substances which are able to alter the metabolism 21 of the liver, such things as the soda ive hypnotics lik a 22 phonabarbital, the anticonvulsants li a 23 dipheallhydantoin, are also able to i crease these 24 enzymes in the blood because they havi a nonspecific 25 8714 1 effect of increasing the synthesis of enzymes througho 2 the liver and as a result of that effe, :t cause an 3 outpouring of these into the bloodstre, Im . 4a Is the increase of enzymes into the bloodstream 5 by the introduction of these analgesic & into the bodyp 6 is that indicative of liver damage? 7A No, it is not . 8Q What is it indicative of? 9A Wellf it is indicative of a cha age within 10 the liver whereby these compounds and 3thers can 11 cause an increase in the synthesis of these enzymes 12 and thereby the increase in the produc tion or the 13 synthesis of the enzymes causes an inc rease of these 14 in the bloodstream# so it's a simple p aysiological is response . 16 17 18 19 20 21 22 23 24 25 8 715 In these experiments or tests, what have you- 2 do you have reason to look at liver sli les? 3 A* Yesp I do . 4 00 5 As How often? Ohp certainly on a weekly basis # probably 6 every couple of days . 7 And for what purpose? 8 A, For the purpose of determining whether or not 9 there is a cell death that has occurred or what other 10 changes might have occurred within the liver, which 11 might have led to the elevation in the enzymes or the 12 other effects that we may have seen . 13 Now# you used a word .that has uzzled me thcouqb14 out this litigation . We are talking bout the liver 15 nowp and you refer to call death . is t possible 16 to have damage to the liver without hav ing call 17 death? 18 A* 19 00 Yes* it is . Lot me ask you if you have, say * ton or eleven 20 drinks one evening* would that create l iver damage? 21 A. Yes# it would . 22 00 Under ordinary circumstances wi th an ordinary 23 human being# would it create cell deatt ? 24 Ae No, it would not likely create call death or 25 cause cell death, 8716 0 . Explain to me the difference b4 2 and cell daathp if you can? damage 3 A, well# in damage there is a chai in the 4 cells of the liver, for example, in wh: these cells 5 may become leaky, that is, they cause j discharge or 6 a leaking of the enzymes into the bloog trean . The 7 cell death is where the call in actual .' destroyed,, and! 8 it needs to be replaced, and the cells the liver I 9 are quite easily replaced . So that in came of 10 call death, there will not be any sort survival 11 or any rebounding of that particular ci 0 Itis dead, 12 0 . is the liver a sensitive organ or resilient 13 organ? 14 A, 13 The liver in a resilient organ What is its purpose and functi n? 16 A, The purpose of the liver is to clean the blood 17 of substances that are normally produc d by the bodyl 18 such as steroids, the breakdown produc a of bloodl 19 for example# bilirubin . It also has a function to 20 synthesize or to produce other substan an like clotting 21 factors# steroids and other materials hat it produces 22 or altars by metabolizing them . So it has two 23 functions# really* One is to cleanse I he blood,, 24 to serve as an excretory organ# and the other is 25 to synthesize materials that are essential for life . 8717 .3-3 1 Q . 2 A. What is necrosis? Necrosis is colldeath which can be seen an 3 observation of the liver . 4 0. In your experiments# to which y u have been 5 referring# do you sometimes see necrosi on your 6 liver slides? 7A Yes, we do . 8 0. The liver damage, which you just described 9 earlier, not the call death* but the 1 vex damage, 10 can you see it on your slides? 11 Ao oftentimes you will not be abl to see liver 12 damage . 13 00 It depends on the range of the damage? 14 A . That in correct . 75 0 . Are you familiar with the compounds carbon 16 tetrachloride and chloroform? 17 A . Yost I an . 78 00 19 AO And in what manner? Wellp I have generally known a out than for 20 the past decade or more . While I was n pharmacy 21 school# I had the occasion to prepare ompounds that 22 contained chloroform and dosages of so ication for 23 worms containing carbon tetrachloride, I have 24 ganerally throughout my education exp ience been expo 25 to basic research that has been condu: ad on carbon 9718 1-4 1 tetrachloride and chloroform . I have one basic 2 research on carbon tetrachloride and c loroform and 3 have an active research program at thi point on 4 carbon tetrachloride and chloroform . 5 well# I would like to explore hat, but first* 6 lot me ask you thist Have carbon tetrachloride and 7 chloroform been used as analgesics in the past? 8 Q* AS analgesics? 9 Q. A, Yes . Actually, yesp they have . Carb n tatrachloridel specifically -- carbon tetrachloride he been used 12 an a topical treatment for burn injurio approximately 13 twenty years ago . 14 Q . Have they been used as drugs in the past? 15 A, Yost they have . 16 Q6 In what manner? 17 A, Well* carbon tetrachloride has eon used 18 quite extensively in the treatment of w rms . Carbon 19 tetrachloride in the southeastern part f the United 20 States was extensively usodp and actual y was in the 21 textbooks of pharmacology when I was ta inq pharmacology 22 There are reports of the successful tre tment of more th 23 a hundred and twenty thousand patients ith carbon 24 tetrachloride . Chloroform has also be* used as a 25 drug, It has been used as an anesthati It has also 8719 1 been used as a preservative# and it has been used as 2 a carminative or a flavoring agent in t a solution 3 of other drugs and substances which don't taste 4 very good . 5 0. Before we got to your research rogran on 6 carbon totrachloridep tell me about tha study with 7 200000 people . What type of study was it? 8 A, The study of 20,000 people was a study in 9 which the outcome of the treatment of atients who 10 had tapeworms was conductodi that is t a patients 11 were followod, .aad it was an observati n of the advsrze~ 12 offsets that occurred as a result of t o use of carbon 13 tetrachloride or the lack of those off eta . 14 What type of domes wore given a those people? 15 A* The general recommended does w a approximately 16 five grams for an adult, given an a si gle dose# 17 followed in approximately two weeks by another done 18 If the worms wore not passed within th t period of 19 time . 20 00 21 A* What dose would that be# the a cond dose? The second dose would have bee the same# 22 approximately five grams for an adult *rsono 23 QO Ton grams in two weeks? 24 A* That's correct* 25 00 Tell me about your research pr gram as it relat 872 -4 1 to carbon tetrachloride? 2 A, The research program that we ar conducting 3 in one to describe the inter-action bet eon carbon 4 tetrachloride and chloroform in other c emicals, 5 and we have defined the ability of carb n tetrachloride 6 and chloroform to produce liver damage, and the ability 7 of other chemicals to increasethat ability to produce 8 damage# and our general objective is to describe 9 the synergistic activities, if you will, between 10 carbon totrachlorideg chloroform and other chemicals, 11 go Let me refer you to Exhibit 18, Are you 12 familiar with that exhibit? 13 A* Yes$ I am, 14 As a result of the experiments that you have 15 been doing with carbon tetrachloride a d chloroform# 16 can you tell as and the court what the synergistic 17 effects of all those chemicals there w uld be with 18 carbon tetrachloride and chloroform? 19 A* I don*t believe there would be any synergistic 20 effects between those compounds listed on there with 21 carbon tetrachloride and chloroform . ur researchp 22 as well as that of others, has really *scribed 23 twachemical classes that caused synerg stic effects 24 between carbon tetrachloride and chlor form# and those 25 two chemical classes are alcohol or va ious alcohols, 8721 7 1 and ketonesy and those are really the o ly two classes 2 that have been described which cause a iynorgistic 3 effect between carbon tetrachloride and chloroforme 4 THE COURTs Ask him to des ribe what 5 he means by synergistic effect . 6 MR . GENTRYs Certainly# Ya r Honor . 7 8 A, Would you describe what you mea by that? Yes, Synergism is the effect w areby when 9 two chemicals are given or one is expos d to two 10 chomicalap there is more than an additi a effect . You 11 don't simply add up the effects of one ersus the 12 other, but when the two are administers together, 13 there is a greater than an additive of act, 74 THE COURTs The witnesses here have 15 used the word potentiation* W uld that be 16 pretty much in the same class f what you 17 are talking about -- maybe pro ucinq a more 18 powerful effect possibly? 19 THE WITNESSt It's not a ore powerful 20 effect . The term potentiation has very 21 specific meaning, Potentiatio is a term 22 that is used when you give one compound that 23 has no effect 22612 . It has n intrinsic 24 or inherent toxicological prop rties, But it 25 greatly exaggerates the toxici y seen by anothe 8722 compound . So rather than seaing tAs 2 effect that you would expect at this particular 3 dose levell if you give the two together 4 now# you would see considerably more than 5 you would have expected . 6 THE COURTs So there in a Ufferencis 7 between the two concepts? 8 THE WITNESSs Yen,, air, thare in . 9 Q. (By Mr . Gentry) Well# let's ta k about potentii- 10 tion as it relates to these compounds o Exhibit 16 . 11 Can you give me an opinion if t ere is a 12 potentiation between carbon tatrachlori a and/or 13 chloroform and the other compounds? 14 A, The same would applyr that the otentiation 15 and the synergism that occurs is confin d to two 16 distinct chemical classese and those ar alcohols 17 and those are ketones . There aran1t an alcohols 18 or ketones on that list . 19 0 . What in a metabolite? 20 A, A metabolite in alroduct that a produced from 21 a chemical or a drug that would be ing sted in man or 22 that would be given to an animal . It a a changed 23 material . 24 00 Are metabolite* important in y ur research 25 as it relates to carbon tetrachloride nd chloroform? 8723 1 9 2 3 4 5 6 7 a 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 A, Yes$ sirg they are critically I portant . Q . Tell me why? A . Because carbon tetrachloride an chloroform themselves do not produce liver injury . It Is only the metabolites of carbon tetrachloride and chloroform that produce the injury* The carbon te trachloride and chloroform themselves are rather a able molecules, and until you extract a chlorine from he molecule it does not become biologically import nt or reactive within the liver system or within othe organs of the body . Q . Axe there some chemicals# can undsp or drugs that will produce more metabolites tha others? A. That will result in the produa ion of more metabolites for themselves? Yes, A, Yes# there are, Where do you classify carbon t trachloride and chloroform? A, Their metabolism is fairly six Is# and they do not produce a lot of metabolites, Is that Important to your stud ? Yes# it In* Tell as why? A* Wellp because in trying to dot rmins the 8724 -10 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 mechanism by which a drug or chemical ,oauces an affect, it in important to know what metabolites are* because in most all instances in w there is liver damage, the liver damage is produ d by a metabolite . It is not produced by a pa nt compounded cell . in the case of carbon tetrachlor a and chlorof there are really very few metabolites ducedy so it is a much easier task to identify what causative agent is than, for example# in one in you might have fifty metabolites or considerably 0 09 Have you reached any conclusio s as a result of your studies of carbon tatrachlorid and chloroform in the laboratories? A . Yea . Synergistically and the like? Ae yen, 0 . What are the conclusions? A. Well* the conclusions are that in order to increase the toxicity of carbon tatrac loride and chloroform as seen in the livere that 9 to be able to produce the necrosis or cell death# it in essential that the compounds be given for a peri d of time which will allow synthesis of new enzymes to increase the ability of the liver to be able to con art the carbon tetrachloride and chloroform to the mo a toxic species V $725 3-11 2 and the more proximate cause of the inj ury, Can you say that in a little si mpler terms7 3 A, Wallo it's essential that the c ompound changed 4 the metabolism of the liver in order tc create a 5 liver which is now different such that it handles 6 carbon tetrachloride and chloroform in a different 7 manner than it did before . 8 00 Now, in that change damage or call death? 9 A, The change that we see with the carbon 10 tetrachloride and chloroform? I1 0. ~ Yen . 12 A* We are looking at both damage a s well as 13 call death, 14 Q* Is there - excuse no . Rave you finished? 15 As We look at both, 16 Zs there a threshold of the amount of carbon 17 tetrachloride and chloroform that you g ive the 18 animal over which there is cell death and under which 19 there is damage? 20 A* T&SO 21 00 You have read a number of parti of the 22 transcript of this trialp have you not? 23 A* Yesp I haves 24 0 . And you have attended certain (Lays of this 25 trial as well# have you not? 8726 1 A* Yes# I have . 2 0. Are you familiar with Dr-Rodric s and his 3 testimony? 4 A* Yes* I am familiar with his too imony# year 5 am. 6 00 Are you familiar with his calcu ations? 7 A* Your I am, 8 0. Are you familiar with the word r words that 9 he used on Exhibit 237 --*cumulative ex osuze .' 10 A, Yesr I am . 11 QO What did.he mean by thatg Doctor? 12 A, Well* by cumulative exposure he added up the 13 levels that the individuals would have been exposed 14 to over a period of time and took that cumulative 15 amount to be the amount that the individual would 16 have been exposed to and thereby would have had in his 17 system to produce the effects which he says would 18 occur* 19 Or Was Dr, Rodricks a pharmacolog at? 20 A, I don9t believe so* I think h testified 21 that he was a chemist or a biochemist . 22 06 As a pharmacologist, and we ar talking fc 23 specifically about carbon totrachlorid and chloroformp 24 an a pharmacologist# does the cumulati a exposuze 25 make sense as far an human bo*nqx are oncerned? 8727 and A, No, air, it does not . 2 00 What happens to carbon tetrachloride and 3 chloroform -- and/or chloroform when the human 4 body either ingests it or inhales it? 5 A, Carbon tetrachloride and chloroform are 6 readily excreted . Carbon tetrachloride and chloroform 7 are blown off in the expired air . They are also 8 rapidly converted to metabolites and rapidly excreted 9 following that conversion . So they do not stay 10 around for a long period of time, 11 00 When you say rapidly excratedp are you talking 12 in terms of hours, daysor months? 