Document KzeVvq90p8D2nzdKw780eXKwx

7 1 York, Binghamton, New York; Master's degree in 2 radiation biology, University of Rochester in New 3 York in 1955. I began -4 Q The Master's was in what discipline? 5 A The university called it radiation biology. It's 6 more accurately radiation safety. I began work 7 with Dow Chemical September 1st, 1955, as an 8 entry-level industrial hygienist and radiation 9 safety specialist. 10 In 1960 I transferred to the Texas 11 division as chief industrial hygienist, returned 12 to Midland in 1962 as an industrial hygienist in 13 the same laboratory situation. In 1970 I became 14 safety and industrial hygiene manager for the Dow 15 Midland division, now called Michigan division. 16 Q That was in '67? 17 A I said '70. 18 Q '70? 19 A Yes. In 1971 I went back to health and 20 environmental sciences as an industrial hygienist. 21 1976, I transferred to the Dow Badische Company in 22 Williamsburg, Virginia, as director of industrial 23 hygiene, returned to Midland in 1978 as manager of 2166 V ' 3 l3lG>3 8 1 industrial hygiene research and manager., of the 2 industrial hygiene lab. 3 MR. WAGNER: That's B-A-D-I-S-C-H-E. 4 A Then in December of 1979 it catches up to where I 5 transferred to Dow Corning. 6 Q From 1970, if my numbers are correct, here, from 7 1971 to 1976 you were present or employed at 8 Midland, Michigan, correct? 9 A Yes. 10 Q And from 1971 through 1976, in your capacity as an 11 industrial hygienist, did you have any 12 responsibility for industrial hygiene in the 13 manufacturing process for 2,4-D or 2,4,5-T or 14 Silvex or their components? 15 MR. WAGNER: I object to the form. 16 A To the best of my recollection, I had no primary 17 responsibility for manufacturing operations during 18 that time period. 19 Q Do you know who would have had responsibility for 20 the industrial hygiene aspect of the manufacturing 21 process for those chemicals? 22 MR. WAGNER: Same objection. 23 A You are challenging my memory, of course. I 2167 9-2.2.&1 9 1 believe about 1972 Dr. Ralph Langner became the 2 Michigan division industrial hygiene manager, so 3 he would have had the basic responsibility for 4 that. 5 Q Dr. Ralph? 6 A Langner, deceased. 7 Q L-A-N? 8 A L-A-N-G-N-E-R. 9 Q What was his position during thattime period, if 10 you know, with the company? 11 A To the best of my memory, he was manager of 12 industrial hygiene for the Michigan division, was 13 the title. 14 Q You mentioned thisMichigan division before. What 15 was the Michigan division? 16 A It's the productiondivision of DowChemical 17 located in Midland, Michigan. 18 Q Do you know what other divisions are located in 19 Midland, Michigan, other than the Michigan -- 20 A It's corporate headquarters for the company, so 21 there are many corporate offices and functions 22 going on there. 23 Q Have you ever seen a flow chart or a diagram of 2168 10 1 the corporate organization in Michigan?, 2 MR. WAGNER: At any point in time? 3 Q During the time we're talking about, between '70 4 and '75? 5 A I don't remember. 6 Q Who would your boss have been between 1970 and 7 1975? 8 A Harold R. Hoyle. 9 Q And if memory serves me correctly, Dr. Hoyle was 10 head of industrial hygiene in the seventies? 11 A Yes. 12 Q From 1970 to '75, how many industrial hygienists 13 were at Midland, Michigan, involved in the 14 manufacturing process? 15 MR. WAGNER: I object to the form. 16 A Wow, there may have been four or five, but not 17 full time, to my recollection. 18 Q Okay, when I spoke with -- have you reviewed the 19 deposition of Dr. Rowe? 20 A No. 21 Q Dr. Rowe mentioned that he thought, in the 22 industrial hygiene division in the seventies, 23 there were ten to 15 industrial hygienists. Does 2169 P-2.2-bC, 11 1 that refresh your recollection at all? , 2 MR. WAGNER: Let me object to the form. 3 That question is different than the one you've 4 asked, but -5 A It doesn't help a whole lot, because I was trying 6 to remember as best I could, you know, from my 7 personal experience, and I gave you my best guess. 8 Q That's fine. Who were the other four or five 9 industrial hygienists that you recall back between 10 1970 and '75? 11 MR. WAGNER: Let me, as a point of 12 clarification, because it's the problem with your 13 initial question then followed up by Dr. Rowe, you 14 initially asked about hygienists involved in 15 production, and then made reference to Rowe's 16 answer about how many industrial hygenists in the 17 industrial hygienists' division. I don't know if 18 that's a greater number, but is your question how 19 many industrial hygienists were there in the 20 safety and industrial hygiene department, separate 21 and apart from whether or not they were involved 22 in the production end of it? 23 MR. SCHULER: Correct. 2170 12 1 A You fellows have thoroughly confused me. Would 2 you restate the question, please? 3 Q What I'm trying to find out, Mr. Silverstein, is 4 what was the number of industrial hygienists that 5 worked under Dr. Hoyle from 1970 to '75? 6 A That's a bit clearer, and I think my four or five 7 is the best I can do. 8 Q And as head of industrial hygiene during that time 9 period, Dr. Hoyle -- was industrial hygiene part 10 of the biomedical research lab? 11 A Oh, another memory stretcher, it was part of the 12 biochemical research department when I joined in 13 the fifties. Somewhere in the time period you 14 mentioned the name was changed to health and 15 environmental research, I believe. Biochemical 16 research is not biomedical, careful distinction. 17 Q I understand. Who did Dr. Hoyle report to between 18 '70 and '75, if you know? 19 A Dr. Don D. Irish, for part of that period, anyway. 20 Q Is Dr. Hoyle still alive? 21 A Yes. 22 Q And where is he located, if you know? 23 A Probably on the eighth tee about now. 2171 P'safes' 13 1 Q Not in Midland, Michigan? 2 A Delray Beach, Florida. Actually it's too early 3 for the eighth tee. 4 Q Now, to get back to my other question, other than 5 yourself, who are the other four or five 6 industrial hygienists in the department? 7 A To the best of my recollection, Arnold Schaffer, 8 S-C-H-A-F-F-E-R, Richard D. Olson -- 9 M R . WAGNER: O-N or E-N? 10 A O-N. The D is important because there's a Richard 11 A. there, too. George Florez, I believe was one 12 of our group at that time, and Edward J. 13 Schneider, S-C-H-N-E-I-D-E-R. Oh, Donald Rapp, 14 R-A-P-P. 15 Q Did any of these individuals, Mr. Schaffer, Mr. 16 Olson, Mr. Florez, Mr. Schneider, Mr. Rapp, have 17 responsibility for industrial hygiene in the 18 production of Silvex or 2,4,5-T or 2,4-D? 19 A To the best of my recollection, each of those 20 folks had some responsibility for some area, but 21 no one had total responsibility for the Michigan 22 division. 23 Q When you say each had some responsibility, do you 2172 14 1 recall what the breakdown of that responsibility 2 was? 3 A No. 4 Q What were your duties and responsibilities in that 5 time period between 1970 and 1975? And if they 6 changed, let me know that, too. 7 MR. WAGNER: I object to the breadth. 8 A My recollection of that particular time period is 9 that my main effort was in two projects. One was 10 called Dow Environmental Health Services, a 11 consulting-for-fee effort to offer industrial 12 hygiene and a number of other services to 13 industry. I was the lead industrial hygienist for 14 that effort, which was headed up by Arnie 15 Schaffer. 16 The other role I played was as chief 17 health physicist, which is radiation safety 18 officer for the Dow Nuclear Services program, 19 which offered Dow services to the nuclear power 20 industry. 21 Q Now, back in the 1960s, and I have some memoranda 22 here that I'm going to show you in a minute, you 23 apparently were given some responsibilities with 2173 15 1 regard to doing some industrial hygiene, work 2 regarding the process for the manufacture of 3 trichlorophenol, correct? 4 MR. WAGNER: I object to the form. 5 A Yes. 6 Q Who initially assigned you those responsibilities? 7 A Harold R. Hoyle. 8 Q Do you know why you were selected for those 9 responsibilities ? 10 A I could only guess, conjecture at this point. 11 Q I don't want you to guess, but if you've got a 12 reasonable estimate, I want to hear it. 13 A I was a good industrial hygienist, and I was 14 available. 15 Q Okay, sounds reasonable. And prior to.being given 16 the responsibilities or assigned some 17 responsibilities with regard to the production of 18 trichlorophenol and potential TCDD contamination, 19 what were you doing before you were assigned those 20 tasks? 21 MR. WAGNER: I object to the form of the 22 question, no predicate. 23 A To the best of my recollection, in the early 2174 D- 2-11 16 1 sixties I was doing industrial hygiene in the 2 Midland division production plant, and doing 3 radiation safety for the division and for the 4 company. 5 Q Were there any industrial hygienists prior to your 6 assignment in the sixties that had been assigned 7 to the production of trichlorophenol in' terms of 8 monitoring the safety of the workers in that 9 production? 10 A I do not remember. 11 Q What was the reason -- well, let me go back. Your 12 first assignment in that area was approximately 13 what year, do you recall? 14 A 1964. 15 Q Before 1964 had you ever had any responsibilities 16 with regard to industrial hygiene for the 17 production of trichlorophenol? 18 A Not that I recall. 19 Q Or 2,4,5-T? 20 A Not that I recall. 21 Q Silvex? 22 A I don't remember. 23 Q Or 2,4-D? 2175 17 1 A I don't remember that either. 2 Q Had you worked at all with the industrial hygiene 3 aspect of the production of any agricultural 4 chemicals prior to 1964? 5 A I don't remember specifics on that. I may have, 6 but I just don't recall any specific project. 7 Q Had you investigated any cases of chloracne prior 8 to 1964? 9 A I think one time, yeah. 10 Q And do you recall when that was? 11 A Sometime, oh, a year or so before, maybe. 12 Q About 1963 or so? 13 A Roughly, yeah. 14 Q Prior to that time had you investigated any cases 15 of chloracne at any Dow plants? 16 MR. WAGNER: I object to the form. 17 A Not to my recollection. 18 Q Prior to 1964 or '63, do you know if there was any 19 individual industrial hygienist that was 20 responsible for monitoring the production of 21 trichlorophenol or 2,4-D, 2,4,5-T or Silvex? 22 MR. WAGNER: I object, asked and 23 answered. 2176 Q'ZX13 18 1 A No. 2 Q No, you don't know? 3 A No, I don't know, if I understood your question, 4 yeah. 5 Q Okay. In 1963, when you were first asked to 6 investigate a case of chloracne, what was that in 7 connection with, what process? 