13 Ae I an talkinq in periods generally of days, 14 it certainly would not be months, but it probably 15 would be days, 16 17 18 19 20 21 22 23 24 25 8728 1 a When you ingest carbon tatrach ids and/or 2 "loroform where does it go? 3 A when you ingest it most of it ill go immediate' -Y 4 to the liver, The vessels in the in estins, which 5 are called the greater omental vessel 0 are those 6 which collect the material from the i testine and will 7 generally go directly to the liver, a d chloroform a and carbon tetrachloride are compound which generally 9 on the first pass through the liver w 11 be 10 sequestered by the liver, so they are very efficiently 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 4-2 8729 1 taken up by the liver, so very little iould get out 2 into the rest of the system in circula ion following 3 the oral ingestion of those materials . 4 Q When you inhale carbon tatrachl ride and chloro 5 what happens to them? 6 A When you inhale carbon tetrachl ride and 7 chloroform it would be likely that they would get 8 into the systemic circulation much more efficiently, 9 that in to the brain and to other org na of the body, 10 before they got to the liver, because the blood 11 would go to other organs first . 12 In light of the characteristic of carbon 13 tetrachloride as those characteristic relate to the 14 metabolizing by the body of the compo ndst is daily 15 dosage more important .than cumulative exposure? 16 A Yes, it is . 17 0 At the risk of being repetitio a, explain to 18 me again why . 19 A Walle the daily dosage is impo tant because 20 that is the dosage which will determ.ne whether or 21 not the level of chemical reaches a evel that in 22 able to produce some response in the body, and unless 23 it's able to reach that level on a daily basis it 24 will not produce any effect . 25 I'm going to slip sideways on the direction 4-311 1 2 3 4 5 6 7 8 9 10 11 12 13 14 is 16 17 18 19 20 21 22 23 24 25 3730 1 of this examination if you will allow me, sir# and ask you if there's a book called Clinical Toxicology of Commercial Products? A Yes, there is . 0 What's the purpose of that book7 A The purpose of that book is to identify the constituents that are contained withir commercial products for the purpose of treatment and diagnosis of persons who might have unintentionally or intentionally ingested those products . You will findl: that text in most poison control centers and in most emergency roomer because it is a quick reference to allow one to determine the makeup of some material that someone may have ingested . Q Is it substantial in size? A Yes, air ; it's probably four tc five inches thick . It's quite a large textbook . Q At my request did you extract from that book some information on carbon tetrachloride as it relates to commercial products7 A Yes# I did . 0 1 know it's rather lengthy, but tall us about some of the products, some of th co arcial products in which we find carbon tatrachl :rid presently and then give us an estimation of how man products there 4-4 1 2 3 4 5 6 7 a 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 0731 are with a not unsubstantial amount of carbon tetrachloride contained therein . A Wall, carbon tetrachloride is contained in probably, I would estimate from the li t . maybe thirty to fifty products . It is contained i paint removers it's contained in a variety of carbure or cleanersp it is most extensively used as a pasti ids and as a fumigant, and a What's a fumigant? A A fumigant is a material that is used as a pesticide, but because it is volatile ou are able to put the material within an enclosed space and have it got to essentially all parts of that space because of its volatility and thereby kill off the post that you don't want in there . Do you use that with grains? A With grains? Q Yes . A Yes, air . 0 1 notice one of the first bran( names is Acritat 34-66 fumigant . A Yes . 0 By whom is that made? A It's made by Stauffer Chemical Company . There's also a reference to re rig*rants . In 4-5 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 8732 carbon tetrachloride contained in refrigerants? A Year it has also been used as refrigerant . Q How many different companies, pproximately, how many different manufacturers# use carbon tetrachloride presently in the manufac ture of their var ious products? A Well, I've not closely counted them . I would say there are probably at least a doz n . In that book to which we have reviously ref erred, Clinical Toxicology of Comm rcial Productse is there a section under carbon tetrac hloride dealing with minimum acute toxicity concentrat ions? A Yes . Q What does that mean? A I'm sorry, lot me make sure I nderstand . Did you say is it in the book or is i in this paper? 0 Is it in that? A On this paper? I Q Yes . A Year it's on the paper . a Is that not contained in the bo0k? A No, it is not contained in the book . 0 Where do you got the minimum ac ute toxicity concentrations? The minimum acute toxicity con entrations are 4-6 8733 1 those concentrations which are derived from a set 2 of publications that the United States Environmental 3 Protection Agency published some years ago and they 4 Multimedia are called Environmental G alst and what 5 It allows one to do is to calculate a concentration 6 to which one could be exposad for sho t periods of 7 time, and that's what the minimum acu a toxicity a concentration is . 9 What is the minimum acute toxi ity concentration 10 for carbon tetrachloride In air? 11 A it's ton parts per million . 12 Q 13 k In water? It's nine hundred seventy-five parts per 14 million . 15 Q 16 A Parts per what? Per million . 17 Nowp I see something, land . ould that be 18 in the dirt or earth or what have you 19 A That would be soil contaminate or containing 20 carbon tetrachloride . 21 0 And how many -- what's the zi inum acute 22 toxicity concentration for that? 23 A That's one thousand nine hund ed parts per 24 million . 25 Q Where is that information con ained that you 4-7 8734 just gave me as far as the EPA 4.9 con rned? \ 2A It is derived from t~he multime a Lnvironmental 3 Goals, which is a methodology that th EPA proposed 4 for determining concentrations to whi people 5 could be exposed for short periods of ime as well 6 as long periods of time . 7a Has the EPA derived a mathomat cal formula 8 which translates into permissible con entrations of 9 carbon tetrachloride over a 24-hour a day 7-day a week 10 environmental circumstance? 11 A Yost it has . 12 a Can you tell me what that is f ir air? 13 A The estimated permissible conc !ntration for airs 14 and that is the concentration to whic one can be 15 exposed for 24 hours a day 7 days a w iek, is point 16 zero two parts per million . 17 0 That would be twenty parts per billion? 18 A That's correct . 19 a All right . What about water? A 20 For water it's two point three one parts per million . 21 22 a And that's 24 hours a day 7 da a week? A 23 That is correct . 0 24 For a lifetime? 25 That is correct . 3735 1 Q 2A And that was parts per million part3 per million . 3a All right . Land? 4A Land is four point six two par s par million . I 59 Doctor, are carbon tatrachlori a and chloroform 6 suspected carcinogens? 7A Yost they are . Tell me how and why they are a spocted as 9 carcinogens . 10 a Both carbon tetrachloride and hloroform 11 are suspected carcinogens because in ome animal 12 studies it has been found that both o these agents 13 are able to produce tumors, and spoci ically tumors 14 of the liver . 15 0 Under what circumstances? 16 . A Under circumstances of high cc cantrations 17 over a prolonged period of time and u der circumstances 78 in which there is necrosis, call doat I that occurs 19 over a substantial period of the life ins of the 20 organisap the animal . 21 22 A Is chloroform a toratogen7 Chloroform is teratogenic in ice or it has boom 23 found to be teratogenic in mice . I in not a 24 human toratogen . 25 Is carbon tetrachloride a tar togen? 8736 e- 1 A Carbon tetrachloride is -- therB is considerabl 2 less evidence ovea for carbon totrachl)ride . it is 3 not a human teratogen . 4 Are chloroform and carbon tetra :hloride 5 mutagens? 6 A Nop they are not . 7 0 Is that important? 8 A Yes, it's extremely important . 9 a Tell me why? 10 A Well* if carbon tetrachloride aid chloroform 11 were mutagenic substancest what that miens is that 12 they have the ability to bind to the ganatic material, 13 the DNA# and it means that they can caise cancer 14 and that exposure over & period of tims resulting 15 in that genotic damage could in fact lead to tumors, 16 but neither carbon tetrachloride or chLoroform 17 have boon found to be mutagenic, which means 18 essentially that they do not bind to t o genetic 19 material and they do not cause cancer y causing a 20 change in the genetic material . 21 Q Were you in the courtroom yesto day when Dr . 22 Sullivan talked in terms of binding? 23 A Yes* I was . 24 0 He described a physical prop rt of these 25 compounds that I think made it diff:cu t for them to 8737 1 bind . Rra you familiar with that? 2A Yost I am . 30 4 91 Tell us about it again, if you ill, please . Welll carbon tetrachloride and chloroform# 5 because they contain only a single ca ban atome 6 cannot forin intermediates which are a le to bind to 7 macromolecules or various molecules within the 8 cell, and more importantly they are n t able to bind 9 to DNA to cause some sort of damage a error within 10 that material, so they do not have th chemical 11 makeup to be able to be biotransfor=e or converted 12 to metai2olites which are able to bind 13 Is this important as it relate to the manner 14 in which people view carbon tatrachlo ide and chlorofai 15 when they are talking in terms *I. car inogenicity? 16 A Yost it's very important . 17 Tell me why . 18 A well# again because neither of those two compounds are able to bind to DUA . hat means 2,09 that they will not be able to initiate the process of 21 cancer or cause the process of cancer or that process 22 which leads to cancer, and unlike oter substances 23 which are it means that these compou ds cannot be thou 24 which bind and cause cancer themselv s . They must 25 have some other event# either throug. the process of 8738 1 killing the calls or using massive dos a to kill calls! 2 that will ultimately lead to the cance proces3 . 3a There are technical names for t a type of 4 toxins theme are an opposed to the type of toxins 5 that might bind with a call# are there not, sir? 6A Yost Sir . 7 We have heard them a number of ti=esp haven't 8 we? 9A Yea, we have . 10 0 Just for the purpose of the re ord let's voice 11 then again and then forget about them# because I think 12 what you have described is adequate f r our purposes* 13 a Okay . Those chemicals which re able to 14 bind to ONA and initiate the process f cancer are 15 called genotaxic chemicals . Those c emicals which 16 are not able to bind to DNA but can u der certain 17 circumstances cause cancer because th y consistently 18 cause call death at high levels or ma sive exposure 19 levelsp those compounds are called epJgenetic 20 carcinogens . 21 a 22 A And what is carbon tetrachloride and chloroform! Carbon tetrachloride and chloroform are 23 opigenstic carcinogens . 24 a Doctor, I'd like for you to, if you have it in 25 front of you, turn to Exhibits 232# 2 30 2340 235 and 8739 1 the supplements put into the record by Dr . Rodricks 2 as a result of summary calculations . Do you 3 recognize those? 4 A Yess I do . 5 First, for the purpose of your testimony, tell 6 us what those calculations are, about -- toward whom 7 they are directed* and whether or not there are any 8 footnotes on any of those . 9A Okay . Exhibit 232 is the estimated chemical 10 dozes of selected chlorinated hydrocarbons to S . Sterling, 11 1969 through 1978, and it is an estimated cumulative 12 dose of carbon tetrachloride, chloroform, chlorobenzens! 13 and tetrachloroothylone, and also an estimated average 14 daily dose of those same materials from drinking water 15 and from inhalation exposure . 16 Q What's 2337 17 A 233 is essentially the same thingr only this 18 is for D . Johnson and it's 1976 through 1978 . 19 9 And 2347 20 A 234 is for the Maness childo and this is April 21 176 through March 178% 22 a Now, the next group of papers you have would be 23 Exhibit 237, and what is the differ :n 0 in those papers 24 and the ones that you have just dos r bed? 25 A The next one I have in 235 . 3740 1 Q All right . Then you have one that's 237, 2 the footnotes . It's not so marked . 3A It's not so marked 237, yes, but it has the 4 footnotes which are the -- 5 MR . GZNTRYs I'm Berry, Your Honor, 6 I'm transposing numbers, which I'm wont to 7 do . It's 327 . 8 THE COURTi All right . 9 BY MR . GENTRY : 10 Q Those are the ones with the fo tnotes that 11 are.essentially the same as the provi us exhibits (11 12 except they itave footnotest is that c rroct, sir? 13 A That is correct . 14 Q Did you have reason to review those recently? 15 A Yost I have . 16 Q For what purpose? 17 A For deriving the assumptions that Dr . Rodricks 18 used in the calculations of his estimated doses . 19 0 Turning to 327, which is the or* with the 20 footnotest lot's look at the daily dosage of carbon 21 tetrachloride and chloroform for Mr . Steve Sterling, 22 both as a result of inhalation and in5astion, 23 Do you see that# air? 24 A Yost I do* 25 What is the daily dose for chl rofo rm shown in 8741 Dr . Rodricks' figure? 2 A The daily dose for chloroform m ould be point 3 zero two two milligrams per kilogram . 4 Which extrapolates out to what& parts per 5 bill ion? 6 A Wellp it would bo parts per bil lion, but that 7 would not be the proper way of using arts per billions, 8 Q Because of the milligram per k logram? 9 A That's correct . 10 Is there any as far as inqeati n is concerned 11 for chloroform? 12 A You mean inhalation? 13 Q 14 A I moan Inhalation . No, there is nothing for inhal tion . 15 wowo what in the average daily dome for ingestionj 16 Steve Sterling, shown by Dr . Rodricks in Exhibit 327 17 of Carbon tetrachloride? 18 A For carbon tetrachloride it is point two three 19 milligrams par kilogram . 20 Q 21 A And inhalation? inhalation is point eleven milligrams per kilogr 22 0 Now, there's an interesting footnote with 23 regard to the exposures here . Read those footnotes, 24 if you will, please . 25 A The first footnote, number 1, s body weight 3742 1 assumed to be sixty kilograms . Foot .iota number 2 2 is calculations are based on drinking dater consumpti. 3 through November 1977 and inhalation a gposure through 4 March 1978 . Footnote number 3 is ass =ed two liters 5 per day of well water consumed . Ave rage ex -- I'm 6 sorry . Number 4P the footnote number 4t is average 7 exposure for highest year in milligram per kilogram 8 per day . 9 All right . Now, just a 9:cond The average 10 daily exposure to which you have ust eferred is the 11 highest year? 12 A That's what it Says . 13 a That figure does not take into consideration 14 any othez years that were lower than the highest 15 year? 16 A Not it does not . 17 Is that footnote the same for Daniel Johnson 18 and for Jimmy Maness? 19 A Year it is . The only difference in that 20 on Maness it's footnote number 3 rather than footnote 21 number 4, but it's essentially the same wording . 22 a Still referring to 327p what did Dr . Rodricks 23 assume in that table as it relates to these daily 24 doses? 25 A H* assumed that there would be a consumption 9743 e~ 1 of two liters of water a day and he asIsumed some 2 other things about the amount of tine spent within 3 the bathroom in showering* and so forl:h, for the 4 inhalation exposure . 5Q Did he also accumulate those di ily dozes over 6 a full year? 7 A Yes ; he did . He accumulated ham for a full 8 year period of time and then he added the two of them 9 together ., that is the ingestion and is halation . 10 0 As a pharmacologist do you pari eive to be i 1 proper and correct? 12 A Not sir, that is not correct* That is 13 incorrect . It ignores all of the baj ic underlying 14 principles and concepts of pharmacoloi ,y and 15 toxicology . 16 0 How is thatt air? 37 A Well# it doesn't account for C e metabolism 18 of carbon tatrachloridoe it doesn't ai count for the 19 excretion of carbon tetrachloride# it doesn't account 20 for the exhalation of these two compol ds or in 21 this case carbon tetrachloride in th expired air, 22 it totally eliminates the considerat:1 ns for the 23 excretion of these materials from the Uahuman body, 24 whion are generally pretty efficient . 25. These average daily doses* and I'm going to 8744 r, ' 1 refer to doses as both inhalation and .Agestion, 2 for Steve Starling, I think the point . . the total 3 there is point three four? 4A It would be point three four ligrams per 5 kilogram . 6 Q Both by inhalation and ingestio4? 7A That is correct . 8 9 In the highest yeart 19777 9A That is correct . 10 Can you relate that type of do go, daily donagat 11 to any of your animal studies or any 0 the animal 12 studies with which you are familiar as they deal 13 with carbon tetrachloride? 14 A well, that dos* would never pro uce liver damage 15 lot alone call death in any of the an mal studies i that, 16 I have ever conducted or in any of th literature 17 that I'm familiar with . One needs t got up to 18 60 milligrams per kilogram per day or thereabouts 19 in order to produce those kinds of li or damage* 20 either the call damage or the product on of the SGFT 21 or $GOT . 22 Q We discussed how pervasive car on totrachlorida 23 was in our civilization . Have you a an a National 24 Institute of Health document that tol s us really how 25 much the ordinary human being is expo ad to carbon 3745 1 tetrachloride and/or chloroform? 2 A Yen., I have . 3 0 What is that document called? 4A It's called Chloroform, Carbon retrachloridep 5 and other Halomethanes in Environmenta Assessment# 6 and it's published by the National Aca emy of Sciences 7 9 8A When was it published, do you k ow? 1978 . 9 0 Does that document indicate what the National 10 Academy of Science perceives to be the exposure 11 of the ordinary human being in-the United States 12 to carbon tetrachloride and chloroform? 13 A Wellp it does several calculations and comes. 14 up with a number of values, but I recall one being 15 around 900 milligrams per year, I believe it was, 16 for carbon tetrachloride . It will take me a minute 17 to find it if you want the exact number . 18 I'm sorryp that was for chloroform . For an 19 adult man it's 629 milligrams per year and for 20 chloroform it's 984 milligrams per ye r . 21 Tell a* what type of exposure hey are talking 22 about . Is that just for one year or is that for 23 more than one year? What are they s ying in that 24 docuzent7 25 A That's per year, That's the xposure to thosa MA*Arials D*X Year, 8746 1t- 6-1 0. 2 A. By whom? I am sorry . I don't understand 3 Who is being exposed to that am ount? 4 MR . GILREATH : Excuse me, Could you 5 quote the page number? 6 THE WITNESS : The page num r is 7 1801 8 ~QO Is it a specific person, or is it a group 9 of people, or in it the whole United States? 10 A . Thin would be the whole United Stateal not 11 referring to any specific personp but it would be 12 the whole United States, 13 Is that purportedly from the various compounds 14 that you described to me that are being produced 15 for the general public's use? 16 As Yeal and also through the chlorination process 17 of water in which you create chloroform . So it would 18 be an a result of food contaminationp water contamina- 19 tion and air . 20 as Did Dr . Rodricks make any assumptions# 21 let's say# with regard to Steve Sterling concerning 22 his total exposure of 290 milligrams per kilogram 23 for the year 1977 as shown in 2xhibit 327? Do you 24 know if he made any assumptions concerning what risks 25 Mr . Starling might have from consuming that? 8747 r, ~ I 1 A Yes . 2 0. What did he say about that? 3 Ae Well# his estimation was that t tore was a 4 ton percent increase in risk for Mr . St arling for that 5 particular level of exposure . 6 0. Did he confine it to the level that was in 7 that year alone? 8 A, Yes . He confined it to the tot cumulative 9 don* for that year# which was 280 mill me per 10 kilogram . 11 MR* GENTRYs Would you mark this? 12 (The document above referred to was 13 marked Exhibit 4970 for identification .) 14 (By Mro Gentry) Doctor, -did y u take that 15 assumption 16 MR . GILREATHt Excuse me . me, Breaux# 17 what in the number? 18 THE CLZRXs 497, 19 QO (By Kr* Gentry) Did you take I chat assumption 20 and look at other documents and anothei I exhibit and 21 do some calculations an it related to I ~hatassumpticn? 22 Ae Yost z dido 23 00 Tell me what you did? 24 A. Okay, What I did is I took th4 underlying 25 assumptions for Dro RodrickzI model, is which he 748 6-3 1 estimated a ton percent risk for Steve ;terling . I 2 subsequently took the dosesp the cumuli :ive doses 3 that were estimated for D, Johnson and Jo Maness and 4 calculated the risk based upon a 10 pe cent risk 5 for Steve Sterlinge which would have b on 8 percent 6 and I percent for the latter two . The I went to 7 the OSHA permissible exposure level fo carbon a tetrachloride, which is 10 parts per million# and 9 using the same assumptions of the Val of air taken 10 in by Steve Sterling that Or, Rodricks used& I calculated I I the amounts of carbon tetrachloride that will be taken 12 in bv an averaae worker in a onst-vear o riad of time . 13 I used that cumulative dose ., that is th amount he 14 would have taken in for a period of one year# used 15 the same risk estimator that is the son procedure# 16 and calculated the risk estimate for th average 17 1 worker* 18 Q6 Did you also go to a document t t dealt with 19 volsicol filter operators? 20 A* Your I did . 21 00 22 Ae Was that Kro Retzol6a exhibit? loop it wasp and I used again t a same assumption . 23 00 Now# those calculations do not ivo validity 24 to the cumulative exposurep do they? 25 IAO so# they certainly do not, 49 6-4 2 0 . And actually, as far as you are concerned well# withdraw that . 3 What result did you find using the type of 4 extrapolation that Dr . Rodricks used? 5 A* Well* if we were to use the assumptions that 6 Dr . Rodricks used and use the unusual procedure for 7 estimating risk which he usedv I have calculated using 8 those assumptions that there should be nearly a 9 hundred percent cancer amongst the workers who are 10 exposed to carbon tetrachloride at the OSHA standards 11 within two years and that they should more than all 12 of them have cancer by the and of three years* and 73 using the Velsicol filter operators as another 14 oxamplep within one year? 62 percent of them should 15 have cancere and within two years# a h dred and twsnty-~, 16 four percent . 17 go Did you hear the epideniologi &I study that 18 Dr* Shindell did with reference to the heptachlor works s? 19 A* Yesp I did, 20 go Is there any indication that these percentages 21 are indeed correct? 22 A* To the contrary* there in no i dication that 23 there in an inardaned incidence . 24 MR, GENTRYs Your Honor* would 25 I move that this be admitted an ;n exhibit 8750 1 6-5 1 2 to Dr . Harbison's testimony, THE COURTt All right . 3 (Exhibit 497 received in e vidence,) 4 Q0 (By Mr . Gentry) Is this a prop or way to do 5 a risk assessment? 6 As No, air, it's not . 7 00 How do you go about doing a ris k assessment a undo r these circumstances? 9 A, The way a rimk assessment is co nducted is to 10 use the daily exposure levels and to ex timate the. 11 risk for a given population of people hat is based 12 upon the daily exposure level one woul estimate the 13 risk of occurrence or the increased li alihood of 14 occurrence of a cancer in a thousand, hundred thousaLd 15 or a million people# and expressing it as a percentage 16 is a very unusual way of estimating th risk, 17 Q9 Doctorp looking at the highest daily dose 18 for Steve Sterling, Daniel Johnson and Jimmy Maness 19 look at that if you would, please . 20 As This in for carbon tetrachlorid e? 21 00 The combination, if you will? 22 As of carbon tetrachloride and ch oroform? 23 Q6 Tom* 24 As Okay . 25 Q6 We are still referring to Exhib it 327f are we 8751 I note Sir? 2 A, Yoe . 3 Do you have an opinion to whi ther any of 4 those three have an increased ri'I :k in C ncer as a 5 result of the daily doze which is shown by the plaintifgal 6 ova expert? 7 A, 8 go Yost I have an opinion . What is that opinion# Sir? 9 A. My opinion in that there is no eased 10 risk of cancer at those doses, II Is that an opinion based upon y expertise 12 as a pharmacclogistr toxicologistr an t in 13 Cancer? 14 Ao Yes, it is . 15 go 16 AO Is that with a reasonable madi Yost it is with a reasonable m certainty? Cal 17 certainty . 18 MAo GENTRYs That's all . our Honer . 19 THE COURTs Can we take a hort recess 20 and come back at 11007 21 will that be satisfactory with 22 everybody? 23 MR, GILREATHs Yost air . 24 (Recess .) 25 THE COURTs -Go ahead# Mro Gilreathe 875 ,,- I - 7 1 CROSS EXAMINATION BY MR . GILREATH : 2 3 Dr . Harbison, I was looking at four CVO 4 Exhibit 352, Have you published any -- do you have 5 any publications that deal specifically with the I 6 carcinogenesis of carbon tetrachloride and chloroform? I 7 A, That deal specifically with the carcinogenicity :, 8 testing of carbon tetrachloride and chl 3roform? 10 ~ Q6 I A, 11 Q0 Yen . Nov sirp I do not* Do you have any publications th at deal 12 specifically with the toxicology of car bon tetrachlorido 13 and chloroform* specifically? 14 A6 Yesp I do . 15 00 What is that? IsIhat on your C V? 16 A, Yes# it is . 17 Q6 What number? 18 Ae I ast sorry, I don't have it be Eore me . 19 MR. GENTRYs May I hand it to him? 20 MR* GILRZATHs Yes* 21 (Document handed to the wi tness .) 22 THE WITNZSSs There is Number 81 which 23 says# ORole of biotransformatio m in the 24 potentiation of halocarbon hop : toxicity 25 by 2t5-hezaaedione** The two stances that 8753 81 2 3 4 5 6 7 8 were used there were carbon tat achloride and chloroform . Those were the hal carbons, Then number 84, 'Potentiat on of chlorinated hydrocarbon toxicit by 2g5hexanedione in primary cultures of adult rat hapatocytes .' The halocarbons are the ch lorinated hydrocarbons in that case where chloroform 9 and carbon tetrachloride, 10 00 Excuse me, What is hex& 11 A . HexaAadione? 12 yes, 13 A, Hexanedions is a keton*0 which is the 14 substance that we were looking at, that class of 15 compounds, as to how they potentiate th e effects of 16 carbon tetrachloride and chloroform . 17 0 . What is a ketone? 18 A, A ketone in a chemical that has a double 79 bonded '0" in it . Keton*s can be used as solvents . 20 Q* Are they used in everyday thing s that people 21 use? 22 A* I am not aware of their conten a in household 23 products, I believe they are primaril used for indus- 24 trial purposes* 25 Q9 Have you done any work in the otentiation of 9154 9 1 carbon tetrachloride and chloroform With 1#32 butacedion? 3 Ae Butanedion? 4 yes, B-u-t-a-n-e-d-i-o-n -- Is that the 5 way you spell it? 6 A, I don't specifically recall, W looked at 7 about ton compounds, and I an sorry* I o not recall 8 that one, 9 00 Do you know what I am talking & :iout -- 10 11 A, Butanediol? 12 QS 13 A* Butanediol, Have I done any? 14 go Do you know what that is? 15 A* Yes# air . 16 00 What is it? 17 A* It is a butane that has two double banded 18 oxygens in it . It's a diaketone, 19 00 20 A* Diaketone . What is it used fox? I do not know, 21 00 Is it not a fact that the rDA has approved 22 this as a flavor solvent in foods? 23 As X am not aware of that . 24 Q* Let me show you an article the was published 25 in Toxicology and Applied Pharmacology and ask you if 87S5 C .10 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 you have ever seen that? A . yen . I am familiar with the work . QO Is that a recognized publication in the field of toxicology and pharmacology? A, Year it is . 0 . Have you ever seen that particular article before? A . I am familiar with the work of B, L, Hewitt, I know him quite wall, yes, Q . Thor* he did a study# did he not, of the potentiation of carbon tetrachloride b the 1#3-butanediol - how do you pronounce thatf Doc or? Butadiol? A* Butanodiol . Q* Is that what he did? A. Yes, air . Q9 And 1 .3-butanediol is a substance that is used in what, food# facd emulsifiers? Ao It says that butanediol is used as a flavor solvent and has an indirect food additive in packaging films* gaskets and adhesives, 00 And he found in his study# did he notp that carbon tetrachloride is potentiated by 1+3-butanedial? AO He says that it enhanced the hapatotoxic effects# that9a correct . MR . GILREATS : We would like to have 8756 that filed as an exhibit, your Ronor, 2 TEE CLERKs 499, 3 THE COURT& All rightg sir . 4 MR . GENTRYs Is that 498 or 499? 5 MR* GILREATH : 499 . 6 (The document above-referred to was 7 8 QO marked Exhibit 499, for identification .) (By Mr . Gilreath) This question saysp wHowever ;~ 9 the most significant use of Boo as they call it, is 10 an a synthetic source of dietary calories for supplsmazt~_ 11 tion of human and animal diets .0 12 Then I assume if a person in ingesting carbon 13 tetrachloride and also ingesting lt3-butanedioll, 14 that that would potentiate carbon tetrachloride 15 toxicity? In that right, a fair statement? 16 As Well# that paper concludes that based upon 17 the administration of some dosage of carbon tetrachloride 18 to the animals . I don't recall exactly what that was, 19 MRo GILRZATHs Your Honor# I move that 20 that be received in evidence . 21 THE COURTt All right, 22 (Exhibit 499 received in evidence .) 23 00 (By Mrs Gilreath) I believe it says in the 24 heading up there -- just read that into the record about 25 the dosage? 