8 A It was a different process called Dow 6-X. 9 Q And what is it the 6-X stands for? 10 A I believe it stood for hexachlor -- oh, my 11 goodness, hexachloro, I want to say phenoxy, but 12 that doesn't fit, because you can't put six 13 chlorines in that. It was a hexachlorophenolic 14 compound that I cannot name for you at this point. 15 Q And did you write any reports with regard to that? 16 A I don't remember. 17 Q Now, when you were assigned by Dr. Hoyle to 18 investigate chloracne in 1964, how did you proceed 19 to do that? 20 A Well, I visited the plant to observe the actions 21 of the employees, which is the standard initial 22 step in industrial hygiene investigation. 23 Q So you went to the plants, themselves? 2177 D- 19 1 A I spent quite a bit of time in that plant, yeah. 2 Q Did you actually have an office in the plant? 3 A No, I didn't have an office in the plant. 4 Q What else did you do? 5 A Proceeded to do some air sampling and wipe testing 6 of the plant environment. 7 Q Anything else? 8 A I'm pretty sure that I issued a quick report, 9 because we had an urgent situation, so I must have 10 written a report. I don't remember for sure. 11 Q Anything else that you recall? 12 A I'm not sure what you want, but if you give me a 13 specific -14 Q I'm not sure what you did. That's why I'm asking 15 the question. 16 A Well, that was phase one. Is there a question on 17 the floor? 18 Q If that was phase one, what else did you do, what 19 was phase two? 20 A My recollection is that my next assignment was as 21 safety officer in the plant, with the 22 responsibility for assuring safe operation. 23 Anything that happened in the plant, I had to 2178 20 1 specify safety precautions and make sure people 2 followed them. 3 Q When you say in the plant, what are you referring 4 to? 5 A The building housing the production process. 6 Q Referring to trichlorophenol? 7 A Specifically. 8 Q Was there more than one physical building that 9 that applied to? 10 A No. 11 MR. WAGNER: That -- 12 THE DEPONENT: I'm sorry, I -13 MR. WAGNER: That's all right. So we're 14 clear, you meant was there more than one building 15 producing trichlorophenol? i. 16 Q Other than the building that he had responsibility 17 for, right, producing trichlorophenol? 18 A Either way, the answer is no. 19 Q That's what I understood your answer to be. What 20 was the building number, do you recall? 21 A It was 199 building. 22 Q And after becoming asafety officer and 23 instituting safety precautions and making sure . 2179 21 1 there was compliance, was there any other duty 2 that you discharged in connection with the 3 responsibility to review industrial hygiene for 4 trichlorophenol manufacture? 5 A I was involved in a number of things in that whole 6 situation, both some laboratory studies and 7 investigating other buildings in the division, and 8 I just do not remember timing, you know, on that, 9 but I do remember that I was wandering around 10 doing other duties, as well. 11 Q Is one of the things that you did to check 12 exposure levels of the workers in the* plant to 13 TCDD? 14 MR. WAGNER: I object to the form. 15 A Well, that was one of my responsibilities, yes. 16 Q And was it one of your responsibilities to correct 17 operating procedures where excessive exposures may 18 b e .occurring? 19 MR. WAGNER: I object to the form. 20 A At what time period now? During my health officer 21 duties, yes. 22 Q Okay. And was it part of your duties and 23 responsibilities to identify areas where 2180 t> 3377 22 1 difficulties with exposure may occur? 2 A Yes. 3 Q And did you also serve as kind of a liason between 4 the toxicology department and medical department 5 and production? 6 MR. WAGNER: I object to the form, 7 vague. 8 A Yes. 9 Q Prior to 1964, had there ever been a case of 10 chloracne in a Dow worker working with 11 trichlorophenol that you're aware of? 12 A No. 13 Q Prior to 1964, were you aware of any case of 14 chloracne in a Dow worker working with the 15 finished product of 2,4,5-T? 16 A I do not remember. 17 Q Or Silvex? 18 A I don't remember. 19 Q Or 2,4-D? 20 A I don't remember. 21 Q In the course of your career at Dow Chemical, are 22 you aware of any cases of cancer in Dow workers 23 that were exposed to trichlorophenol in the 2181 0-A278 23 1 manufacturing process? 2 A No. 3 Q Same question with regard to 2,4,5-T? 4 A No. 5 Q Silvex? 6 A No. 7 Q 2,4-D? 8 A No. 9 Q As a practical matter, back in 1964, with these 10 workers that came down with the chloracne, how 11 would you first become aware of that? Would they 12 go to the medical department first, to report this 13 before you became aware of it? How did that work? 14 MR. WAGNER: I object to theform. 15 A The answer is yes,theywould have gone to 16 medical. 17 Q And somebody, would somebody inthemedical 18 department then contact you to make you aware of 19 the problem? 20 A No, theywould have -- 21 MR. WAGNER: Iobject tothe form, calls 22 for speculation and vague as to time. 23 Q How would you come to be aware of the problem? 2182 Q -rn 'i 24 1 MR. WAGNER: Same objection. 2 A From Harold Hoyle. 3 Q So the medical department would contact him? 4 MR. WAGNER: Same objection, calls for 5 speculation. 6 A Yes. 7 Q And then he would tellyou,and then you would 8 investigate it, is that the way it would work? 9 MR. WAGNER: I object to the form. 10 A Ye s . 11 Q How many cases, to your recollection, of chloracne 12 were there from the exposure to trichlorophenol in 13 1964? 14 A I don't know, for a particular year, how much we 15 had. 16 Q Can you give me an estimate, to the best of your 17 recollection? 18 A Before theevent, about 60,as I recall it. 19 Q Did you have occasion to see each one of the 20 workers that came down with the chloracne? 21 A I don't remember that. 22 Q Did the workers that came down with the chloracne 23 continue to work in the plant generally, or were 2183 1 2A 3Q 4A 5Q 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 25 they transferred somewhere or what? They continued to work in the plant. Do you recall the names of any of the workers? Wow. Just one. Who was that? MR. WAGNER: Let me stop you for a moment, because I'm concerned about the medical privilege, and in releasing confidential medical information about that person, and I have not yet gotten a direction from Dow as to whether or not they want pursued by certiorari or not the court's decision to require release of those names. I don't -- Dick, why don't you go ahead. At this point I'm going to instruct you not to answer, but I'm going to ask you to let me know the person's name before we get out of here today, and I won't restrict Mr. Schuler from asking you questions about that person, what he was doing, what position he had, anything else he wants to know, but for the moment let's not reveal his name. MR. SCHULER: My position is we've got a court order saying we can have the names, and the 2184 26 1 addresses, as well, and phone numbers. He says he 2 knows one of the names, and there's no stay been 3 entered based on any petition or writ of 4 certiorari, so I think it's a violation of the 5 order not to allow him to answer the question. 6 That's my position. 7 MR. WAGNER: I understand, and I'll give 8 it some thought when we break. 9 Q Dow Chemical wasinvolvedin making 10 trichlorophenol since approximately 1946, correct? 11 A Yes. 12 Q And was the trichlorophenol, as far as you know, 13 in your time with the company, always made in the 14 199 building? 15 A Yes. 16 Q Not havingbeen to Midland, Michigan, before, can 17 you describe for me, is the 199 building part of a 18 manufacturing complex, or does it stand by itself 19 somewhere? 20 MR. WAGNER: I object to the form, 21 vague. 22 A It's in the midst of a very large manufacturing 23 complex. 2185 P- 27 1 Q And around the 199 building are other buildings 2 where other chemicals or components of chemicals 3 are made? 4 MR. WAGNER: I object to the form of the 5 question. 6 A Yes. 7 Q From atimingstandpoint, do yourecall that the 8 chloracne in the 199 building was first noticed in 9 January or February of 1964? 10 A Yes. 11 MR. WAGNER: Let me object to the form 12 of that as vague. It doesn't identify noticed by 13 whom. 14 Q Was thechloracne mostly due to theexposure to 15 the caustic insoluble oils of the trichlorophenol? 16 MR. WAGNER: I object to the form of the 17 question, calls for conclusion, no predicate for 18 the opinion. 19 A Now I need a repeat. 20 (The requested material was read by the 21 reporter.) 22 A I believe so. 23 Q What are the caustic insoluble oils, is that a 2186 28 1 by-product of the manufacture, if you know? 2 A It's a waste stream. 3 Q A waste? I didn't hear you. 4 A Waste stream. 5 Q Stream, okay. Can you describe for me what the 6 chloracne looked like that you saw? 87 MR. WAGNER: I object as to the breadth, time frame. 9 A Collection of blackheads on the face. 10 Q Did it look something like teenage acne? 11 MR. WAGNER: I object to the form. 12 A Yes. 13 Q Did Dow Chemical knowthat certain chlorinated 14 organic compounds caused chloracne since 1941? 15 MR. WAGNER: I object to the form, 16 imprecise as to Dow and attributing knowledge. 17 A Some people in DowChemical knew that. 18 MR. LUTZ: Would you read that back. 19 (The requested material was read by the 20 reporter.) 21 Q Do you know which certain people at Dow knew that 22 since that time period? 23 A Don D. Irish and others in the biochemical 2187 29 1 research department are the only ones I know for 2 sure. 3 Q Would Dr. Rowe be one of those? 4 A I believe so. 5 Q In 1944 or '45, did Dow first test the caustic 6 insoluble oil portion of the trichlorophenol 7 production to determine whether that was causing 8 chloracne? 9 MR. WAGNER: I object, no predicate as 10 to personal knowledge, calls for speculation 11 otherwise. 12 A I wasn't employed at that time at Dow Chemical. 13 Q You reviewed the history, however, did you not, at 14 some point in time, as to the trichlorophenol and 15 history of chloracne at the company? 16 A Yes, I did. 17 MR. WAGNER: I object, compound, vague. 18 Q And based on your review of the history in 1944 or 19 '45, did Dow Chemical first test the caustic 20 insoluble oil portion of the trichlorophenol 21 production to see if it caused chloracne? 22 MR. WAGNER: I object, no predicate, 23 vague. 2188 D- w s i T 30 1 A I believe so. 2 Q At some point in the 1950s, and then, and this is 3 either based on your personal knowledge or your 4 review of the history of this matter, at Dow 5 Chemical, did a German company propose that there 6 may be a compound, TCDD, responsible for causing 7 chloracne? 