8757 1 A, Okay, *Pretreatment of rat3 Wit 1#3-butanediol 2 (1 .0v 5 .0r or 10 .0 percent in drinking ater) for 3 seven days enhanced the hapatotoxic, bu not the 4 nephrotoxic effects of a single dose of carbon 5 tetrachloride (0 .1 milliliter per killogramp ip) in 6 a does-related manner .0 7 00 8 A* Enhanced the hepatotoxic, did i say? The hapatotoxic, 9 The hepatotoxic means liver? 10 A, Liver damage . 11 QO And you say you know the author or the authors 12 of that article? 13 Ae You, I do, 14 Q0 which on*7 15 A, William Hewitt . 16 Q* Who is he? 17 A, William Hewitt was a postdoctoral student 18 with Gabriel Plaa, and I believe he in now working 19 for a drug company, Howeverp he used to .be at the 20 University of Kinsouri# and Gabriel Plaa was one of 21 my mentors at the University of Iowa, 22 00 Is Dr, Plan. also one of the authors of that 23 article? 24 A* Yen# air, Gabriel Plaa WA : th chairman 25 of the Department of Pharmacology t t e University of 8758 1 Montreal, and I believe he in now a Vic% Dean or 2 Dean of the University . 3 00 Is he the president of the professional 4 association that toxicologists belong ta? 5 A* Yes, He in the president of the Society 6 of Toxicologyp that in correct, 7 qMR . GILREATEs Would you nark this as 8 an exhibit# please? 9 (The document above referred to was 10 marked Extdbit 500v for identification .) 11 (By Mr, Gilreath) Dr . Harbison, I will show 12 you what has been marked Exhibit 500, which in 13 entitled 'Short Communication - Potentiation of 14 Carbon Tetrachlorid*-Induced Hopatotoxicity by 1#3- 15 Butanediolvl and ask you if you recognize this an 16 an authoritative work in the field? 17 As Yes# I do, 18 0 . Does that deal with the same subject as the 19 previous exhibit? 20 A, Yeso it does, 21 MR* GILREATHs We would like to have 22 that introduced into evidence . 23 ,THE COURTs All right* 24 (Exhibit 500 received in idenceo) 25 (By Mr, Gilreath) If lt3-butan:iol potentiates 8759 1 carbon tetrachloride -- you were explai ing earlier 2 the difference between potentiate and a norgistic 3 or synergism? 4 Under potentiation your basic t esis or the 5 basic promise I believe that you gave w a that a 6 substance might not have any capacity t do damage 7 unless it potentiatede is that the way ou put it? 8 A, No, The substance itself, like butanediolo 9 does not have the ability or may not he o the ability 10 to produce the damage itselfg and that t exaggerates 11 the toxicity of the chlorinated hydroca ban# or the 12 revorse of that, So one has an action nd the other 13 on* does not . 14 And did I understand you to say that you have done 15 studies on the synergistic effect betwo n carbon tatra-I 16 chloride and chloroform? 17 A . Yang air . 18 Q4 19 A, How many studies? Let me clarify* I have done at dies with 20 carbontatrachloride and chloroform not coking at the 21 two substances togothorp but looking at other substances 22 which enhance the toxicity of either on of those 23 materials . 24 Q9 Ohe I see, You have not done a udies, putting 25 then together$ just the two of then? 8760 r-, 1 As No, air, I have note 2 And the substances which you have done were 3 what -- with carbon tetrachloride? Lot's take carbon 4 tetrachloride . 5 A, The ketones . 6 Xetones? 7 A, 8 Q* Yes, air, In 1 .3-butanediol a ketone? 9 A* I think I have already said thatyes it wasp 10 but it is a diol . it in actually a two oxygent but 11 it's an alcohol -- it's not a ketone, Xt has two 12 hydroxyl substitutions on it . 13 00 Has Dr, Hewitt done any work in the potentiation: 14 of chloroform or carbon tetrachloride b katone*7 15 A, I believe he hasp yes . 16 (Document handed to Mr, Centry) 17 While he is looking at those# D . Harbieonp 18 when you did your study of the effec+. o ketone on 19 carbon tetrachloride# did that cause an potentiation? 20 A* Yes# it did . 21 Q* How is that relevant to this caiev this 22 study7 23 A* Well# I think it's relevant in that# as I said 24 before* the two classes of compounds thit cause potentia. 25 tion are alcohols, like butanediol, and like hexanedion, $761 1 which we studied, and to the best of my knowledge, 2 those are the only two chemical classes that cause 3 potentiation of the carbon tetrachlorid and 4 chloroform toxicityl not all compounds tontiate the 5 toxicity of those two compounds . 6 Q, Have you done any other studies other than 7 ketone yourselfs as far as potentiation of carbon 8 tetrachloride is concerned? 9 A, Yen* six . We have also looked at some alcoholf 10 some of the shorter chained alcohols . I don't recall 11 specifically which ones . We have look at about* 12 I would estimator ton different chomic in reference 13 to that, and I can find it here, 14 This in not an up-to-date curri ulum vita . 15 We presented it at the Society Of Toxicology 16 meeting last year, which is assentiall a study of the 17 structure activity requirements of alcohols and 18 ketones for the potentiation of chloroform and carbon 19 tetrachloride hopatotoxicity . 20 I also have a thesis -- a student has completed 21 a thesis on those studies an well, whi h has also 22 been published . 23 go Other than alcohol and ketones have you 24 performed any other studies insofar as the synergistic 25 effects on carbon tetrachloride and ch oroform or the 8762 potentiation? 2 A* The only other substances which we have 3 looked at are the sedative hypnotic, and we have 4 looked at -- I believe it was phenobarbLtOl . 5 Q* 6 A* All right, Any other? No, six . That would be it . 7 MR . GILREATUt I will ask hat this 8 be marked Exhibit 501 for ident fication . 9 (The document referred to a ove was 10 marked Exhibit 501, for identif cation .) II 0. (By Mr . Gilreath) Lot me show fou Exhibit 12 501, which is entitled -- it's an article from the 13 Journal of Toxicology and Applied Pharmacologyf and 14 is entitled "Acute Alteration of Chloroform-induced 15 Hepato- and Nephrotoxicity by Mirex and Kepone ." 16 I will ask you if that is an authoritative 17 paper? 18 Ae 19 Year it is . MR . GILREATEs I would off Br that an 20 the next exhibit in evidence# Y ~ur Honor, 21 THE COURTt All right, air a 22 (Exhibit 501 received in a vidence .) 23 THE WITNESSs If I could m mks one 24 addition -- actually, we did loo k at Mirex 25 and Kepone as well, which are i mcluded in the 8763 1 2 QO thesis . (By Mr, Gilreath) You looked a : the same thing 3 that is in this articlar Exhibit 501? 4 A, Yese 5 00 What is Hirex? 6 A, 24irex is a pesticide . 7 What is its chemical content? 8 A* It's a chlorinated hydrocarbon, 9 MR, GILREATHs I will ask that this 10 be marked Exhibit 502 for identification . 11 (The document above-referre d to was 12 marked Exhibit 502# for identif cation .) 13 (by Mr, Gilreath) I will show cu Exhibit 502t ; 14 an article from the Toxicology and Applied Pharmacology 15 Journal entitledp *Acute Alteration of Chloroform- 16 Induced Hepato-and Naphrotoxicity by a-Hexaner Hathyl 17 A-autyl Ketone# and 2,5-Hexanedions .1 18 Is that an authoritative articl b? 19 A* Year it is . 20 MR& GILREATUt I will ask that Exhibit 21 502 be introduced in evidence . 22 THE COURTs All rightp air, 23 (Exhibit 502 received in e vidence .) 24 MR, GILREATHs I will ask that this 25 be marked Exhibit 503 for ident Lfication . 8764 (The document above refer to was 2 marked Exhibit 503, for identi ation .) 3 0. (By Mr . Gilreath) T will show a exhibit 503#~ 4 an article from Toxicology and Applied armacclogys, 5 entitled Role of Biotransformation in Alterations 6 of Chloroform Repatotoxicity Produced Kepone and 7 Mirox ., 8 I will ask you if that in an oritative 9 article? . 10 A Yes, it is . 11 MR . GILREATH2 I will ask that that 12 be introduced in evidence, You Honor, 13 THE COURTt All right, si * 14 (Exhibit 503 received in vidence .) 15 MR . GENTRYt Your Honor, ; am not 16 making any objection to these itudies* I 17 am just curious, in light of the fact 18 that there is really no cross xamination 19 on any of these studiess, as to the status 20 of those studios in the record Are they 21 for the truth of the matter sp ken therein? 22 Are they for identification as authoritative 23 articles? We would just like At clarification 24 from the plaintiff, if the Cc t please . 25 THE COURTs All rights, a u end 1 2 3 4 5 6 7 8 9 10 11 12 13 . 14 15 16 17 18 19 20 21 22 23 24 25 8765 MR, GILREATHz Welle Your onorr the purpose of the article is Dr . B rbison has indicated he has done his c n studies in potentiation of carbon tetra hloride by certain compounder and it lc ks like that he has dome the same studies tt t thee* people haver and we are introducing tt so to show and X think he has already test fied -- that carbon tetrachloride is potentJ ted by certain other chemical compounds# whick include kepone and mirex and butanediolo whict in a food additive . That's the purpose c these articlesw 6-1 I 8766 1 MR . GENTRY : Your Honor* hat's finee II 2 with the exception that the but nediol I don't 3 believe is a food additive . I is an indir cti 4 food additive, which is substan ially differ:nt 5 from an active food additive . That's what 6 1 thought they were saying and I just wanted 7 to clarify that . 8 THZ COURTs All rightp 9i 9 BY MR . GILRZATHx 10 Howr did I understand you to a y on direct 11 examination,, Dr . Harbison, that carbo tetrachloride 12 and chloroform were not potentiated b chlorinated 13 hydrocarbon? 14 A By those chlorinated hydrocarb na which are 15 ketones they are . The chemical claa as that 16 potentiate the toxicity of chloroform and carbon 17 tetrachloride are ketones and alcohol is 0 All right . In butanediol an lcohol? 19 A Yes, air, it is . 20 0 According to this article, Exhi, bit 499r it's 21 used as a flavor solvent in foodp as In indirect food 22 additive in packaging films, it's usei as a food 23 preservative, and it's used as a food emulsifier . What do you mean by food emulsifier? 24 25 A I'm not sure what that means, I think alcoholi 6-2 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 8767 I in general are used to create stable a ulsionB and by adding small amounts of alcohols you c n change the emulsion qualities of various material . Q All right . In this article it says that "the in vitro binding" -- what does in vitro mean2 A It means outside of the organis *in vitro binding of carbon tetrachloridederived radioactivity to microsomal protein was increased both aorom- I can't A It's aerobically and anaerobic lly# I believe . Q Right . --'but was greater und r aerobic conditions . BD appeared to potentia a carbon tetrachloride liver injury, at least n part by producing an increase and/or alteration in mixe function activation of carbon tetrachloride to toxic metabolite ; .* Did you find that true in your studies? A Yen* sire we did . We found hat it was necessary to have a change in the met bolic activity to hav* .the potentiation occur for th carbon tetrachloride and chloroform . 0 'Thus, SD potentiation may ari a through several interrelated pathways ." Is that true? a Yes, I would agree with that . You did not do any tests to_dermino the $768 6-3 e~ 1 synergistic effect between carbon tetrachloride 2 you already said in chloroform -- nor did you do 3 any between, sayr toluene and carbon tetrachloride 4 or benzene? 5A No# air, I did not, because there would be 6 no reason to suspect that occurred . 7 Now, you were a part -- when did you do your 8 tests that you were talking about? A 9 The general ones of the chloroform and carbon tetrachloride? 10 a 11 Yes . A 12 Those studies began when I was at Vanderbilt . The student thesis probably developed over probably 13 the past five years, so I would estimate somewhere 14 around 1977f 978 . 15 That was about the time or it was about that 16 same time that you were a part of the task force in 17 this case, is that right? 18 A 19 That is correct . And you wore -- that task force had meetings 20 with AWAREO I believe? were you working for AWARZ 21 then or were you working for Velsicol? 22 A 23 0 24 Not sirf I was a consultant to WARE . And at that time was it Val ico Is intention did you talk to them about them do :ng Ia health study? 25 6-4 8769 1 A 2 Q 3 A Did I talk to them personally? Or did they talk to you or was it -Not Sir# to the boat of my recollection there 4 was no such discussion . 5 There was never any discussion that you know 6 about about Velsicol going to do a health study on 7 the people at Hardeman -- at Toone? 8 A Noe that discussion did occur# but it did not 9 occur with me specifically . 10 All right . Who did it occur with? 11 A Well# it was discussed amongst the task force 12 on several occasions and that's about all the 13 recollection that I have of that part cular matter . 14 Novp you have boon speaking th a morning about 15 carbon tetrachloride and chloroform o at least Xr . 16 Gentry has been talking in terms of at questions 17 would be carbon tetrachloride and chl roform used 78 interchangeably . Insofar an toxicit t are they in 19 t the same ball park or in the same -- 20 A They are similar, yeSe Sir . 21 Q So insofar an harmful effects are concernede 22 they are similar insofar as toxicity? 23 a Yesf sire they would be simila 24 Q He also -- or you went through certain principles 25 of the toxicology in your direct# and I'd like to go 6-5 8770 1 over some of those principles of toxicology with you 2 that I've kind of gone into . I'd like to show you 3 what's been marked as Exhibit Number 498, entitled 4 Principles of Toxicology . That is m own term -5 my own terminology for this . Looki g at Page 10 6 the first one is "Chlorinated hydroca bons are 7 manmade, and occur rarely, if ever, i nature .* 8 Is that true? 9A That's probably not totally tr a . There is 10 some evidence now that those compound in fact 11 probably do occur naturally and proba ly are created 12 in the troposphere as the result of i radiation . 13 0 So you would disagree at least to that extent 14 with that statement? 15 A Yes, air . 16 Q OExtensive experience and research with these 17 chemicals has led to an awareness that adverse health 18 effects can result from exposure to low concentrations 19 of these chemicals .* 20 A Yest sir . 21 0 That's true? 22 A Yes, it is . 23 a "We have also discovered that some of these 24 compounds also can cause cancer, birt defects and 25 possibly mutations after exposure to OW 6-6 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 8771 concentrations ." a I would agree with rbat . Q *In addition, these compounds a a hapatotoxic (toxic to the liver) ftephrotoxic (toxi to the kidneys) and neurotoxic (toxic to the central a d peripheral nervous system) .M A I would agree with that . Q On Page 2 : 'Calls that have b an damaged in nonspecific way invariably perform less well than normal cells, whereas cancer cells no only survive in competition with normal cells, but have a selective advantage over them .' Is that generally true? A Year Sir . Number 3 : *First, apidsaiolo ical methods are insensitive and may only detect a tramely large increases in cancer risk . The lower limit of detection by these methods has been a proximately a I 30 percent increase in cancer .' Does that sound okay so far? A Yes# air* wgvez a 10 percent increase in cancer would be unacceptable, although it would be undetectable in study of human populatioas .1 Is that 6-7 8772 1A I would agree with that . 20 "Second, clinical cancers only appear in humans 3 exposed to carcinogens after substanti al lag periods ; 4 typically on the order of 15 to 30 years .4 5A I would agree with that . 6 Number 4 : OFor the reasons st ated* animal tests 7 have become our principal source of in for=ation about 8 which chemicals pose a cancer risk in humans . The 9 animals most often used as models are rodentst usuallyii 10 rats and mice . Thee* animals are go d predictors of 11 human cancer riske although arguments can be made 12 that they are in fact not as sousitiv to carcinogens 13 as hU3&&n* .* 14 1 would agree with that . 15 We do know that these rodents,, then* are not 16 as sensitive to carcinogens as humans 17 A No . I think it says that an rgument can be 18 made . I don't think we can make gon, ral statements . 19 We have to refer to specific compound . 20 Q Okay . Number St eAnimal to t models are 21 used for two purposes . The first is to identify 22 chemicals which are capable of causin cancer# 23 regardless of the done . Properly do igned animal 24 studies use as their highest dose the maximally 25 tolerated dose, defined as a dose whi h causes no 6-8 a773 observable lethal or sublethal ti ijamage and 2 results in no more than 10 percen7u6s ht loss in the 3 exposed versus unexposed groups . Hig doses are 4 used in order to produce cancers at a ate high 5 enough to be detected with animal popu ations of 6 practicable size . If the substance i not a 7 carcinogen, and most are not# it will ot increase tunor 8 risk at any does . The only serious qaestion presented 9 in such modeling is whether a chemical can be a 10 carcinogen at a high dose but not at a low dose? I I i .e ., whether a 'safe' threshold exists . A great deal 12 of independent biologic evidence suggests that there 13 in no such safe threshold . The presumed mechanism 14 of cellular transformation discussed above supports 75 the same view and measurement of tumo risk 16 at low dos* levels is statistically i accessible to 17 practical determination . Second# th me tests aid in 18 estimating the extent of the increased risk of cancer 19 at low dosest given high dose data . These estimates 20 are made on the basis of mathematical extrapolations 21 of the high doses which have been sho n to cause cance 22 None of the several competing models f low do&* 23 extrapolation in use assume a 'safe' hreshold . 24 Disagreements on the proper model to at do not 25 involve whether the chemical can caus cancer at -- - - - - - - -- 6-9 8774 low doses ; such disagreements rather rtain to 2 how much cancer it can cause ." 3 Do you agree with that? 4A Yea, sirt I do . 5Q Number 71 "Animal tests are u ad to identify 6 chemicals which are capable of causing birth defects . 7 The animal tests are used in astimatin the extent 8 of the increased risk of birt There is a 9 better than 90 percent correlation be 10 substances which give positive and no tive responses in II these animal tests . Evidence based n the 12 techniques described above has shown t the inorganic 13 compounds, and the organic compounds luding 14 chlorinated hydrocarbons . . . are to and in many 15 cases are carainogenst toratogens and tagans .* T6 Do you agree with that7 17 A Yon, air& I would . 18 a Number as *Chloroform is an established animal 19 carcinogen causing cancers in several strains of mice, 20 in rats# and probably in dogs . Then aniaal models 21 have shown that the affected organs i clude the 22 liverg kidney and thyroid . Several pidomiological 23 studies on human populations exposed o chloroform in 24 public drinking water have shown corr lations between 25 chloroform and populatioA cancer rate: . on the basis 6-10 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 8775 of available animal and human data, exDosure to chloroform in drinking water increases the risk of cancer, birth defects and abortions .* Do you agree with that? A No# six* I do not . You do not? Number 9t "Chlorinated hydro arbons are known to cause -- are known to damage a liver, kidnoyr heart and nervous systems . Chlorinat d hydrocarbons i are suspected of causing cancer and bi th defects . On the basis of animal -- of available animal and human data, exposure of chlorinated hydrocar can in drinking water increases the risk of cancer, birth defects and organ toxicitiom .* Do you agree with that? A I don't agree with it in terms of its generality . It would have to depend an which compounds we are talking about . Q It would have to depend on what? A It would be compounds specific, that is which one* we wore referring to that might produce those changes . Q Say chloroform? A It would depend on the level to which the individual was exposed or the level of the water 8776 1 contamination . 2Q And you disagree with that as a general statement 3 about chloroform? 4A Ifellp I disagree with it in the sense that 5 it does not relate to the level of exp sure, and 6 unless I know what the level of exposu a is I can't 7 agree with the statement . 8Q Well, let's take the level of a posure on 9 Exhibit Number 375, which in the avora a concentrations 10 average annual concentrations in ppb o the Sterling 11 and Johnson wells and the Mosier well . Assuming 12 those levels of exposure# would you ag as with that 13 statement? 14 A Nop air# I would not . 15 0 We are talking about chlorofor levels in the 16 drinking water in 1978 of 950 and .970 ppb? 17 A That is correct . 18 Now, going back to number Be I t's take 19 number 8 first . What is there about number 8 that 20 you disagree with? 21 A Wellf I think that there has b an a change 22 conceptually regarding the toxicity p oducad by 23 chloroform and I would not agree, but again it's 24 going to depend on the level at which the chloroform 25 is in the water as to whether or not here might be 8777 1 some possibility of producing any of t ose effects . 1 2 Haven't you in the past testifi d to that 3 statement on Page S? 4A Yen# sirr I have . 5Q And where was that? 6A I believe that testimony was i . New Jersey . 7 I can't remember exactly . I believe it was Atlantic 8 City, Now Jersey . 9 And in making that statement h ve you changed To your mind since then? IT A Well# I agree that chloroform 9 an established 12 animal carcinogen . I agree with the statement that 13 it causes changes in mice and rats . 14 It causes cancer to several at ains of mice 15 and rats, in that right? 16 A That's correct . I do not agr e with the 17 statement about chloroform and its co relation with 18 cancer rates in humans . 19 20 21 22 23 24 25 8778 "l 1 Q . When you made this statement in now Jerseyl 2 what was the level of chloroform in the drinking 3 water that you were looking at there? 4 A, I can't recall . 5 0. Do you recall whether it was lo or higher 6 than the concentrations in the exhibit a on the 7 board? 8 A, I an sorry . I can't recall . 9 MR* GILREATH : Would you mark this 10 as an exhibit for identification? 11 (The document above referred to was 12 marked Exhibit 504 for identification .) 13 MR, GENTRYs May I see it? 14 (Document handed to Mr . Gentry .) 15 (By Mr . Gilreath) Do you recognixe that 16 exhibit? 17 As Yesp I do, 18 00 That is an affidavit which you filed in the 19 case in Now Jersey* is that correct? 20 A, That is correct, 21 Q. And on page 11 under OChlorofozz 22 Ao Yes,, air . 23 0 . Starting down about the third of the way 24 down on the righthand side of the page where it says# 25 Chloroform is an established animal rcinogen a -- C 8779 1 A. 2 Yes,, air . I see that . Would you read that to the and of the 3 paragraph for =e7 4 A, okay . 5 (Reading) OChloroform is an established 6 animal carcinogen causing cancers in several strains 7 of mice, in rats, and probably in dogs . These 8 animal models have shown that the affected organs 9 include the livere kidney and thyroid . Several 10 epidemiological studies on human populations exposed 11 to chloroform in public drinking water have shown 12 correlations between chloroform and population cancer 13 rates* On the basis of animal and human data# exposure, 14 to chloroform in drinking water increases the risk 15 of cancere birthdafects and abortions .* 16 ow Nows that's the same statement that is on 17 page 8 of the previous exhibit, is that correct? 18 As, That's right . 19 go How , you were looking at chloroform -- in this 20 case you war* testifying for the ZPAr is that right? 21 A, For the United States Department of Justice, 22 00 And in this case it involved a landfill in 23 Now Jersey? 24 A* That in corrects 25 And in that landfill they had_plluted the 8780 7-3 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 79 20 21 22 23 24 25 drinking water of some of the resident ? A, Well, actually it was pollutin water of Atlantic Cityp New Jersey . the drizAing W* AnCK in this case you were using p you and the government, you as the witness, were using the water quality criteria by the EPA as your standard? A . That in correct . Q6 And by the water quality criteria we mean what? A* The water quality criteria are levels which the U . S . EPA has generated which iden ify health risks that might be associated with ex osure to those for some period of time . 0 . All right . Now, over an page 14 of your affidavit is shown NEPA Well No* 1A*" Dayou see that? A, Yens, Sir . 00 And in that well in shown undo OChloroformg 68 ppb? A, That is correct* 0 . And your statement was# *This oval in approximately the 3SO times greater th n Water Quality Control standards .' Is that t us? A, That is correct . 00 And how many times greater wou d the 960- 8781 1 950 -- 950, rather, 1973 in the Johnsom and Starling 2 well be -- how many times greater than the Water 3 Quality Control Standard would that be? 4 A, The Water Quality criteria -- it would probably 5 be several hundred, 6 Q9 7 A, Well& 68 is 350 times? Yen# air . 8 00 ppb? 9 Ao Yes# six* 10 Q, And that's several times that, even# isn't 11 it? 12 A, well, that's 970 parts per billions so it's 13 a larger concentration* 14 00 Wqkllp the concentration in your wall number IA 15 on your affidavit was 68 parts per billion . 16 A, That's right, 17 00 And you testified in this case that that was 18 unsafe? 19 A* Wello X testified that the general composition 20 of the water for regulatory purposes was not safe 21 for continued consumption by the population of people 22 who would have been exposed# which in not only these 23 people, but the Atlantic City vaterintake, and it 24 includes a variety of other materials, 25 00 And on page 9 -- what is the a hibit number, 8782 1 the Principles of Toxicology -- what is your Exhibit 2 number on that? 3 A, That's Exhibit 498 . 4 04 498? 5 A, Yes, 6 0. On page 9 of Exhibit 498 is the statement 7 that comes from page 12 of your affidav tp does it a not? 9 A, Year air . 10 Q* Now, on page 14 of your affidav t you show 11 tatrachloroothylons at 9 ppb . 12 Ae Yes* sire 13 QS Xn Well No, lo which exceeds th Water Quality 14 Control -- water quality criteria? 15 A, That$s correct, 16 00 And than on page 15 you show i well No . 2 17 chloroform at 123 ppb -- that this lov 1 exceeds the 18 water quality criteria by 647 times . 19 A* That's correct, 20 00 What is the number of the exhi it for the 27 affidavit? 22 As That9s 504* 23 MR, GILREATH3 Your Honor we would 24 like to have Exhibit 504 intro uced in 25 evidence . 8793 THE COURTs All rightp eir 2 (Exhibit 504 receiv 3 as (By Mr . Gilreath) Would you re into the 4 record from page 11 under mChlorofozm* u to where 5 it ends with the word oSystem .0 6 A. I am sorry, I don't find 'Syst here . 7 00 Okay . We read the other, Let show you . 8 Ae I see . Do you want me to read rest of the 9 paragraph? 10 00 Yes, I I A* *Trichloromethans or chloroform a an industrial 12 solvent and chemical intermediate used n the production 13 of other chemicals . Chloroform is comp ately absorbed 14 when ingested in drinking water and is hen distributed, 15 throughout the body . The highest conce trations are 16 found in the peripheral nerves . Rats e posed to 17 chloroform have shown retarded develoomint and 18 reduced birth weights and in one study* an increased 19 rate of malformation was found, Chloroform sensitizes 20 the heajtp increasing the possibility of fatal cardiac 21 arrythmia (sudden death,) The lowest oses at which 22 this condition might occur are not kno n . At high 23 doses it in toxic to the liver, kidney and central 24 nervous system .* 25 Is that where you want me to stop? 8784 1 A, Yes* we already read the rest of that int 2 1 believep did we not? 3 A* I think that's correct . 4 00 So chloroform does attack the c entral nervous 5 system? 6 A* Chloroform has the pharmacologi cal properties 7 of being able to alter the function of the nervous 8 system, However, it does that only at high 9 concentrations, 10 00 Wall, you just stated here tha the lowest 11 dosage at which this condition might a cur are not 12 known, Is that true? 13 AO I believe that I was referring there to the 14 heart in the sensitization of the hearl tissue and 15 the production of cardiac arrythmias, 16 00 Well# you didn't say anywhere n this statementl 17 that this only occurs in high dosage, id yen? 18 Ae Nap sire I did note 19 Q4 Would you read into the record Paragraph No, 20 380 an page 19, 21 Ae Part of it is blurred out* Number 397 22 Q# Yes* 23 A, (Reading) 11 an concerned as scientist about the many contaminants and their uantJW 24 25 which have been identified in the wate surrounding 8785 .. and then it in blanked out - in my judgment 2 as a toxicologist, individual using Pr ivato wells 3 in the area of the landfill s :t:n :hCU d not be exposed 4 to then* chemical contaminants n ate used for 5 drinking or other purposes# such as ba hing, As is 6 evident from my previous observations, the presence of 7 most of these contaminants in public d inking water 8 supplies in any significant quantities would present 9 an extremely serious public health pro lem .* 10 Q, NOW# the short-term effects of he chlorinated I I hydrocarbons are irritation of the eye r irritation 12 of the throat# skin eruptions# contral nervous 13 syntax effects# depression - in that true? 14 A, wellf at certain levels of a 15 chlorinated hydrocarbon those things 16 is correct . to occur* that 17 Q0 well* if those things occur in the presence 18 of chlorinated hydrocarbons# then it wc iuld be 19 natural to assume that the levels of a; Were - 20 that the levels were enough to cause i .p would it notp 21 assuming you had those conditions? 