8 MR. WAGNER: I object, vague, no 9 personal knowledge. 10 A I believe so. 11 Q And I think that, in your memoranda, when you 12 first got involved with the problem in 1964, you 13 called it by the name TCBD, correct? 14 MR. WAGNER: You mean TCDD? 15 MR. SCHULER: Right. 16 A Yes. 17 THE REPORTER: Wait a minute, is it TCBD 18 or TCDD? 19 Q I'llask thequestion again tomake it clear, in 20 your memoranda, TCDD was called TCBD? 21 A Yes. 22 Q And I'm going to refer to it as TCDDsince we have 23 been referring to it in this case, and in the 2189 d -;u s (c 31 1 scientific literature, apparently those are the 2 initials of preference -- 3 MR. WAGNER: For clarification purposes, 4 you're talking about the 2,3,7,8 isomer? 5 MR. SCHULER: Right. 6 Q Was TCDD the primary culprit in the causation of 7 the chloracne outbreak in 1964 at Dow Chemical 8 Company at the 199 building? 9 MR. WAGNER: I object to the form, calls 10 for opinion, no predicate. 11 A I think so. 12 Q Had you ever been told that TCDD was the most 13 potent chemical ever tested in Dow's toxicology 14 laboratory? 15 A To the best of my recollection, yes. 16 Q Prior to 1964, had the German company, Boehringer 17 Sohn, sent a letter to Dow and other manufacturers 18 of trichlorophenol with suggestions on how to 19 avoid generating the chemical that causes 20 chloracne in the TCP process? 21 MR. WAGNER: I object to the form of the 22 question. 23 A Yes. 2190 O-AAi 7 32 1 Q Do you recall what those suggestions were? 2 MR. WAGNER: Same objection, best 3 evidence rule. 4 A The only one I remember specifically was a 5 temperature limit for the process. 6 Q And what was the suggestion with regard to 7 temperature? 8 MR. WAGNER: Same objection. 9 A I believe it was 150 degrees, but to be honest, I 10 don't remember whether it was F or C, which makes 11 a little difference. 12 Q Do you know, in 1964, whether Dow Chemical, in its 13 manufacture of trichlorophenol, at least to the 14 extent you investigated it, was raising the 15 temperature above 150 degrees Centigrade? 16 A Run that by one more time, please. 17 Q Yes. Do you know in 1964 whether Dow Chemical, in 18 its manufacture of trichlorophenol at the 199 19 building, was raising its temperature in the 20 manufacturing process above 150 degrees 21 Centigrade? 22 A I was told they were, yes. 23 Q Do you know what the temperature was that was i 2191 33 1 being used for the manufacture of trichlorophenol 2 then at that time? 3 A I don't know it with certainty, but I believe it 4 was around 200 degrees. 5 Q Do you know why the temperature for the 6 manufacturing process of TCP was at 200 degrees at 7 that time? 8 A No. 9 Q Who was responsible for making decisions like 10 that, as far as the manufacturing process is 11 concerned? 12 MR. WAGNER: Temperature decisions? 13 MR. SCHULER: Right. 14 A Engineers or plant management, I don't know for 15 sure. 16 Q Do you know who the person who would have been 17 responsible for that decision at that time was? 18 A I don't know with certainty who that would be, no. 19 Q Do you have some names that you recall of people 20 that were involved? 21 MR. WAGNER: I object to the form of the 22 question. 23 A The plant superintendent was Ray Holmes, 2192 o' 34 1 H-O-L-M-E-S, I believe. 2 Q At the 199 building? 3 A Yes. 4 Q Is Mr. Holmes still around, toyour knowledge? 5 A I don't know, to be honestwith you. 6 THE DEPONENT: I'd like to request a 7 two-minute restroom break. 8 Q Let me ask you one more question before you leave, 9 because I want to establish a parameter here, then 10 we'll take a break. At what point chronologically 11 did your responsibilities, if they did, end with 12 regard to chloracne and TCDD and the 13 trichlorophenol process? 14 MR. WAGNER: I object, breadth and 15 vagueness. 16 A I need to hear that one again. 17 (The requested material was read by the 18 reporter.) 19 THE DEPONENT: Did you make your 20 objection? 21 MR. WAGNER: Yes. 22 A Then I can answer. There's no clearcut cutoff 23 time. The way things worked, about 1967 I took on 2193 D-a.2.=)o 35 1 other responsibilities. 2 MR. SCHULER: Okay, let's take a break. 3 (Recess.) 4 BY MR. SCHULER: 5 Q In 1964 was the chemical or the oils that appeared 6 to be causing the chloracne, were they -- was that 7 substance tested on rabbits? 8 MR. WAGNER: I object to the form of the 9 question. 10 Q To your knowledge? 11 A Yes. 12 Q And did it turnout that theconcentration of the 13 chemical causing the chloracne was so high in 1964 14 that the rabbits tested by the rabbit ear test 15 died? 16 MR. WAGNER: I object to the form of the 17 question, vague. 18 A Yes. 19 Q Now, prior toyour being given theindustrial 20 hygiene assignment for the 199 building, among the 21 other responsibilities that you told us you had in 22 connection with the outbreak of chloracne, can you 23 describe for us what the worker safety routine was 2194 p'Z-xHt 36 1 in the plant at the time before you made your 2 recommendations? 3 MR. WAGNER: I object to the form of the 4 question, vague. 5 A Only in general terms and with no certainty 6 because that's been a long time. It would be 7 basically skin protection and the use of gloves 8 when working in areas that may be contaminated, 9 plus personal hygiene instructions on washing 10 thoroughly after any action. 11 Q So gloves were used and then washing. What type 12 of gloves were used, do you recall? 13 A I have no idea. 14 Q Any other safety measures that were in use before 15 you made your recommendations? 16 A I don't remember. 17 Q Were there any type of barriers in the plant 199 18 and the manufacture of TCP? When I say barrier, I 19 mean was it done behind walls or anything like 20 that to protect the workers, or was it an open 21 manufacturing process? 22 MR. WAGNER: I object to the form, 23 vague, over broad. 2195 37 1A 2 It was basically a closed process within vessels and piping and such. 3 Q And were there joints in the pipes, or were there 4 places in which the chemical came out, or was it 5 all enclosed in piping and vessels? 6 MR. WAGNER: I object to the form of the 7 question, compound, vague. 8A I'm not really sure what the question is, here. 9 It was basically closed. There were exits for 10 product and waste streams, and there were joints 11 within the piping, yeah. 12 Q Prior to your prescribing additional measures, did 13 the workers wear any type of protective clothing 14 other than the gloves, other than the normal 15 clothing they might wear? 16 A I honestly don't remember. 17 Q What type of recommendations did you make as far 18 as the worker safety and improving the protection 19 for the workers from the potential for exposure to 20 TCDD? 21 MR. WAGNER: I object, over broad, time 22 frame. 23 A At the time I was safety officer, I required full 2196 O- U93 38 1 company-supplied clothing from the skin, out, 2 required shower time, at least twice a day for 3 lunch break and at the end of the shift, and then 4 respiratory protection at any time there was a 5 risk of airborne material. 6 Q What type of respiratory protection, do you 7 recall? 8 A Two basic forms, depending on the nature of the 9 action the guy was going to take, the cartridge 10 type or air purifying, and in some instances, most 11 of the time it was air supplied self-contained 12 breathing apparatus or air-line respirator. 13 Q What type of company-supplied clothing did you 14 prescribe? 15 A Underwear, shoes, coveralls, gloves. 16 Q The coveralls, were they made from any particular 17 material, if you recall? 18 A Nothing out of the ordinary, no. 19 Q Cotton, if you know? 20 A I don't know. 21 Q Any boots? 22 A Yes, as a matter of fact, I left out that we used 23 a lot of disposal coveralls over the work clothes. 2197 D' 2 7 3 39 1 By disposal, I mean use once and thRowe away, and 2 that included boots that covered their work shoes. 3 Q Did you put the safety recommendations into the 4 form of writing? 5 A I believe so. 6 Q Who was in charge of follow up to make sure that 7 there was compliance with the safety requirements 8 that you outlined? 9 A I was. 10 Q And would you do this by physical observation at 11 the plant, primarily? 12 MR. WAGNER: I object to the form of the 13 question. 14 A I basically lived at the plant, yes. 15 Q Were the workers provided with double lockers? 16 A To my recollection, yes. 17 Q What was the purpose of that? 18 MR. WAGNER: Did you say double lockers? 19 MR. SCHULER: Right. 20 A The purpose was to separate contaminated work 21 clothes from street clothes. 22 Q Were there any special instructions for washing 23 the contaminated clothing or getting rid of it, 2198 40 1 one way or the other? 2 A Yes. 3 Q What were the instructions for that? 4 A To the best of my recollection, we instructed 5 Dow's own laundry, which did the work clothes, in 6 special handling to avoid contact with the 7 contaminated clothing they were laundering. As 8 far as the waste disposal, there was an operating 9 waste disposal department, and I do not recollect 10 -- I do not recall any specific interaction with 11 them, to be honest with you. 12 Q I think you said you recommended two showers a 13 day, is that correct? 14 A During a period of time, yes, I did. 15 Q What period of time? 16 A When I was full-time safety officer in the plant. 17 Q And how would that work, it would be a shower on 18 the way in and a shower on the way out, or how 19 would it work? 20 A No. A shower before the lunch break and then a 21 shower at the end of the shift. 22 Q Were there any special instructions for the 23 showering, other than the normal shower with soap 2199 o azjo. 41 1 and water? 2 A Not that I recall. 3 Q Was the shower and wash time, I think you 4 mentioned this earlier, was that paid time for the 5 employees? 6 A Yes. 7 Q Now, while you were health officer at the 8 particular plant, were there daily safety 9 meetings? 10 A I do not remember specifically. 11 Q How long did you actually serve ashealth officer 12 for the particular plant, 199? 13 A It was a matter of months, six or seven months, I 14 would guess. 15 Q Then after youstoppedserving ashealth officer 16 for the particular plant, what was your next 17 responsibility, if you recall? 