22 A* No* air . Those conditions can be caused by 23 other things an well* 24 What are the long term effects of chlorinated 25 hydrocarbons? 8786 1 A* Welle the long term effects, ag. laino depending 2 on the done, might be organ injury, da age to the 3 liver . 4 as Injury to the respiratory syst m? 5 As That in a possibility . 6 as Injury to the blood forming sy tem? 7 As year air, 8 00 Injury to the nervous system? 9 A. Yes, air . 10 00 Now, that can occur as a resul of low level 11 exposure# can't it? 12 A, In general, those effects will be seen only 13 with high exposure$ and generally with chlorinated 14 hydrocarbons that are much larger in m lecular weight 15 than chloroform and carbon tetrachlori a . 16 Those things generally occur v th the higher 17 chain chlorinated hydrocarbons . 18 go Didn't you testify in the Pric Pit case 19 that these conditions can occur an a r sult of long 20 term low level exposure? 21 A, I don9t recall that testimony . I may have, 22 MR . GILREATH2 I will ask that thin C 23 24 25 be marked for identification . (The document above-r ed to was marked Exhibit 505, for id:nf ication .) :r 8787 I" , 1 0. (By Mr . Gilreath) Is that a coDy of your 2 testimony in that case, Exhibit 505? 3 A, Year it is . 4 Q* 5 A. Would you look at page 237 yes, 6 0. Look at line 13 7 OQ . Could you advise the court what such 8 short term effects generally are ir terms of these 9 toxic chemicals?* 10 And than read your answer . 11 A. (Reading) OA . The short term ffects would 12 be various irritations such as irritati a of the eyesp 13 the throato causing coughing, perhaps a in eruptions, 14 things like chloracne or pimples as a r sult of exposure 15 to various chlorinated hydrocarbons . G neral nuisance 16 irritation problems as a result of exposure which 17 lasts for a short term occur very moon after exposure .' 18 0* And the next question 19 00* Are central nervous system effects 20 also short term or acute effects?" 21 And then your answer . 22 A, (Reading) mA. Central nervous system effects 23 such as depression, unconsciousness or affecting 24 the central nervous system in one way r another to 25 impair motor activity would be a short term ef fect .* and 1 And the nextquestion -- 2 "Q, Now# in addition to the 3 Dr, Harbison, can you advise us what 4 or chronic effects may occur7w 5 Would you read your answer? 6 7 a 9 70 11 12 13 14 15 )6 17 19 20 21 22 23 24 25 8788 term effects, term effects 8-1 1 2 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 9799 A *The long term effects or chron c effects are generally thought of as being eith r specific organ injuries, such as injury to the aspiratory system or injury to the blood forming ystem or injury to the nervous system which ccurs as a result of long torme low level exposur to various substances . Examples of that might be lead oncephalopathy, an alteration of nervous system function as a result of long term, lo level exposure to lead . The other chronic effects that are of concern and that are generally tho ght of are birth defects or the production of birth do acts, which is known as a teratogen or toratogenicit . The production of mutations in genetic ma erial of germinal calls which will affect fut a generations and the production of cancer which wo ld be an effect on genetic material of somatic cells r all other, the *qq or the spernatozoa .' MR . GILREATH : Your Hono 1 we'd like to move that Exhibit 502 -- THE CLBRKt 505 . MR . GILREATEs .- 505 be admitted . THE COURT : All right . This in the last document you had reference to? MR . GILREATHs Yes . 8-2 6790 1or I 2 3 4 5 6 7 8 THE COURT% All right, si MR . GILREATHz Exhibit 505 is testimony in the United States District C Urt for the District of New Jersey . (Whereupon, the above-mentioned document was marked Exhibit Number 505 to th* testimony of the w tness and same will be found among the a hibits hereto .) 9 BY MR . GILRZATHi 10 9 Xcvf insofar an the water qual ty guide of the 11 ZPA is concerned for suspected carcin gone, which is 12 chloroform is one and carbon tetrachl ride under 13 their criteria, is'that right7 14 A That is correct . 15 Insofar as risk evaluation or risk determinatics 16 is concerned# no level is safe, that' what they say, 17 isn't that right7 18 A Well# the BPA says that there 3 no scientific 19 basis for any model for making judgme ts about 20 safety and, therefore# since there is no scientific 21 basis for that as an interim action t sy will assume 22 that there is no safe level . 23 0 And that's what you so testifi d in this 24 Price's pit case, that was your test mony7 25 A You mean did I testify that th water quality 8791 8-3 rl- 1 criteria were -- I'm not sure I unders tand your 2 question . 30 Did you not testify that method 3 do not now 4 exist to establish a threshold for a c Ircinogen 5 and that there is no scientific basis Ear estimating 6 the safe level# therefore there is no safe level 7 for a carcinogen in drinking water? 8A Well, air, I only testified in ~sference to the 9 compounds that were found in those wel Lsp which 10 include the longer chain chlorinated h. Fdrocarbons 11 like vinylchlorids, which included the chlorinated 12 benzenes* the naphthalenes . For thos. a substances 13 that is a different consideration . P )r carbon 14 tetrachloride and chloroform that is m )t a considorar-zor . 15 a Is not chloroform and carbon to rachloride 16 a suspected carcinogen? 17 A 18 Q Yes, Sir, it is . Then doesn't that quality contr )l guide apply 19 to those suspected carcinogens? Isn't that what it 20 says? . 21 A The water quality criteria, yes sire it does . 22 0 So if you applied that rule# th ne then there 23 would be no safe levels for carbon tetrachloride 24 and chloroform under that rul*? 25 A Under the rule of the water quality criteria, 8792 S-4 1 that's correct . 2Q And that's the rule that you wwre advocating 3 when you were testifying for EPA in thiit case? 4A Well# I was advocating that rulia based upon 5 a regulatory process to prevent the ut .Llization of 6 water by the city of Atlantic City tha,t contained 7 these materials . 80 Well, you wouldn't apply a diff,irent rule to 9 this Hardeman County situation, would :rou? 10 A Yes, air . I think there's a v,ary different 11 rule . What we are talking about is c.Lusation and 12 that differs significantly from rsgula~ tory standards . 13 MR . GILREATH : I think I Im about through ., 14 Your gonor . 15 BY XR. GIIJUATH : 16 Q Dr, darbisoup are you familiar 1with a study 17 involving a human being who was cleani:~g his gun with 18 carbon totrachloridep he had a couple 43f drinks and 19 caused a peripheral neuritis and there was a study done 20 on this person? Do you recall that s tudy? 21 A Noe sire I do not . 22 MR . GILREATHs That's all we have . 23 THE COURTt All righte si,ro 24 MR . GENTRY% Your Bonore I will be about 25 fifteen or twenty minutes on re,airect . 9-5 8793 1 THE COURT : All right . Do you want to 2 come back at 1%45? Will that be all right? 3 MR . GILREATH ; Can we f nish that now? 4 We have got a witness that needs to got 5 on after lunch . 6 MR . GENTRY : I don't see how that is going 7 to make a lot of difference if we are going 8 to break for lunch immediately afterwards . 9 MR . GILREATHS All righ 10 THE COURT : All right . 11 Coss .) 12 THE COURTz All right, Mz Gentry . 13 MR . GZNTRYs I'm waiting for Mr . Gilreathc 14 THE COURT-z Oh . okay . is MR . GENTRYs May we proce 0 Your Honor? 16 THE COURT% Year Sir . 17 REDIRECT EXAMINATION 18 BY MR . GENTRY's 19 Q or . Harbison, I'd like to take Exhibit 498# 20 which in entitled Principle* of Toxicc logy written 21 on top of the exhibit, and paraphrase the first one 22 a little bit# if I may . 23 Carbon tetrachloride and chlorciform are manmade 24 and occur rarely, if ever, in nature . 25 Is that true or false? 879 1A Wall, it's partially true and partially not 2 true . 3 Still talking in terms of carbon tetrachloride 4 and chloroform as opposed to chlorinated hydrocarbons : ; 5 Extensive experience and research with these 6 chemicals has led to an awareness that adverse health 7 effects can result from exposures -- exposure to 8 low concentrations of these chemicals, carbon 9 tetrachloride and chloroform . 10 What would you say to that? 11 A I would say that's not true . 12 0 mWe have also discovered that some of these 13 compoundso -- and let's just say that we have also 14 discovered that carbon tetrachloride and chloroform is also can cause cancer, birth defects and possibly 16 mutations after exposure to low concentrations . 17 A That is not true . 18 0 In additiong carbon tetrachloride and chlorofora 19 are hepatotoxic, naphrotoxic, and neurotoxic . 20 A That is partially true . 21 Q How many chlorinated hydrocarbons are there# 22 six? 23 A There are hundreds, thousands . 24 0 what's the difference between arbon tatrachlori 25 and chloroform and chlordans? 8795 1A The number of carbons in the molacula, the 2 amount of chlorine on the molecule, the basic structure 3 of the molecule# its physical properties, both its 4 physical and chemical properties . iI 50 The molecular weight? 6A Molecular weight is considerabl y different . 7 In the difference in molecular weight a 8 critical difference? 9A Yen . 10 Carbon tetrachloride and chloro form, are they 11 high molecular weight or low molecular weight 12 chlorinated hydrocarbons? 13 A They are low molecular weight . 14 a Dr . Harbison, tell me about thi s United 15 States versus Charles Price, at al . ihen did this 16 occur? 17 A Wellp I believe it was late 1979 or sometime 18 in 1980 . 1 can't recall the exact date . 19 Q And you wore a witness for whom? 20 A I was a witness for the United S tates Department 21 of Justice . 22 Q They were bringing an action under what? 23 A Under the Clean Water Act . 24 0 And they were basing their actio n against these 25 people on what? 8796 1A Well, on the changing of the qua lity of the 2 water that had been there and based upo n the use of 3 that water for public drinking . 4 Were they relying upon the water quality criteria 5 as set up by the EPA? 6A Yes, they were . 7 Do you discuss in your affidavit what the water ; 8 quality criteria means? 9A Yesp I do . 10 Where do you do that, air? I I 35? 12 A 13 Q 14 k I haven't found it yet . On Page 12 . Righte it's 35 . 15 Q 16 A Read that to the Court, pletase . wFollowing the passage of legislation in the 17 Congress, the United States Environmental Protection 18 Agency promulgated standards designed to ensure that 19 the American public is not exposed to dangerous levels 20 of toxicant drinking water . These standards arm 21 expressed in terms of risk analysis . While U .S . EPA 22 suggests that no exposure to carcinogens occur in 23 drinking water, it has expressed its standards in term 24 of estimated risks from these contaminants . Theme 25 estimates are based upon the scientific information to 8797 1 which I have previously referr d . Th water Quality 2 Criteria are expressed in term: of one additional cl 3 per one million population as a functi a of a 4 lifetime exposure to the particular ca cinogen . The 5 most recent publication of the standar a appear in 6 the Pederal Register on November 28, 1 80 and is 7 attached an Exhibit B to this alfidavi The 8 water Quality Criteria are a useful guide to risk 9 assessment from chemical exposure and will be referred 10 to by me in my analysis of data in th a case .' 11 Now, there is an exhibit that a the Water 12 Quality Criteriap is there not? 13 A That's correct . 14 Can you turn to Page 79323 of a Water Quality : 15 Criteria and read the first paragraph or the first 16 couple of sentences designated wRisk xtrapolation' . 17 A Okayr it's entitled "Risk Extr 0Xpolation*" 18 OBecause methods do not now ex st to establish 19 the presence of a threshold for carci ogenic effects# 20 XPA*s policy is that there is no sci ntific basis 21 for estimating 'safe' levels for car inogens ." 22 Do you want me to proceed? I~ 21 a Yesf Please* 24 A "The criteria for carcinog therefore, 25 state that the recommended concen:nr:,ion for maximum 3799 11 . 1 orotectioA of human health is zero ." 2 All right . Now, drop down to lealth Guidelines 3 in the next paragraph, and there's a pirase which 4 commences "The estimation of health" . Do you see 5 that? 6A Yeal I do . 7 Read thate 8A "The estimation of health risks associated with 9 human exposure to envixon=ental pollutants requires 10 predicting the effect of low doses for up to 11 a lifetime in duration ." 12 0 Are those scientific statements or policy 13 statements? 14 A Those are policy statements . 15 Are those statements directed to genotoxic 16 carcinogens? 17 A Yen, air, they art . 18 Q And what did you toll me a genc toxic carcinogen 19 was? 20 A A genotoxic carcinogen is one t hat is able to 21 interact with the genetic material of the call and 22 cause a change in that call to initia a cancer . 23 Q Would that be -- withdraw that question . 24 Do you have the transcript of 'a hearing in 25 front of yout air? a 8799 1 A 2 3 Yes, I do . Can you turn to Page 28 for me, please? Yes . 4 Do you see line 8 there? And Ill start with 5 the question, if I may, and I will let you answer 6 the questions . Will you do that with me? 7 A Yes . 8 Q *Now, we've described the tools which 9 toxicologists use in identifying probl ams caused by 10 chemicals . We've also talked about the results 11 from a toxicological standpoint in terino of their . 12 short term and long term effects . By the way, in 13 terms of long term offectso Dr . Harbis 2n, can you give 14 us a time frame? We talked about chr Daic or long 15 term, but what is generally meant from a toxicological 16 standpoint in terms of years?" 17 what's your response? 18 A I'm sorry, give as the page again . 19 a Do you have the transcript? Not your 20 affidavite the transcript . 21 A Yes# I have the transcript . 22 a 23 A It would be 26, as near as I c n see . I'm sorry, I thought you said S . 24 Q It looks like 28 and I believe it's 26 . 25 A Okay, Line 187 Mo Q 2A Yes . Okay . *For carcinogenicity o the production 3 of cancer# it is generally thought of to be fifteen 4 to thirty years . That is the time rom exposure 5 until the disease actually occurs . or mutaqenicity 6 it's thought to be at least tione which 7 would be approximately twenty-two yea S . And for 8 toratogenicity it could be anywhere f om a few weeks 9 to probably more like eight to nine m nths .* 10 9 Nowe before I read the next qu stion, I'd like to ask you, are we-referring to go xics there? 12 A Yes . 13 The next question is : 74 "In any event, Doctor, we have discussed the 15 tools that toxicologists use, the off cts that are 16 generally observed through the use of those tools . 17 I wonder if you could advise the Cour when one is 18 dealing with the human being or the h an system 19 what the entry points are that these hemicals may 20 attack or actually got into the body o cause the 21 typo of effects which we have just do cribed?* 22 A *Chemicals can got into the hu an system by 23 on* of three ways . They can be*-- It says observed, 24 but I'm sure that should be absorbed -- "across the 25 surface of the skin,, which is known a parcutan*ous 8801 1 absorption . They can be" -- again it says observed, 2 but I think it should be absorbed -- *from the 3 gastrointestinal tract view contaminants in food or 4 drink, and they can also be absorbed through the 5 respiratory tract if they are airborne either as 6 a mist or vapor or somehow suspended in the air .* 7 Now if you would turn over to P go 28, we 8 are talking about mechanisms for the p oduction of 9 cancer and the attorney questions you ; I 10 01 wonder if you could advise the Court what 11 those mechanisms are?" 12 A *Well, there axe at least two .' And one is a 13 genetic mechanism, the genetic mechanism being the 14 direct interaction of the chemical with DNA of various 15 cells of the body . The other mechanism is an 16 opigonatic mechanism and tumors or transformation 17 of calls into cancerous calls occurs as a result of 18 toxic recurrent tissue injury from exposure to an 19 irritant or son* chemical to produce various tissue 20 damage ." 21 a The chemical that produces the genetic 22 machanisme is that a genotoxic chemicaL? 23 A Yes, it is . 24 0 And what kind of chemical would produce the 25 opigenatic mechanism? 8802 r, 1 A That would be substances like carbon tetrachloride 2 and chloroform . 3 Is that testimony consistent or inconsistent 4 with the testimony you have given here today? 5 A 6 Q 7 A That testimony is consistent . Would you turn to Page 31, please, sir . Yom . 8 Q At the top of the pagep I believe it's Mr . 9 Walsh says : 10 *Dr . Harbison, you wore talking about the 11 routes in which chemicals can cause cancer in human 12 beings . I wonder if with reference to 408 you 13 could describe those various pathways?" 14 I'm assuming 408 was an exhibit . 15 A Yes, sir . 16 What is your answer there? 17 A OWhat we or* talking abouto two specific 18 mechanism* whereby chemicals can introduce cancer 19 as a result of interaction with the calls . The two 20 pathways or* one, a genotoxic pathway or genetic 21 time mechanism whereby the chemical i teracts with 22 directly with DNA . There in an into action which 23 which occurs with DSA to alter the go otic mixture . 24 so now the call is transformed into a n, ow call line 25 which is now uncontrolled and in grow h . The other 8803 1 mechanism, being enzymatic or a tissue injury pathway 2 as a result of chronic recurrent tissue, might occur 3 fro& trichloroothylone or other chloriaated hydrocarbon 4 solvents which produce various organ i jury such as 5 injury to the liver . The chronic re urrent injury 6 over a period of many years into the r pair process by! 7 chance alone, there will be spontansou mutations 8 which will occur which will again tran form calls 9 into a new call line which now become ncontrolled 10 in their growth . So both of these result in 11 transformation of calls to a now cell line ." it's 12 says l1ning, but I think it should be line . "The 13 hazard with the genotoxic o rganic path ay is only 14 a call, & single call, to tr4 15 7e DNA ., 16 I 17 18 19 20 21 22 23 24 25 04 00 13 that statement consi:t:nt.or inconsistent 2 with testimony you have given h r t da ? 3 A, That statement is consistent wl the testimonj 4 I have given here today* 5 go Turn if you will to page 50# at the bottomof 6 the page, and Mr . Walsh queries you as follows$ 7 "go With respect to chloroform 0 can you advise 8 the Court as to its toxic properties?* 9 Would you give me your answer thato please? A* (Reading) wA, Chloroform is it says UP - I don't know what that means -- oroform is 12 an up as opposed to the ethane* It is a single carbon 13 atom# and chloroform has boon around f r a long period 14 of time, Chloroform in a very potenti, 1 anesthetic . 15 It has very potent properties to depre a the central 16 nervous system, It was actually used or an extensive 17 period of time as an anesthetic agent . Nost recently# 18 and the reason It was discarded as an nesthatic 19 compound is because it sensitizes the eart tissue 20 to the compounds that are known as cat epolminest 21 and the cad ump c-a-d-m-i-u- F 22 are the materials that cause the hea: to beat fastere 23 and chloroform sensitizes the heart an those compounds 24 and causes an arrythmia . it results I very sudden 25 death as a result of the expos :6 vapors of 8805 9-2 chloroform# is one of the reasons for a andoning it 2 as an anesthetic .' 3 (Reading) *Q . Because it will fibrilate the 4 heart? A, (Reading) "A . Cause fibrilation and cause immediate death . It is also toxic to various organs . 6 it produces 7 8 as (Interposing) I expect that in hapatotoxic . A, 9 (Continuing to read) hapatotoxic*-- I think that sentence should be Olt produces hepatdnzicity . 10 It produces hapatotoxic .injury to the liver resulting in destruction of liver callsi resulting in extensive 12 liver damage, It also damages the kidneys and it is 13 14 a recognized carcinogenic as well as b ing a teratogen .sk I will ask you this# sirr with regard to that is statements Would it take a large or a all doze of 16 chloroform to create extensive liver damage? 17 A* 18 It would take a very large dose . 19 00 on the order of how many parts per billion or million# air? 20 As 21 It would take hundreds of thou ands of parts per million . 22 00 23 Would it take a large or small sa to damage the kidneys? 24 A, 25 It would be the same, It woul take a very 8806 e,~ 9-3 1 2 3 4 5 6 7 8 9 10 11 12 13 Id 15 16 17 18 19 20 21 22 23 24 25 large dose . Q . I will ask you to turn to page 0 of the transcript if you will, please . Mr . Wa sh asked you the following question# bottom of the p get "Q . Dealing with the actual we Or quality criterion as they affect human beings9 oes the water quality criterion itself indicate the w tar issafe to drink?* Nowe your answer, As (Reading) *A . Not the contrary, For those substances which are known carcinogens or suspect carcinogens there is a statement that no level is safe, But assuming a certain level of contamination the increased risk for cancer would be at a certain level, assuming consumption of the wat r at that level of contamination,* 0 . (Reading) 10 . You actually d al with the concept of the water quality criterion at paragraph 35 of your affidavit, 175 in evidencep do you not# Dr, Harbison?a A, (Reading) *A* That's correct 00 (Rsading) 00 . 1 wonder if yo could advise the Court and counsel what the risk fa tor is based upon and how Us S . EPA has COMO Up Wit the so-called water quality crit*rion?l 8807 (-- - 9-4 1 A . (Reading) *A . The risk factor is based upon 2 an extrapolation of animal data from a Ugh done to 3 a low dose . Through that extrapolation process the 4 risk factor is determined that basedupDn a certain 5 level of exposure there will be a likelLhood of 6 one or more cancers occurring for certaLn numbers 7 of population or for a certain number o people who 8 would be exposed to that particular con aminant in 9 the drinking water .* 10 00 Now, I am asking you this questlon exclusive 11 of the record to which we are referringp and by the 12 way# that recordp for our transcriptp is Exhibit 505, 13 Is that a lifetime exposure? 14 Ae That is a lifetime exposure, 15 00 Doctor, I have just one more area to query 16 you abouto If you will turn to page 78 of the cross 17 examination . Mr . Gladden asked you this questiont 18 OQ, You have testified at length about the 19 types of chemicals and their results on the human 20 calls, in fact, that some cause cancer mutations# 21 at cetera, Do we got into a problem of how much 22 dosage causes or has the kind of effects that you -k 23 have testified to on the cells70 Ci 24 And your answer? 25 A* (Reading) *Yen .* Sao 3 9-5 1 Q* (Reading) '0 . What kind of d0 3ages are we 2 talking about?O 3 A. (Reading) *A . For which effec t?* 4 (Reading) "0 . Well, let's tak e the first one, 5 For the cancerous things .0 6 A, (Reading) "A . For the cancer affect dependingi 7 on whether it is a genetic pathway or a genetic action 8 orepigenatic pathway# probably as we have already 9 pointed outg maybe only one molecule, That doesnOt 10 seen very probable, but certainly that is a workable 11 hypothesis . For the recurrent tissue in jury we would 12 havato have enough exposure to provide or to produce 13 some sort of organ injury . Sop for example, trichloro- 14 ethane or some of the smaller molecular weight 15 chlorinated hydrocarbons# it would be a much larger 16 dose .' 17 QO (Reading) *Q . Does the dosage also affect 18 whether the results on the calls are acute or chronic 19 in nature?" 20 A* (Reading) *A . It can# yes .0 21 0 . (Reading) "0 . 1 notice that th e water policy 22 criteria talked about a lifetime situati on, what does 23 that mean?* 24 A* (Reading) "A . It means ingesti on of that 25 material for the lifetime of the individ ual .' 8~09 00 (Reading) *Q . Well, I am a la man . I have 2 a little trouble understanding that . A e we saying 3 that if a person throughout his lifetim we take 4 the normal life -- what, sixty years, s venty yearsop 5 something like that?" 6 A, (Reading) OA . Yes,* 7 QO (Reading) OQ . Is that what is done to 8 create this standard, ingest the chemi al involved 9 for a lifetime, then he is exposed to he risk of on* 10 in a mi .Uion or whatever the test comes out to be?" A* (Reading) OA* That in correc 12 00 Dr . Harbisonp were there aorta n wells that were involved in this lawsuit? 14 A, Yes, 15 00 Before we got to thate there w s some reference 16 to your putting into evidence in that ranscript a 17 flow chart or something that described the genctoxicity 18 route as opposed to the other routs, th recurrent 19 injury routs . 20 A, Yes, 21 09 Do you remember what that looked like? 22 A* Yes, I do, 23 00 Do you have one of those with You? 24 A, Yesp sirt I don 25 QO And what is it contained? 8810 1 A. That chart is contained in the book that we 2 has put together for the U*S* EPA, entitled *Toxicological 3 Evaluations# Risk Assessment and Safety Determinations 4 for Chemical Exposures,* 5 00 Do you have more than one copy of that book? 6 A, No* air* I only have the one, 7 as Would you turn to wherever the flow chart is 8 located, if you villp plase? 9 As That flow chart in located bet son page S5 10 and S6 . 11 QO Would you hand it to me so I may show it to 12 opposing counsel first . 13 As All rightp air, 14 MR . GENTRYs With the Court's permission# 15 may I hand this particular chart to the court? 16, THE COURTi I see what it looks like, 17 It looks awfully complicated . Maybe he can just 18 describe what it is, 19 MR* GENTRYs All rightp Your Honor, 20 as Tell me what that chart shows# if you will# 21 please# Dr, Harbison? 22 As Wells the chart shows that a substance is 23 metabolized or chanqed from a parent compound to a 24 metabolite# and that metabolite can result in tissue 25 injury or produce cancer as a result c an spiganotic 8811 1 pathway, or it can bind to DNA directly and cause 2 cancer by ganotoxic pathway, and it goes on to describe, 3 the various kinds of damage that would be produced 4 an a result of that metabolic transformation . 5 Q. You referred to tissue damage as far as that 6 chart in concerned . Isthat the man* thing an call 7 death? 8 A. Yes, it is . 9 Q, Does that chart describe the type of compounds 10 that you think carbon terachloride and chloroform are? 11 A* Yes# it does . 12 QO What does it say about those tic compounds? 13 A* Well# it 14 Q* (Interposing) I know it doesn't refer to those 15 two compounds specifically . But what coos it say 16 about them? 17 A, That the opigenetic pathway in the pathway 18 by which carbon tetrachloride and chlo oforn produce 19 recurrent call damage and call death a d can resuk 20 over a prolonged period of time in the production 21 of cancer . 22 a* Is that chart in any way contr ry to your 23 testimony that you have given here tod y? 24 A* No, it in not . 25 HR . GENTRYs Would you ma a that entire 8812 1 volume an -- we seem to be putt ng in things 2 by books* Your Honor -- so I wo ld just 3 standardize the procedure and a k the court 4 to admit the book as Exhibit 50 with the 5 understanding that that chart is contained 6 between pages 55 and 56, 7 THE COURTt All right . 8 (By Mr . Gentry) Would you mak that an 9 exhibit for identification? 10 (The document above-refer ad to was 11 marked Exhibit 506, for identi ication .) 12 (By Mro Gentry) Just so I und ratandp I 13 will ask you again -- what is that boo ? 14 A, This is the back that we have repared which is is entitled 'Toxicological Evaluation : Risk Assessment& 16 and Safety Determinations for Chemical Exposures*v 17 It was prepared for the United States Environ- is mental Protection Agency for teaching his course 19 to its people and the Department of Pu lic Health 20 ,persons in the southeast, 21 00 Anywhere in that book do you dviso the 22 ZPA to use a percentage an a risk ease 8MOAt? 23 A* No . air . 24 Let as ask you to turn your at ention for a 25 moment to Exhibit S04, and let's just go to the first 813 9 .10 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 well on page 14 of 504 . A* Yes . 0 . 1 notice there are inorganic co poundsand organic compounds in that well? A* That*x correct . I 00 Of the organic compoundag an I correct most of them are chlorinated hydrocarbons# but not all? A* That is correct . 00 How many parts per billion of hicrinated hydrocarbons do you have in that first well? A* Welle I roughly added it up, a d it is about 140#000 parts per billion . ; a, of all chlorinated hydrocarbons? A, That is correct . Q . of which chloroform represents how many parts per billion? A* 68 parts per billion, 00 Now, you are not counting the Inorganics in there, are you, six? A* No$ I am note 04 What is the largest combinatio of chloroform and carbon tetrachloride in the worst ear on Zxhibit 375? Ao Wellp it looks to be about 10p OOr and I would say 40 or SO -- 10,,350 parts per billion . 8814 1 00 2 A. of Of chlorinated hydrocarbons . 3 Q. When you look at the organic cc pounds in well 4 No, 1# are there some or many heavy mol cular weight 5 chlorinated hydrocarbons# I should have said few or 6 many* 7 A* There are -- compared to carbon tetrachloride 8 and chloroform, there are many which have a higher 9 molecular weight . 10 Turn over to page 150 and let9s look at the inoi11 ganics on well Mo . 2 just for a minute . 12 I notice they have arsenic# 31 arts per billion 13 there, Is that a known human carcinoge ? 