18 A No, I don't, to be honest with you. 19 Q The trichlorophenol that wasbeingmanufactured, 20 was that used in the manufacture of 2,4,5-T or 21 Silvex, if you know? 22 A Yes. 23 Q Did you ever serve as health officer for any of 2200 42 1 the plants where the final product was made? 2 MR. WAGNER: Silvex or 2,4,5-T? 3 MR. SCHULER: Yes. 4 A No. 5 Q Are you familiar enough with the chemical process 6 to know or describe for me physically how it was 7 done? In other words, was the trichlorophenol 8 taken in some vat to another building where the 9 2,4,5-T or Silvex was made? 10 MR. WAGNER: I object to the form of the 11 question. 12 A My recollection is it was transported in rail car 13 tanker. 14 Q To anotherbuilding? 15 A Yes. 16 Q Did you ever witness the final manufacturing 17 process where the trichlorophenol and other 18 elements were combined to make the 2,4,5-T or the 19 Silvex? 20 MR. WAGNER: I object to the form of the 21 question. 22 A I don't remember, to be honest with you. I've got 23 to quit saying that. 2201 D ''XZfii 43 1 Q Now, at the time that you first got involved with 2 this process, and the trichlorophenol process and 3 the chloracne outbreak in building 199 in 1964, do 4 you recall what the measurement was for the amount 5 of TCDD in the caustic insoluble oil? 6 A At the time I initially became involved, we didn't 7 know what was in the caustic insoluble oil. 8 Q Do you recall initially -- now, I'm talking about 9 initially when you first got involved -- what the 10 measurement was for the TCDD and the 11 trichlorophenol, the manufactured trichlorophenol? 12 MR. WAGNER: This is not the caustic 13 waste oils, but the TCP, itself? 14 MR. SCHULER: Right. 15 A No. 16 Q At some point were there methods developed for 17 measuring the concentrations of TCDD in the 18 trichlorophenol, for example? 19 A Yes. 20 Q When did that occur, to the best of your 21 recollection? 22 A Early 1965. 23 Q And who developedthose methods, if you recall? i 2202 44 1 A The Dow analytical laboratory in Midland. 2 Q Do you remember specifically who was involved in 3 that project? 4 A Harold Gill, G-I-L-L, was the name I recall. 5 Q Is he still around, to your knowledge? 6 A To my knowledge, yes. 7 Q In Midland or elsewhere? 8 A Last I knew it was Midland. 9 Q Is he retired from the company, do you know? 10 A I think so. 11 Q And was the method that he developed the vapor 12 chromatography or gas chromatography method? 13 A Yes. 14 Q And do you recall, back in 1964 or1965, anything 15 about the measurements that were taken of the 16 finished trichlorophenol as far as the amounts of 17 TCDD that may have been in that particular 18 chemical? 19 A Yes. I'm trying to get a handle on that question. 20 You're asking if I remember any amounts found? 21 Q Yes, if you remember the measurements that were 22 taken, through this gas chromatographic method, of 23 any amounts of TCDD that were in the finished ` 2203 D - 2 2C>O 45 1 trichlorophenol that was produced back at that 2 time? 3 A Yes, generally undetectable, yeah. 4 Q And when you say undetectable, can you describe 5 that a little more fully for me? 6 A Below the limit of detection of the analytical 7 method at that time. 8 Q And what was the sensitivity, if you know, of the 9 analytical method developed back at that time? 10 A Early on, it was as high as ten parts per million 11 of TCDD. 12 Q And then did that improve, later on, to some 13 lesser amount? 14 A Over a period of time, yes. 15 Q And if you recall, over what period of time did 16 the sensitivity improve and to what level did the 17 sensitivity improve? 18 MR. WAGNER: If you have a recollection. 19 I caution you not to guess because there are 20 people that would have that knowledge, but if you 21 know, please give him the information. 22 A Okay. Over some period of time after the 23 development of the method, it improved in stages 2204 0 - % 3o( 46 1 to one per million, one-tenth, .01, I think, part 2 per million. 3 Q Do you know whether the final commercial grade 4 product of 2,4,5-T or Silvex was ever tested 5 through the gas chromatographic method to 6 determine the amount of TCDD that may have carried 7 over in the process to the final product? 8 MR. WAGNER: I object as to the breadth. 9 A That's a mouthful. You're asking if I know 10 whether any of the products were tested by the 11 analytical method? Yes. 12 Q And can you tell me, and you can make it specific 13 to point in time, if you would like, what the 14 results were for the testing of the final product? 15 MR. WAGNER: Same objection as to 16 breadth and vagueness. 17 A Generally non-detectable in products. 18 Q At what point in time, if you recall? 19 A Mid sixties. 20 Q And what was the sensitivity level of the 21 detection equipment? 22 A It improved over time. 23 Q Can you tell me what the level was, if you know, 2205 P-A302- 47 1 at a specific point in time? 2 A It was one part per million at some point in time, 3 yeah. 4 Q Had Dow Chemical determined that there was some 5 safe level of TCDD in its final product that was 6 acceptable to the company? 7 MR. WAGNER: I object to the form, 8 vague, undefined terms, and over broad as to time. 9 A The answer is no. 10 Q Was there ever any manufacture of 2,4,5-T or 11 Silvex that you're aware of, while you were with 12 the company, that was completely devoid of the 13 TCDD contaminant, in other words, a clean product? 14 MR. WAGNER: I object to the form of the 15 question and you cannot detect -- my problem with 16 the form of that is it's impossible to detect the 17 absence of anything in a chemical, so it's 18 unanswerable in its present form. 19 A Give it to me one more time. 20 (The requested material was read by the 21 reporter.) 22 A I have no way of knowing. The answer is I don't 23 know. 2206 V- 9.303 48 1 Q Do you know whether there was testing of the 2 trichlorophenol to determine whether it would 3 carry dioxin, the TCDD dioxin into the final 4 2,4,5-T product? 5 MR. WAGNER: I object to the form of the 6 question, vague. 7 A Yes. 8 Q What was the result of that, what was determined? 9 A Most of the 2,4,5-T contained undetectable amounts 10 of the TCDD. 11 Q Would the same be true for Silvex? 12 A I don't remember. 13 Q What about 2,4-D, was that ever tested, to your 14 knowledge, to determine whether that contained any 15 detectable amounts of TCDD? 16 A I believe it was. 17 Q Do you know what the result of that was at a 18 specific point in time? 19 A No. 20 Q In addition tothe manufacturing process, did you 21 also develop lab safety procedures for handling 22 the dioxinTCDD in the laboratory? 23 A Yes. 2207 P-J304 49 1 Q What type of procedures did you institute at what 2 point in time for that? 3 A My recollection is the late sixties I wrote lab 4 safety procedures that basically instructed 5 employees to avoid all contact and to wash 6 thoroughly after any handling, just in case there 7 was contact. 8 Q Were there any other procedures with regard to the 9 wearing of clothing like gloves or boots or 10 coveralls for the lab people? 11 A Yes. 12 Q What specifically do you recall about that? 13 A Gloves. 14 Q Anything else? 15 A Nothingelse specifically. 16 Q Were the lab people supposed to wear respirators, 17 also, or wasn't that in the recommendation? 18 A I don't believe it was recommended. 19 MR. WAGNER: Just for your timing 20 purposes, Larry has expressed a desire to go to 21 Max and Irma's, which is across the street, so if 22 you could shoot for a break, about five to 12:00, 23 we'll beat the lunch cRowed. 2208 0- 2 3 0 ^ 50 1 Q Have you had any experience with dioxins other 2 than TCDD that caused chloracne at Dow Chemical 3 Company? 4 MR. WAGNER: I object, no predicate. 5 A Not to my knowledge. 6 Q Do you know whether there were dioxins, other than 7 TCDD, which caused chloracne in the 8 trichlorophenol back in 1964? 9 MR. WAGNER: I object, no predicate. 10 A Not to my knowledge. 11 Q What about other compounds, such as furans, that 12 caused chloracne, in the trichlorophenol back in 13 1964? Are you familiar with whether or not there 14 were any of those in the trichlorophenol? 15 MR. WAGNER: Same objection. 16 A Not to my knowledge. 17 Q Do you know, in the finished product of 2,4,5-T or 18 Silvex, whether those finished products, in your 19 experience, were tested for either furans or other 20 dioxins that were chloracnegenic in the sixties? 21 MR. WAGNER: Same objection. 22 A Not to my knowledge. 23 Q What about in the seventies? 2209 D-23ot, 51 1A I don't know. 2 Q Do you know who has that information or knowledge? 3 A No, I don't, to be honest with you. 4 Q Was one of the concerns back in the sixties that 5 TCDD might be a problem for customers using the 6 end product Silvex or 2,4,5-T? 7 MR. WAGNER: I object to the form of the 8 question, over broad as to time, vague as to whom 9 he's making reference. 10 A Yes. 11 Q What specifically was the concern regarding the 12 customers using Silvex or 2,4,5-T end products? 13 MR. WAGNER: Same objection. 14 A The concern, as I recall it, was that customers 15 would not be as careful in protecting employees as 16 was Dow Chemical, less controlled conditions for 17 the employees, in other words. 18 Q After the 1964 chloracne outbreak in the 19 trichlorophenol plant, there was a meeting, I 20 believe, that was called by Dow Chemical and some 21 other chemical manufacturers regarding TCDD, 22 correct? 23 MR. WAGNER: I object to the form of the 2210 V 23o7 52 1 question, and no predicate. 2 A Yes. 3 Q Were any of Dow's customers, in the sense of the 4 chemical companies that Dow sold these products 5 to, Silvex or 2,4,5-T, notified of this problem 6 back in 1964? 7 MR. WAGNER: I object to the form of the 8 question. 9 A The form of your question is -- I think the answer 10 is I don't know. 11 Q Are you aware of any testing that Dow Chemical 12 Company did of any of the end products, 2,4,5-T or 13 Silvex, to determine whether those products were 14 toxic to humans? 15 MR. WAGNER: Contains undefined terms 16 and vague. 17 A I don't know. 18 Q You were not involved in anything like that, 19 correct? 20 A No, I don't believe so. 21 Q You mentioned one part per million contamination 22 level for TCDD. Was that an established level by 23 Dow Chemical Company for Silvex and 2,4,5-T in the 2211 E?.a3otf 53 1 1960s? 2 MR. WAGNER: I object to the form of the 3 question. It mischaracterizes the prior testimony 4 which was in reference to a detection limit. 5 A Not to my knowledge is the answer. 6 Q As far as the one part per million TCDD in Silvex 7 or 2,4,5-T, was this a detection limit for the 8 equipment back then in the 1960s? 9 A At some time, yeah. 10 Q Was there any testing done to determine whether a 11 contamination level of one part per million of 12 TCDD in Silvex or 2,4,5-T was safe to human 13 beings? 14 MR. WAGNER: I object to the form of the 15 question, undefined terms, not enough there to 16 meaningfully answer. 17 A I do not know. 18 Q Do you know what the detection limit was for TCDD 19 in end product 2,4,5-T or Silvex in 1975? 20 A I do not know. 21 Q Do you know who would know that? 22 A No. 23 Q Do you know what division in the company was , 2212 V- 0e! 54 1 responsible for determining that? 2 A Probably agriculturalproducts division. 3 Q Do you know who the head of agricultural products 4 was back in 1975? 5 A No, I don't. 6 Q Did you work with anyone in that division, 7 agricultural products, in the 1974-75 time period? 8 A Not that I recall. 9 Q Would the product quality control people, who had 10 tested the final product, be in that division, 11 agricultural products division, is that what 12 you're saying to me? 13 A I believe so. 14 Q Was the agriculturalproducts division located in 15 Midland in 1974-75, the headquarters of it? 16 A I believe so. 17 Q And we're sitting here today in somebuildings 18 that have DowElanco on the front of it. Do you 19 know the relationship between DowElanco and Dow 20 Chemical Company? 21 A No is a good answer to that. 22 Q Do you know, at some point in time, was there a 23 division of Dow Chemical that was here in 2213 (7-3310 55 1 Indianapolis that was renamed DowElanco, if you 2 know? 3 A I really don't know. 4 MR. WAGNER: He really doesn't know. 5 Off the record. 6 (Discussion held off the record.) 7 MR. SCHULER: Let's go back on the 8 record. 9 Q So I'm clear about this, the testing of the final 10 product Silvex and 2,4,5-T for any contaminants 11 back in 1974 and '75, let's say, would have been 12 done someplace in Midland, Michigan, if you know? 13 A I just have to guess, yes. I wasn't involved. 14 MR. WAGNER: Your role is not to guess. 15 THE DEPONENT: Thank you, sir. I got 16 tired of hearing myself say I don't know. 17 Q Was there, again, going back to '74 and '75, but 18 even earlier, if you know, did Dow have a 19 government affairs division? 20 MR. WAGNER: Over broad as to time. 21 A I don't remember. 22 Q Did you know a fellow by the name of Andrew 23 Anderson? 2214 9.23(1 56 1 A I don't remember. 2 Q Did you know an A.P. Beutel, B-E-U-T-E-L? 3 A I believe so. 4 Q Do you know what Mr. Beutel's role? 5 A My recollection of A.P. Beutel is general manager 6 of the Texas division when I started work at Dow 7 and for many years afterward. 8 Q You mentioned the Texas division earlier. What 9 was the Texas division responsible for, what kind 10 of manufacturing? 11 MR. WAGNER: I object as to breadth, 12 time frame. 13 A Basic industrial chemicals. 14 Q Including agricultural chemicals? 15 A Not to my knowledge. 16 Q If I understand you correctly, you do not know who 17 Andrew Anderson is, correct, you don't recognize 18 the name? 19 A The name is vaguely familiar, but I have no 20 recollection of the gentleman or what he did. 21 Q And Mr. Beutel, you said you remembered for his 22 being the manager of the Texas division at some 23 point in time? 2215 p. a3ia 57 1 A Yes. 2 Q But that's about allyou know abouthim? 3 A That's all I remember about him, yeah. 4 Q Did you know a Dr. Hoerger, H-O-E-R-G-E-R? I'm 5 probably mangling that name, also. 6 A I remember the name, yes. 7 Q Do you know what his role was at Dow Chemical, to 8 your knowledge? 9 A My only recollection of him is as a chemist 10 research scientist. 11 Q Did he have anything to do with 2,4,5-T, Silvex or 12 2,4-D, to your knowledge? 13 A I don't remember him having any involvement. 14 Q Was there a group called the product stewardship 15 group? 16 MR. WAGNER: I object as to the breadth, 17 time frame. 18 A Not in the sixties. 19 Q When did that come about, if you know? 20 A I have no idea. 21 Q Do you recall such a group, or you just don't have 22 any recollection? 23 A I have no recollection. 2216 D. 313 58 1 Q Do you know a Dr. Hinman, H-I-N-M-A-N? 2 A Yeah. 3 Q Who is Dr. Hinman? 4 A For some period of time he was director of the 5 biochemical research lab. 6 Q Do you know approximately what point in time? 7 A No. It would be guessing. 8 Q Sixties or seventies, can you be that specific? 9 A Late sixties. 10 Q Do you know whether he did any research with 11 regard to 2,4-D, 2,4,5-T or Silvex? 12 A I have no knowledge of that at all. 13 Q Was there ever a 2,4-D task force set up within 14 Dow Chemical Company, to your knowledge? 15 A No. 16 Q Did you know a fellow by the nature of Chet Otis, 17 0-T-I-S? 18 A I remember Chet Otis, yes. 19 Q And what was his position at the company? 20 A I don't know his official position in the company. 21 Q Dr. Rowe mentioned in his deposition that at some 22 point in the fifties there was a visit from a 23 fellow from a German chemical company, by the name 2217 0 231*/ 59 1 of Oettel, O-E-T-T-E-L. Do you recall meeting 2 with this gentleman? 3 MR. WAGNER: I object to the form of the 4 question. 5 A No. 6 Q Do you know a J.D. Doedens, D-O-E-D-E-N-S? 7 A I remember the name. 8 Q Do you know what his role with the company? 9 A I remember nothing more about him. 10 Q When you were involved with the trichlorophenol 11 process back in 1964 and sought to determine 12 exposure levels, was the process of doing that the 13 taking of the wipe tests and the air samples, is 14 that how you did it? 15 MR. WAGNER: I object to the form of the 16 question. 17 A Yes. 18 Q Were there any other ways that you determined 19 exposure levels other than that? 20 A Observation. 21 Q Physical observation at the plant, itself? 22 A Yes. 23 Q Do you recall anyspecificrecommendations with 22O1-8 60 1 regard to correcting operating procedures or 2 changing operating procedures as far as the 3 manufacture of trichlorophenol is concerned in '64 4 and '65? 5 MR. WAGNER: I object to the form of the 6 question, as far as operating procedures is 7 undefined and vague. 8 A I can't recall any specifics. 9 Q Who did you primarily deal with in the '64-65 time 10 period in the toxicology department? 11 MR. WAGNER: I object, no predicate. 12 A V.K. Rowe, the director, Dr. Kenneth Olson, 13 toxicologist. 14 Q What about the medical department, who did you 15 deal with primarily there? 16 A Dr. Benjamin Holder. 17 Q And what about in production, who did you deal 18 with primarily there? 19 A That's too broad a question, I'm sorry. 20 Q Specifically with regard to the production of 21 trichlorophenol, who did you deal with? 22 A Ray Holmes, the superintendent, and A1 Lueck, the 23 assistant superintendent. 2219 D'3~3|(c 61 1 Q How do you spell his lastname? 2 A L-U-E-C-K, I believe. 3 Q Did you deal with anyone specifically that was 4 involved in the production of 2,4,5-T, the end 5 product, or Silvex? 6 A Not that I recall. 7 Q Do you know who would have been involved in 8 working on the process to reduce the content of 9 dioxins in the final product after 1964? 10 MR. WAGNER: I object, nopredicate. 11 A No, I really don't. 12 Q Was there a specific file on dioxin at Dow 13 Chemical Company that information was fed into, to 14 your knowledge? 15 MR. WAGNER: I object as to the breadth. 16 A Not to my knowledge. 17 Q Were there specific, to your knowledge, toxicology 18 files on the different chemicals, 2,4-D, Silvex, 19 2,4,5-T? 20 A Y e s . 21 Q And where were those kept, if you know? 22 A In the building wheretoxicology was located, 23 biochemical research department. . 2220 p- 3-311 62 1 Q Prior to today, has your deposition been taken in 2 any other cases involving allegations that either 3 2,4-D or Silvex or 2,4,5-T caused physical injury? 4 A Not to my knowledge. 5 Q And when I say any other cases, I'm talking about 6 any other civil cases, other than that one? 7 A Not to my knowledge, is the answer. 8 Q Was your deposition taken at all in the, for lack 9 of a better term, Agent Orange group of cases? 10 MR. WAGNER: I object to the form of the 11 question. 12 A Yes. 13 Q Once or more than once? 14 A I don't remember. 15 Q Do you recall at what point in time it may have 16 been taken? Was it back in the early eighties or 17 late seventies? 18 A Early eighties. 19 Q And do you recall who may have taken your 20 deposition back then? 21 A No, I do not. 22 Q Was it taken in Midland or some other place? 23 A It was taken in Long Island, somewhere. 2221 D-331S? 63 1 Q Other than that deposition, has your deposition 2 been taken before in context with any claimed 3 allegations of defects in the 2,4-D or 2,4,5-T or 4 Silvex products? 5 MR. WAGNER: I object to the form of the 6 question. 7A I just do not remember. 8 Q Did you know an F.D. Axe, A-X-E? 9 A Yes. 10 Q Was he anindustrialhygienist? 11 A Yes. 12 Q I don't remember him being named in the group that 13 you named earlier, but do you recall when he was 14 with the company? 15 A He's been with the company for a lot of years, 16 mostly in the western division. He spent some 17 time in the industrial hygiene group in Midland. 18 Timing is vague in my memory. 19 Q When you say western division, what are you 20 talking about? 21 A There is a production division at Pittsburg, 22 California, and research lab, also, and Rick was 23 the industrial hygienist out there most of the 2222 p-23i9 64 1 time he was with Dow Chemical. 2 Q Pittsburg, California, is that right? 3 A Yes, with no H. 4 Q Was that division involved in manufacturing either 5 2,4-D or 2,4,5-T or Silvex, to your knowledge? 6 A Not to my knowledge. 7 Q Did you have any input intolabeling of 2,4-D or 8 2,4,5-T or Silvex? 9 A No. 10 Q Do you know who was responsible for that? 11 A No. 12 Q When you would submit your reports regarding 13 contamination of trichlorophenol or the caustic 14 insoluble oil involved in the trichlorophenol 15 process as a by-product, would your reports 16 generally be submitted to the toxicology section, 17 Dr. Rowe and those folks? 18 MR.WAGNER: Iobject as to the breadth. 19 A Yes. 20 Q Would the reports be submitted to any type of 21 governmental affairs section or anything like that 22 at Dow Chemical? 23 MR. WAGNER: Same objection. 2223 O ' 0 3 3 l0 65 1 A I don't remember. 2 Q Do you knowMarguerite Leng,L-E-N-G? 3 A Yes. 4 MR. WAGNER: Did you say Marguerite? 5 Q Marguerite. Who isMarguerite Leng? 6 A She was a scientist. My recollection of her was 7 as a member of the toxicology lab for some period 8 of time. Vague recollection that she spent some 9 time in agricultural research department at Dow in 10 Midland. 11 Q Do you know what her role was with either the 12 toxicology lab or agricultural research? 13 A I really do not remember. 