14 A, Yesp air . Arsenic is a known h an regulated 15 cancer-causing agent . 16 00 Are there any other of those heavy metals 17 that are known regulated human carcino *as? 18 A, I an not sure, a Cadmiumr maybe, 19 I an not really for sure about that* don't think 20 it is on the list of known . 21 Q* What was the United States ask ag as it related 22 to these wells, what was their positio as it related 23 to these wells? 24 A* My understanding of the positi n of the United 25 States Department of Justice is that i was asking for 8815 1 a new water supply to these people who mad contaminated 2 wells and was further asking for some rslief to the 3 possible intake of these materials into the Atlantic 4 City water supply, and that reli f w: :t:n the form 5 of moving the water intake for :he of Atlantic 6 City to some other place such that it d not 7 take these materials into it . 8 00 Were the people still ingesting the water 9 from those wells at that time? 10 A, To the best of my knowledge I lieve they wore . 11 00 Doctor, in light of the cross aminatioup 12 I an going to ask you one question, on more question, 13 What is the scientific reason for your astimony that 14 there in no risk of cancer in these pec le who ingested 15 the waters as we see them in Exhibit 31 16 A, The scientific basis for my tag imony considers 17 the mechanism of action of carbon tetra Imloride and 18 chloroformi that in what we knowt both bout its 19 metabolism and its interaction with ce3 and parts of 20 calls . Both carbon tetrachloride and c roform 21 Are not converted to metabolites which t*ract with 22 DNA* They could not possible form subs 2 which L.- 23 interact with DNA to lead to initiatior of cancere 24 and# further, based upon our occupatior 1 experience 25 with carbon tetrachloride# and chlorofc up which has a $816 long history, there is no evidence that these two substance : 2 have resulted in an increased incidence of cancer# 3 and, furtherr based upon our extensive xperience with 4 the use of these materials as therapeut c agent 5 in the pharmacutical adiences, again th re is a long 6 continued history and safe use of these materials 7 for the treatment of a variety of disea a% so it is 8 based upon my knowledge of the mechanis of action 9 of these materials and also based upon air 10 past incidence of use . tCr end MR . GENTRY : Thank you . Dr . Harbison, 12 that in all . 13 14 RECROSS EXAMINATION BY MR. GILREATHz 15 0 . Doctor, looking at Exhibit 13, .s toluene 16 a genetic or apigenetic carcinogen? 17 A, I don0t believe that there in v, Iry much 18 evidence regarding the carcinogenicity of toluene . 19 I couldn't answer that question* 20 21 22 23 I 24 25 8817 Q How about benzene? 2 A Benzene* There is certainly a idence that 3 benzene can be metabolized to a metabo ite which couldl 4 bind to DNA . It can be metabolized t an apoxide, it~ 5 certainly has that potential . 6 9 And naphthalene? 7A Naphthalene, my response would 3e similar to 8 that for benzene . Certainly has the lecular 9 configuration whereby it could be biot nsformed to 10 a compound that could bind . II a All right, That would make th 0 theno 12 under your definition, a genetic carci gen as opposed ; 13 to an apigenatic, is that right? 14 A Yes, air . My opinion about t t would be 15 that those would be much more likely ; be genotoxic 16 agents . 17 a All right . Now, it you take genetic 18 carcinogen such as those two, than yo have the 19 potential for what you call the on*-h t mechanism, 20 don't you? 21 A Well# I don't call it the on*- it mechanism . 22 There certainly is a hypothesis that uggesta that . Q- ; 23 A single chemical can interact with a single strand 24 of DNA to cause transformation of a c Up and certai 25 naphthalene and benzene, based upon t air molecular 10-2 Baia 1 configuration, could have that potential . 2Q Look on Page 32 of your testimoay at Line 71 3 the questions 4 "This sometimes" -- 5A I'm sorry, I haven't found it yet . 6Q Okay . I'm sorry . 7A Page 32? 89 Yes . 9A Yes . 10 *This sometimes called the one-hit hypothesis? I I A.NSWZRz That is correct .' 12 A Yes,, air . 13 Q Nov, the one-hit hypothesis is Outlined 14 in your affidavit on Page 4, is it not, under Number 15 117 16 A Yost. six . It says in theory, that's correct . 17 That's what you are talking about tlieke is the 18 on*-hit hypothesis . Would you read that, pleas*? 19 A *In theory, it might take only a single 20 molecule of chemical to produce a mutation in the DNA 21 of a body call . A single chemical molecule in a 22 liter of water would have an extremely small possibilit 23 of causing such change, but when a chemical 24 contaminant reaches the level of detectability it iS 25 present in a liter of water in a number of hundreds of 8819 1 trillions or quadrillions of molecula3 tGn to t1he 2 fourteen or ton to the fifteen molocul as . What saams . 3 an insignificant exposure, tens of par ts par billion, 4 for example, is in reality an occasion for an 5 *norm us number of damaging encounters between a chemical 6 carcinogen and its DNA target in body -ells . It is 7 in this way that very small exposures :an lead to 8 damage ." 9 There you are talking about the concept of 10 causing cancer without first causing imjury? 11 A That is correct, that is the direct binding 12 of the substance to the DNA . 13 May I see your green book there for a moment? 14 All righte looking at Exhibit 506# on the left 15 is your spigenetic mechanism, is that right? 16 A Yost Sir . 17 All right . Now, in your opigonotic mechanism 18 you assume that there is some repair and regeneration? 19 A Yen . 20 Q All right . Now -- and that there is no 21 immunosuppression? 22 A That is correct . 23 Q Now, this thesis that you are a vocating therst 24 then -- and I'm reading from the book n carbon 25 tetrachloride and other -- chloroform and carbon tetra 882~ f, 1 the National Research Council book . s that the one 2 you read from earlier? 3A Yen, it is . 4 All right . Let me show it . on Page 167 5 187, excuse me, there wrers it says, 0 he threshold 6 model' in the third paragraph down . 7A 8 Yes . "The threshold model assumes a me critical 9 level of exposure below which the car inogenic process! 10 will not be" -- is that word initiate ? 11 A Yes . 12 *The arguments in support of n affect levels 13 generally center around the concept of roper 14 detoxification and adequate repair sy tem, including 15 DNA repair and immunosuppression .0 16 So if those -- that thesis ass es that there 77 is an adequate repair system, and so orth, is that 18 right? 19 A That in correct, 20 M.R . GILREATnt That's a 1 we have . 21 MR . GENTRY : Pirstj Your Honor, may I 22 inquire of Mr . Gilreath if tha Is our book 23 that's in Possession of the wiZess? 24 MR . GILREATH : Yes . 25 MR . GENTRY . I have jus, two questions, $821 ~1- 1 Your Honor . 2 REDIRECT EXAMINATION 3 BY MR . GENTRYi 4a Doctor, I will show you Exhibit 357, which is a 5 run down -- 6 MR . GENTRY : If the Court pleases . 7 I'm marry . 8 THE COURTt Yes, air, go right ahead . 9 BY MR . GZNTRY : 10 0 .- which is a run down of the Sterling and 11 Johnson wells made by ERM, look at 10 and 12, 12 and tell me if you can find bousene in any amount 13 in that particular exhibit in wither the Johnson 14 or sterling well? 15 A 16 Q 17 A 18 9 19 A No# I do not find it . Do you find naphthalene? In the Sterling well? Yes . Yes, 20 Q All right, Do you find any r ading abov* your 21 reference ton parts per billion? 22 A No# I do not* 23 Q What's the highest? 24 A The highest is six point three parts per billion . 25 a Are there any mondetectablos thers? 8822 1 A 2 Yes, there are . Turn ovez to the Johnson well, L f you will, 3 please . 4 A Yost I find naphthalene . 5 Q 6 A Any above your reference ten parts per billion? ! No . 7 0 What 's the highest? 8 A The highest is two point seven parts per billion . 9 0 Any nondetectables? 10 A Yes, there are . 11 MR . GENTRY : All right, ti auk you . 12 That 's all, 13 MR . GILREATHz That's all we have . 14 THE COURTi All right . You may stop 15 downt please . 16 MR . GENTRY : If the Court p leases# may 17 Dr . Harbison be excused? 18 THE COURT% Any objection* Mr . Gilreath? 79 MR . GILREATH : No . Your Ho nor . 20 THE COURT% All right . 21 (Witn ass excused .) 22 MR . GENTRY : If the Court pleases . 23 THE COURT3 Yost 21r . 24 MR . GENTRYz May it be allowed for Mr . 25 Hanson to leave the table? He's going to 8823 1 to take Dr . Harbison to the pla e . 2 THE COURT : All right, s r . 3 MR . GENTRY : Your Honor, a have a couple 4 of housekeeping matters which m y or may not 5 be mooted by some previous stat meat concerning 6 how -- Exhibits . 7 Excuse me, Your Honor . I seems that I 8 have to give the keys to someon 9 THE COURTz All right . 10 Mr . Wharton . 11 (Whereupon, an off-th -record 12 discussion was had .) 13 THE COURTs All right, Mr Gentry, T4 go right ahead . 15 MR . GENTRY : Your Honor, era is an 16 exhibit 388 which contains a st pulation between 17 the parties . That is the rat or bulky 18 exhibit that contained the vari us headline* 19 from newspapers . 20 THE COURTs Yes . 21 MR . GENTRYs No have not read the 22 stipulation into evidence . T in was accepted 23 into evidence and the better p rt of valor 24 prompts us to ask the Court if the stipulation 25 and the documents contained th rein art indeed 8824 1 in evidence for the purpose for which they 2 were stipulated . 3 THE COURT : It is for th Court, because 4 if you were to undertake to rea that I would 5 certainly help you find the sol tion to the 6 problem . 7 MR . GENTRY : Thank you, Y~ur Honor . 8 That was a housecleaning job we wanted to make 9 sure was finished . 10 THE COURT : Yes . 11 MR . GENTRY . We have one ther item to which 12 the Court can direct its attent on and, under 13 the Rules of Evidence as we und retand themp 14 take judicial notice . It is a portion of the 15 rederal Register dated January 4, 1983f 16 which announces a partial administrative stay 17 with reference to the identification and 18 classification and regulation of potential 19 occupational carcinogens . That was the result 20 proffered of the colloquy -- I mean we this as 21 a result of the colloquy the other day as to 22 whether or not there was -- whether it had been 23 cancelled or whether it had been put in some 24 kind of limbo, and we find that the proper 25 words at* partial stay . 8925 1 A,nd we would proffer this for tne Court's 2 perusal . 3 THE COURT : All right . 4 Any objisctiont xr . Gilreati? 5 MR . GILREATH : No, Your H nor . 6 THE COURT : All right . 7 MR . GENTRY : We would lik to mark it 8 as an exhibit . 9 THE CLZRX : It will be NU or 507 . (Wher6upone the above mentioned document was marked Exhibi Number 507 12 to the testimony of the wi nos* and will be 13 found among the exhibits h reto .) 14 MR . GENTRY : I'm about to utter words that 15 I suspect will be of great reli f to the Court . 16 That completes the defend t's defense . 17 THE COURTz All right, si It is a joy 18 to bear those words . Of cours there axe 19 words that could be more joyful . 20 But I had better be seriou on the record, 21 Kre Gantry* The Court underst nds . 22 Xr . Gilr*atho it's up to y u to say 23 something . 24 MR . GILREATHs we are ready to go forward 25 with our rebuttal . 1 2 3 4 5 6 7 8 9 10 11 12 ~113 14 15 16 17 18 19 20 21 22 23 24 25 8826 THE COURT : All right . I take it there are no motions or anything at this point? MR . GENTRY : Wellp Your Honor, there are some motions that we would like to make . I was almost referring then to make a suggestion to the Court that perhaps as it relates to the proposed rebuttal proof we should have parameterso I can visualize a retrying of the plaintiffs' case if true rebuttal is not adhered to, and I don't know whether the Court has really THE COURT : Mr . Gentry, a week or so ago you all heard me tell a fine man standing there that the Court could not presume that the Internal Revenue Service would not follow the law . Well, I certainly can't presume that able lawyers such as Mr . Gilreath and Mr . Wildee, and Mr . Garrety will not follow the law and tho rules that apply any more than I could presume that you or Mr . Spxagins or Mr . Mitchell would not follow the law . So I think the Court has to assume that until the Court's assumptions are demonstrated to be misplaced assumptions . MR . GENTRY : The simile is well taken* 1 Your Honor . 8827 1 2 THE COURT : Thank you . 3 MR . GENTRY : I understand 4 THE COURT : The other thi it seems 5 to me, is that it might be help ul for us to 6 go ahead and complete the proof in this case . 7 Then if it becomes necessary do n the road, 8 we can take up really any motions that might be 9 necessary, and you have that flexibility where 10 it's a nonjury trial . 11 MR . GENTRYz Very well, our Honor . 12 With that suggestion from the ourt, we will 13 not proffer our motions at thi time . 14 THE COURTt All right, a r . And I think : 15 the Court ought to state on th record that 16 neither side waives anything 17 MR . GEXTRYt Thank you, our Honor . 18 TIIk COURTt -- in accepti g the Court's 19 suggestion . 20 MR . WILDERs Your Honor, I have one 21 housekeeping matter too . Wh n I was reviewing 22 the transcript last week prior to Mr . Wade's 23 testimony, I was going back, :nd looking at 24 Exhibit 276 that had been i oduced for -- 25 I thought as an exhibit intro uced into the 1 record, but possibly there was caveat I 2 put On the introduction of it b Mr . Spragins . 3 This is the real estate notaboo of Mr . Murdaugh a, 4 and I believe the caveat was th t if he saw 5 any objection he would make it . If not, 6 it would go into evidence . au I did not 7 officially move it into evidenc after Mr . 8 Murdaugh's testimony and I woul like to do 9 that at this time . 10 THE COURT : All right . In there any 11 objection at this point, Mr . Go try? 12 MR . GZNTRYz I will defer to MR . Spragin#, 13 if the Court please . 14 THE COURT3 All right, Sir . 15 MR . SPRAGINSt I haven't thought about it 16 for several months* Your Honor . My recollectioi, 17 is that I didn't have any objections . 18 I will toll you for our% in th morning . 19 MR . WILDER$ Very well, our Honor . 20 THZ COURT : Welle suppos we go ahead 21 and admit it subject to whatev r Objections* 22 if anyt Xr . Spragins might con up with . 23 KR . SPRAGINS : That in & 1 right . 24 MR . WILDAR : Thank you . 25 (whereupon, the &bov -referred to $829 1 document was marked Exhibit Number 276 2 to the testimony of the witness and same 3 will be found among the exhibits hereto .) 4 MR . GARRETYs If the Court please* call 5 Dr . Scott Clark . 6 THZ COURT ; All right, Sir . 7 Do you gentlemen want Dr . '.lark sworn 8 again? I don't think it's necessary* 9 MR . GENTRYs So necessity for thatt Your 10 Honor . 17 THE COURT : All right, air . 12 13 14 15 16 17 18 19 20 21 22 23 24 25