14 Q Did Dow, if you know, have any specific department 15 or division or group of people that were involved 16 with the registration of agricultural pesticides? 17 MR. WAGNER: I object as to the breadth, 18 time period. 19 A I was aware that they did, yeah. 20 Q Did you ever deal with any of those folks 21 yourself? 22 A Not that I remember. 23 Q Do you know who the head of that department was or 2224 66 1 anybody in that department? 2 MR. WAGNER: Same objection. 3 A No. 4 Q Do you know whether Marguerite Leng has anything 5 to do with that? 6 A She may have, but I don't know for sure. 7 MR. SCHULER: You want to take a break? 8 It's five to 12:00. 9 MR. WAGNER: Sure. 10 (Recess.) 11 MR. SCHULER: Back on the record. 12 Q Mr. Silverstein, let me ask you initially, as we 13 begin this afternoon, did you review anything 14 before your deposition here today of a documentary 15 nature? 16 MR. WAGNER: That's a yes or a no. 17 A Yes. 18 Q What did you review, sir? 19 MR. WAGNER: To the extent you reviewed 20 things with me, I instruct the witness not to 21 answer. If you reviewed things on your own, feel 22 free to tell him. 23 MR. SCHULER: If you reviewed documents 2225 67 1 of the company, I think it's included. Just 2 because you handed them to him -- 3 MR. WAGNER: His discussions or 4 preparations with me before this deposition, the 5 substance of that is work product. 6 MR. SCHULER: I'm not asking for 7 discussions. I'm asking if he reviewed documents. 8 MR. WAGNER: It's work product. 9 Q What have you reviewed, sir? 10 MR. WAGNER: I'll instruct you not to 11 answer. 12 MR. SCHULER: All right, we'll be back 13 on that one, I'll guarantee you that. 14 Q Have you reviewed any depositions, sir? 15 A No. 16 Q Have youreviewed anyDowChemicalCompany 17 documents? 18 A Yes. 19 Q What have youreviewed that are Dow Chemical 20 Company documents? 21 MR. WAGNER: Same instruction. 22 Q I want to be clear for the purpose of the record, 23 so when we come back at your expense, that I'm not 2226 Q .03*3 68 1 asking if you have reviewed anything prepared by 2 any attorneys of any shape or form whatsoever. 3 I'm asking you if you reviewed any Dow Chemical 4 Company documents, not prepared by any lawyers? 5 MR. WAGNER: Same instruction. 6 Q Have you reviewed anything else in preparation for 7 your deposition here today, sir? 8 MR. WAGNER: To the extent that you 9 reviewed things with me, I instruct the witness 10 not to answer. If you did things apart from me -11 A No, I haven't. 12 Q So your testimony here today is that you haven't 13 reviewed any documents that were not handed to you 14 by a lawyer, I guess, is that fair enough? 15 MR. WAGNER: You can answer that. 16 A Yes. 17 Q Let me ask you if you have spoken with anybody 18 other than the attorneys, regarding preparation 19 for your deposition here today? 20 A No. 21 Q Have you ever testified before the Environmental 22 Protection Agency or any of its subcommittees? 23 A No. 2227 D 3-3SW 69 1 Q Since leaving Dow in 1979, I believe you said, is 2 that correct? 3 A That's correct. 4 Q Do you maintain, either personally or through your 5 company, any consulting arrangements with Dow? 6 A No, sir. 7 Q When I say Dow, I mean any of its divisions like 8 DowElanco or any subsidiaries or anything of that 9 nature? 10 A No. 11 Q Do you maintain contact, and when I say maintain 12 contact with, either on a professional or personal 13 level, with anyone you worked with at the company, 14 Dow? 15 A Yes. 16 Q Who particularly do you maintain contact with? 17 A Primarily in the industrial hygiene and toxicology 18 areas, a number of folks. 19 Q And give me the names of three or four of those. 20 A Dr. Larry Rampy, Gordon Ingdol. 21 Q Who is Dr. Rampy? 22 A He was, at the time, the director of industrial 23 hygiene, Dow Chemical U.S.A., I believe. 2228 D'23^ 70 1 Q And during what years did he hold that position? 2 I gather from what you're saying he doesn't hold 3 it anymore? 4 A No. He recently got a new job that I don't know 5 about, but I don't know, '75 to '90 or '91, or 6 '92, somewhere in that range. 7 Q Where is he working now? 8 A He's still at Dow, but I don't know his new 9 position. 10 Q Still in Midland? 11 A As far as I know. 12 Q And Rampy, R-A-M-P-E? 13 A R-A-M-P-Y. 14 Q What other folks do you still maintain contact 15 with? 16 A Bruce Houhman, manager of industrial hygiene for 17 DowElanco. Greg Socha is radiation safety officer 18 here. They're friends from Midland. 19 Q How do you spell the last name? 20 A S-O-C-H-A. 21 Q Any others? 22 A Patty Houhman, worked for me at Dow Corning when I 23 was manager. 2229 Q.p-3<2t> 71 1 Q How do you spell her name? 2A I think it's officially Patricia, H-O-U-H-M-A-N. 3 Q What was her position when she was working with 4 you? 5A She was an industrial hygienist at Dow Corning. 6 Q Is she still there? 7 A No. 8 Q Where is she located now? 9 A Physically here in the Indianapolis area. 10 Q Is she with another company? 11 A No. 12 Q Still with Dow? 13 A She doesn't work full time to my knowledge. 14 Q She doesn't work with Dow any longer or part time 15 or -- 16 A Last I knew she was part time with Dow Corning, 17 industrial hygiene. 18 Q In 1964, when you were called in to help evaluate 19 the chloracne problem in the trichlorophenol 20 process, and in the course of your involvement 21 with that, did you ever communicate to any 22 governmental agencies the fact that there was a 23 substance in the trichlorophenol process that was 2230 72 1 causing chloracne in Dow workers? 2 A No. 3 MR. WAGNER: I object as to the 4 predicate. 5 Q Did you ever communicate that fact to any 6 scientific organizations? 7 MR. WAGNER: I object on the predicate. 8 A Not that I remember. 9 Q Did you ever communicate that fact publicly 10 outside the company in any way? 11 A Not that I remember. 12 Q Do you know if there were any claims by workers, 13 as a result of the 1964 chloracne outbreak, 14 against Dow? 15 A No. 16 Q You don't know one way or the other? 17 A I don't know one way or the other. 18 Q Have you ever testified in any case or proceeding 19 involving any claim by any worker who got 20 chloracne as a result of working at Dow, whether 21 it was 1964 or any other time? 22 A No. 23 Q I asked you earlier if you testified in any civil 2231 73 1 cases where there were allegations of personal 2 injury from exposure to a Dow product. Have you 3 testified in any cases whatsoever, civil cases, 4 where Dow Chemical Company was a defendant? 5 A No. 6 Q Let me show you some documents that I have here, 7 and most of these, if not all of them, were marked 8 as exhibits to the deposition of Dr. Rowe. This 9 particular one happens to be Deposition Exhibit 10 10 to that deposition, and I'll ask you, first of 11 all, if you can identify that particular document? 12 A To the extent that it is, you know, entitled, and 13 obviously I wrote it, yes, I can identify it. 14 Q What is the document? Just give me a general 15 identification for the purpose of the record. 16 A It is a description of the part played by my 17 department, the biochemical research department, 18 in Dow's chloracne problem. 19 MR. SCHULER: And we'll just go ahead 20 and mark that as Exhibit 1 to this deposition. 21 MR. LUTZ: What exhibit was it to Rowe's 22 deposition? 23 MR. SCHULER: 1 0 . 2232 D- P3SL? 74 1 (Plaintiff's Exhibit 1 was marked for 2 identification.) 3 Q Looking at Plaintiff's Exhibit 1, it's entitled 4 the Chloracne Problem, Biochem's Contribution. 5 Who asked you to prepare this document, do you 6 recall, Mr. Silverstein? 7 A I don't recall specifically. 8 Q At the top, in handwritten letters, it says 9 Mr. Lynn, and then there's some handwriting that 10 says early history of -- early Dow history of, is 11 that your handwriting? 12 A This, I don't think is. I'm pretty sure that 13 isn't, and I know that isn't. That and the date 14 look like my handwriting. 15 Q Do you know whose handwriting this would be at the 16 top that's not yours? 17 A I don't recognize that, no. 18 Q In the first paragraph of Plaintiff's Exhibit 1, 19 you make the comment there's evidence that other 20 compounds, than the one already isolated and 21 identified and studied, are capable of producing 22 trichlorophenol, and I've highlighted those words 23 there. Can you tell me what other compounds you 2233 D' 75 1 were referring to? 2 A At that time there was nonspecific analytical 3 evidence that there was a whole series of things 4 in that waste oil, and those are the other 5 compounds I would be referring to. 6 Q But they were not specifically identified at that 7 point in time, is that what you're saying? 8 A At that point in time, this is March 11th, '65. 9 Q I'm looking at page 2 of Plaintiff's Exhibit 1, 10 and the second full paragraph, and I'll show this 11 to you, I only have one copy, but it says, this 12 compound, referring to what appears to be the 13 TCDD, do you see that? 14 A Yes. 15 Q And others, which have been shown to cause 16 chloracne, have also been shown by animal tests 17 and some human experience in other companies to 18 produce liver damage if the exposure is more 19 extensive. Again, do you know what those other 20 compounds are? Can you identify them at this 21 point in time? 22 A They would be the families that I was then aware 23 of that had caused chloracne in humans, such as in 2234 P -5-331 76 1 the thirties, the chlorinated naphthalenes, and 2 earlier Dow experience, before I came there, with 3 materials they suspected, you know, of being the 4 culprits, the chlorinated furans and that type of 5 thing, yes. 6 Q But you're not referring there to other compounds 7 in the trichlorophenol waste oil? 8A I don't remember if that was meant to do that or 9 not, to be honest with you. 10 Q You refer in the last sentence to some European 11 experience with chloracne. Can you tell me who 12 you're referring to there? 13 A Well, there were, as I remember, three big 14 companies in Europe that had had accidents in 15 their plant that had caused some employees to have 16 the chloracne and also some liver damage in other, 17 you know, some of their employees. That's about 18 all I remember of it. 19 Q Do you remember the names of the companies? 20 A The one was Boehringer Chemical in Germany. I do 21 not remember the one in the Netherlands, and I 22 don't remember the one in France, either. 23 Q You mention on page 3, and I'll show you this 2235 P-5,33A 77 1 section of Plaintiff's Exhibit 1, that 2 folliculitis in rabbits appears to be produced, 3 regardless of the severity of exposure. Do you 4 see that there? 5 A Yes, this part that you'vehighlighted? 6 Q Yes. 7 A All right, let me read the whole sentence here. 8 Q Go ahead. 9 A Yes, okay. 10 Q Do you recall where you got that information from? 11 A It had to befromtoxicology, our toxicology 12 department. 13 MR. WAGNER: For purposes of the record, 14 if this is ever offered at trial, this document, I 15 want to object to the highlighting of it and would 16 want a clean copy submitted, as opposed -- 17 MR. SCHULER: You'll certainly get a 18 clean copy. 19 Q In the next sentence.you indicate there's evidence 20 that unknowns, it looks like acnegens, may produce 21 folliculitis in rabbits with a shorter induction 22 period. Can you tell me what you are referring to 23 there? 2236 0-7,335 78 1 A I have no idea what that refers to. 2 Q Are you referring to -3 A I don't recall. 4 Q I didn't mean to cut you off. Are you referring 5 to the contents or contaminants of the 6 trichlorophenol waste oil? 7 A I just don't know whether I was or not. 8 Q I'm looking at the last paragraph on page 3 of 9 Plaintiff's Exhibit 1, where you're talking about, 10 you start off talking about some 1944 research, 11 and I can't make out the last sentence, the word 12 that was inserted there. It says the something 13 product was shown to be inactive by animal tests. 14 Do you know what that says, can you make that out 15 for me? 16 A The handwritten insertion appears to be the word 17 phenate. 18 Q Is that your writing or was that someone else's? 19 A I can't tell. It's too indistinct. 20 Q Can you make out the handwritten scratches that 21 are crossed out at the bottom, or at least tell me 22 if that's your writing? 23 A I can't make out what it says, except for the last 2237 D-333^ 79 1 word which is obviously experience, and it is not 2 my writing. 3 Q Do you know whose writing it is? 4 A No. I don't recognize that writing. 5 Q You mention at the top of page 4 in Plaintiff's 6 Exhibit 1, that in 1955 a number of German 7 manufacturers of trichlorophenol and at least one 8 French company had human experience with chloracne 9 that caused them to shut down production plants 10 and to study the problem. Are those the same 11 companies you referred to earlier, Boehringer, and 12 you couldn't remember the names of the other two? 13 A I believe so. 14 Q On page 4 of Plaintiff's Exhibit 1, you talk about 15 something that happened in 1957 historically in 16 the 199 and 349 buildings, that there were process 17 samples tested on animals, and the caustic 18 insoluble oil and coil reactor product in 199 were 19 active and that tar from color stills in 349 was 20 also active. 21 Are you referring to rabbit testing 22 there? 23 A Yes. 2238 >. 9335" I 80 1 Q And when you say active, are you referring to 2 causing chloracne? 3 A No. 4 Q What are you referring to? 5 A To cause folliculitis in theanimal, or the rabbit 6 ear, and there's a technical difference between 7 that and chloracne. 8 Q Whatis the difference betweenfolliculitis and 9 chloracne? 10 A I'm not a medical person, so I really just as soon 11 not give you an answer, if that's all right. 12 Q If you can't answer it, if you don't feel 13 qualified to answer something, tell me that you 14 don't feel qualified to answer that. 15 A I think that's a good answer, I don't feel 16 qualified. 17 Q You mention in the next sentence, page 4 of 18 Plaintiff's Exhibit 1, that over the years some 19 samples of end products, such as Silvex, and I 20 can't make out the next name, it's handwritten 21 over, can you make out the next one? 22 A Where are we? 23 Q That last highlighted sentence. 2239 p .9 3 3 fc 81 1 A Over the years? 2 Q Right. 3 MR. WAGNER: Are you asking what that 4 word is? 5 MR. SCHULER: Yes. 6 A Looks like Ronnel, R-O-N-N-E-L. 7 Q What is Ronnel, do you know? 8 A It's a agricultural product, but I could not give 9 you the chemical components, okay? 10 Q Okay. You mention that Ronnel, Silvex and 2,4,5-T 11 had been tested on animals and in no case was 12 chloracne activity detected in these products. 13 Where did you get that information? 14 A Probably from toxicology. 15 Q At Dow Chemical Company? 16 A Yes. 17 Q In the next sentence you mention in 1962 there was 18 additional testing of samples from the then 19 existing process from the pilot run with a 20 decrease in the caustic concentration, and to 21 follow on the next page, those samples were tested 22 in animals and that certain insoluble oil was 23 found to be active. Are you referring to causing 2240 V- A33'7 82 1 chloracne there or some other problem? 2 A I'm referring to causing folliculitis in the 3 animal tests, specifically. 4 Q The next paragraph, then, in your history you 5 refer to the outbreak that occurred in 1964 of 6 chloracne and that the two samples of the oil that 7 were tested were dramatically different than those 8 tested before. Let me show you that and ask you 9 what you mean by that? 10 MR. WAGNER: I object to the form. 11 A Well, as it says, the samples killed the rabbits 12 in the test, in contrast to earlier tests where 13 the rabbits did not die. 14 Q You're referring to the strength of the 15 contaminant there? 16 MR. WAGNER: I object to the form of the 17 question. 18 A Simply the end result. 19 Q Okay, the fact that the rabbits died? 20 A Yes. 21 Q And you subsequently refer, in the next couple of 22 sentences that I'll show you on page 5 of 23 Plaintiff's Exhibit 1, that the concentration of 2241 V' 3.33^ 83 1 the caustic insoluble oils had to be diluted from 2 the usual 10 percent to .1 percent concentration 3 before the animals survived, do you see that? 4 A Yes. 5 Q Where did you get thatinformation from? 6 A Toxicology. 7 Q Do you know who was conducting these tests at this 8 time in 1964? 9 A To the best of my knowledge, it was Dr. Kenneth 10 Olson. 11 Q He was a toxicologist with thecompany at that 12 time? 13 A Yes. 14 Q You mention at thebottom of thefirst full 15 paragraph on page 5 of Plaintiff's Exhibit 1 that 16 the tests had been repeated periodically, to the 17 extent that over 600 animal tests directly related 18 to the chloracne problem had been run since July, 19 and there's a date that's cut off there. Do you 20 see that last sentence? 21 A Yes, I see it. 22 Q Was that information yougot fromtoxicology, 23 also? 2242 0- 3 3 - ^ 84 1 A Yes. 2 Q And would that have been Dr. Olson, as well, that 3 was doing that testing? 4 MR. WAGNER: I object, the predicate. 5 Q The circle around the sentence with the insertion 6 of the phrase in that particular sentence, is that 7 something that you did, or did somebody else edit 8 this ? 9 A I-- 10 MR. WAGNER: I object to the form of the 11 question. 12 A I honestly don't remember. 13 Q There is a reference in the last paragraph to a 14 Mr. Skelly. Was he one of the toxicologists in 15 the analytical lab? 16 A No. 17 Q What was Mr. Skelly? 18 A Analytical chemist. 19 Q And what division or department was he in? 20 A Analyticallaboratories. 21 Q Is that part of the biochemical research lab? 22 A No. 23 Q Separate? 2243 J 85 1 A Yes, separate. 2 Q You mention in that same sentence that Skelly 3 isolated a number of fractions and among them was 4 the TCDD. Was he the first one in the company to 5 identify that by-product? 6 A May I see the reference? 7 Q Sure. 8 A Your question again, please? 9 Q Was Mr. Skelly the first one at Dow Chemical to 10 isolate the TCDD, to your knowledge? 11 A I don't know the answer. 12 Q Again, there's some editing of the last paragraph. 13 Do you know if that was yours or someone else's? 14 A That doesn't look like my handwriting. I don't 15 know whose it is. 16 Q In the next sentence you refer to two materials 17 that were identical from infrared melting point 18 analysis. Do you know what you're referring to 19 there? 20 A I don't know what that refers to. 21 Q Was Harold Gill in the analytical laboratory also? 22 A Y e s . 23 Q Was he the head of it? 0 - ^ 3 HI 86 1 A Not to my knowledge. 2 Q You mention on page 6 of Plaintiff's Exhibit 1 3 that the vapor phase chromatography, I guess it 4 was called, sensitivity at that time was 5 sensitive, could detect samples -- I guess of the 6 TCDD, down to one part per million by weight, do 7 you see that there? 8 A Yes. 9 Q And there is a subsequent statementthat the 10 rabbits are sensitive to the TCDD down to 11 approximately five parts per billion by weight, do 12 you see that next sentence there? 13 A Yes. 14 Q Where did you get that information, from 15 toxicology also? 16 A The part relating to the rabbits from toxicology, 17 and the other from analytical. 18 Q With respect to those two measurements, if the 19 machines were only sensitive to a measurement of 20 one part per million, how could it be detected, 21 and again, if you're not qualified or can't tell 22 me how they arrived at this, but how could you 23 arrive at the conclusion that the rabbits were 2245 D-Z'bHS- 87 1 sensitive down to five parts per billion? 2 THE DEPONENT: Okay to answer? 3 MR. WAGNER: Sure. 4 A Because the analytical samples, process samples 5 had lots of interferences. Starting with pure 6 material we could accurately dilute down to five 7 parts per billion and test on the animals, so 8 that's what what we did. 9 Q So you took the pure and diluted the pure to five 10 parts per billion? You worked up instead of down, 11 if you will? 12 A I don't remember which way we went. 13 Q Who would have done that research, do you know? 14 A Probably toxicology -- well, I know it was. 15 Q Would that have been Dr. Olson again? 16 A To the best of my recollection, yes, Dr. Olson. 17 Q There's a lot of editing that went on on page 6 18 here of Plaintiff's Exhibit 1. Again, do you know 19 whether you did that or that was somebody else? 20 A Just about impossible to tell, but I don't think I 21 did it. 22 Q And you don't know who did, correct? 23 A No. I can't recognize that handwriting. 2246 "7---- 88 1 Q Referring to the last highlighted sentence here on 2 page 6 of Plaintiff's Exhibit 1, you make the 3 comment that wipe samples with no detectable TCDD 4 but varying amounts of unknowns have shown more 5 activity on the animals than can be accounted for 6 by the low level of TCDD which may be present. 7 Can you tell me where you got that information? 8 THE DEPONENT: Okay? 9 MR. WAGNER: Okay. 10 A My wipe test samples were tested on the rabbit ear 11 because of its great sensitivity. At the same 12 time we had them analyzed by the analytical lab 13 for the materials they could find on it, and that 14 statement arose because wipe samples that showed 15 very little or no TCDD by analytical analysis did 16 produce an effect on the animals. 17 Q And so, I'm not sure I understood you, in other 18 words, the wipe samples were analyzed chemically 19 and then they were also tested on the rabbits? 20 A Yes. 21 Q And in the chemical analysis, even if there was no 22 TCDD collected, they might still be bio-reactive 23 on the animals, is that what you are saying? 2247 D - a 3*// 89 1 A That's correct. 2 Q And the chemical analysis was done with the vapor 3 phase chromatography? 4 A Yes. 5 Q At that time down to a sensitivity of one part per 6 million measurement? 7 MR. WAGNER: I object, no predicate. 8 A To the best of my recollection. 9 Q There's a sentence scratched out at the end that 10 talks about the chlorinated dibenzofurans were 11 tested on animals many years ago and shown to be 12 quite active. Do you recall where that 13 information came from? 14 MR. WAGNER: I object to the form of the 15 question. 16 A Somewhere in the files. 17 Q Toxicology again? 18 A Yes. 19 Q And in the next sentence that was scratched out, 20 it says research was abandoned on these products 21 because of their high acnegenic reactivity. Do 22 you recall what products you were referring to 23 there? 2248 D- 2 ^ 90 1 A No, I don't. 2 Q There's a handwritten page 6, is that in your 3 handwriting? 4 A That appears to be my handwriting. 5 Q That highlighted sentence, could you read into the 6 record for me? 7 A Peaks coincided with some unknowns which were seen 8 in wipe samples and process samples. Both the 9 biochem lab and the Germans have reported animal 10 tests with these compounds which showed acnegenic 11 activity. 12 Q What compounds are you referring to there? 13 A Well, let me see, I think it goes back to the 14 impure chlorinated dibenzofurans that I didn't 15 read. I just read the highlighted. 16 THE DEPONENT: Can I take a break? 17 MR. SCHULER: Sure. 18 (Recess.) 19 BY MR. SCHULER: 20 Q Let me show you page 7 of Plaintiff's Exhibit 1, 21 and I'll ask you to read that first highlighted 22 portion there. 23 A The analytical laboratory and the toxicology 2249 91 1 laboratory are presently conducting a project to 2 determine the analytical and animal test limits of 3 sensitivity for TCBD in various Dow products, I 4 think the word is made, M-A-D-E, from 5 trichlorophenol. This project is aimed at 6 developing a quality control specification for 7 TCBD in consumer products. 8 Q Do you know who was incharge of that project? 9 A No. 10 Q Do you know what standard was ultimately 11 developed? 12 A During the time I was involved, our standard was 13 nothing detectable in the material. 14 Q And I think in one of these other documents we'll 15 get to the various measurements, but in the period 16 of the 1960s, up until 1969, what was the limit of 17 detection, if you know? 1.8 A I don't remember. 19 Q You have a section here in Plaintiff's Exhibit 1, 20 starting at page 7, that deals with the 199 21 building and talks about an animal test that was 22 done, conducted in 1945, which showed the caustic 23 insoluble oil to be active. Do you know what 2250 V-SA'ift 92 1 precautions were recommended back at that time? I 2 know that was before you were with the company, 3 but you referred to precautions. 4 A I don't remember specifically. 5 Q What about 1957, do you know what precautions were 6 recommended at that time? 7 A I do not remember specifics. 8 Q On page 8 of Plaintiff's Exhibit 1, you refer to 9 the Boehringer Sohn Company in Germany asking for 10 information from a Givaudan, G-I-V-A-U-D-A-N, 11 Corporation. Do you know where that company was 12 located and whether or not Dow Chemical had an 13 interest in it? 14 A I have no recollection of that company, Givaudan. 15 Q You mention in the next sentence on page 8 that a 16 letter describing the hazards and precautions for 17 safe handling of 2,4,5-Trichlorophenol was sent to 18 Boehringer with a data sheet from biochem. Did 19 you author that letter? 20 A No. 21 Q Do you know whodid? 22 A No. 23 Q It mentions that the letter answered seven 2251 P-234# 93 1 specific questions regarding our own plant 2 experience. Do you recall what those questions 3 were? 4 A I do not. 5 Q On page 9 of Plaintiff's Exhibit 1, you refer to a 6 January 1964 first medical report of a case of 7 chloracne, initiated a survey by the environmental 8 research laboratory. Do you know who was involved 9 in doing that survey? 10 A That was my assignment to the plant being referred 11 to there. 12 Q And that was, I forget the fellow's name, who was 13 your boss? 14 A Harold Hoyle. 15 Q Hoyle, okay. And where you refer to the 16 operator's job being studied closely and a report 17 being issued on February 5th, 1964, recommending 18 changes in the procedure and the personal hygiene 19 habits, that was your report? 20 A I presume so. 21 Q You mention a company by the name of Phoenix 22 Sprinkler as the company that came in to change 23 some of the equipment on the 199 building. Was 2252 94 1 that a company separate from Dow Chemical, a 2 subcontractor? 3 A To my knowledge, yes. 4 Q And you mention that apparently some of their 5 workers developed chloracne in the process of 6 changing some of this equipment. Do you recall 7 how many? 8 A No, I don't. 9 Q Did you ever meet those men that developed 10 chloracne that were employed by Phoenix Sprinkler? 11 A Not to my knowledge. 12 Q How did you find out about that? 13 A I was told by someone. 14 Q At your company, Dow Chemical? 15 A I would guess so, yeah. 16 MR. WAGNER: Don't guess. 17 THE DEPONENT: You are right. 18 MR. LUTZ: Does that mean you are 19 changing your last answer to you don't recall? 20 THE DEPONENT: I'll change my last 21 answer to I don't recall. 22 MR. LUTZ: I had to say something. 23 Q You mention at the top of page 10 of Plaintiff's , 2253 <D-a35& 95 1 Exhibit 1 that very stringent safety precautions 2 were instituted at the 199 building. Those were 3 the ones we discussed earlier in your deposition 4 here? 5 A Yes. 6 Q You say these include a full-time health 7 supervisor. Do you recall who that was? 8 A Yes. 9 Q Who? 10 A Myself. 11 Q Was there anyone that followed you in that 12 position? 13 A Yes. 14 Q Who? 15 A I don'trecall thename. 16 Q Was that afull-time position after you left it, 17 that was permanently maintained at that building? 18 A No. 19 Q How many followed you, oneother person or more, 20 if you remember? 21 A I don't remember. 22 Q The closures thatyou refer toon page 10 that 23 were put up around parts of the process and that , 2254 96 1 you refer to being put up in November and December 2 of 1964, what type of closures were they, do you 3 recall? 4 A It was basically a very large, metal, rectangular 5 structure around the main process equipment. 6 Q Kind of a wall that was put uparound it? 7 A A wall, yeah. 8 Q Was it completelyself-contained, did it 9 completely enclose the process equipment, or was 10 it open at some point? 11 A It was a closure, as I stated, enclosing the 12 process, yes. 13 Q Was it completed enclosed, or was it open at the 14 top or one of the sides? 15 A It was open only to let pipes and such things 16 through it, yeah. 17 Q Do you remember what material it was made out of? 18 A No. 19 Q On page 11 there's some comment and criticisms, I 20 guess, of the language here. Do you recall who 21 may have written that? 22 MR. WAGNER: I object to the form of the 23 question. 2255 P *2 3 S* 97 1 Q Either the insertions up here or the word out 2 here, that says poor? 3 MR. WAGNER: Same objection. 4 A I don't know who critiqued or edited it, no. 5 Q The 349 building that you refer to on page 11 of 6 Plaintiff's Exhibit 1, you talk about contaminated 7 phenate being processed in that building. Is that 8 a chemical which is a component of any of the 9 herbicides 2,4-D, 2,4,5-T or Silvex? 10 MR. WAGNER: Phenate? 11 MR. SCHULER: Phenate. 12 A Can I see the reference? 13 Q The last -- 14 A Oh, the one that was poor, uh-huh. I'm really not 15 sure is the answer. 16 Q You refer to a building superintendent at 349 by 17 the name of Clare Bailey. Is that a man or a 18 woman, if you know? 19 A It was a man. 20 Q Is he still employed by Dow? 21 A I don't know. 22 Q You mention at the top of page 12 of Plaintiff's 23 Exhibit 1 that there were objections by workmen to 2256 > a 3 5 3 98 1 working in 349, which caused the adoption of 2 full-scale protective measures in that building in 3 regard to the trichlorophenol process. Were any 4 of those objections in written form, if you 5 recall? 6 A I do not recall. 7 Q Do you remember the names of any people who would 8 have objected, any of the workmen? 9 A I wouldn't know any names of the folks. 10 Q You mention in paragraph two of page 12 of 11 Plaintiff's Exhibit 1 that a health supervisor is 12 now stationed at the 349 building. Do you recall 13 who that was? 14 A No, I don't. 15 Q At the top of page 13 in the first full paragraph 16 you discussed Dowicide 3. Do you know what the 17 components were of that particular chemical? 18 A No, I don't. 19 Q In the 267 building, on page 13 of Plaintiff's 20 Exhibit 1, you mention that that is the building 21 where the trichlorophenol from 349 is processed to 22 2,4,5-T acid and 2,4,5-T esters, and you mention 23 that in 1965, samples taken from that building 2257 V- \ 99 1 showed no activity with one exception, and that is 2 the residue from the sodium salt filter press 3 showed slight activity on the rabbit ear. Do you 4 know what activity was shown on the rabbit ear 5 that you're referring to there? 6 A Where the heck are we here? 7 Q Here. 8 A That's not what -- 9 Q Right here, I'm sorry. 10 A That's the folliculitis activity. 11 Q You distributed this March 10th, 1965, memorandum 12 that we marked as Plaintiff's Exhibit 1. There is 13 a handwritten statement at the end that says unit 14 index. Can you tell me what that is? 15 MR. WAGNER: I object to the form of the 16 question. 17 A That was an indexing method used in the lab, 18 meaning write out, you know, the key word so that 19 it could be retrieved, presumably. 20 Q For filing purposes? 21 A Filing purposes, strictly. 22 Q Was there computerization of these things back in 23 1965, or was it manual? 2258 100 1 MR. WAGNER: I object to the form of the 2 question. 3 A I don't remember. 4 Q Can you tell me who these people are at the end in 5 the chain of distribution? 6 MR. WAGNER: I object to the form of the 7 question. 8 Q Is that your handwriting, first of all? 9 A I don't think that's my handwriting. 10 Q Can you read the names there that are listed? 11 A Under distribution is Hutchenreuther. 12 Q And where was he located at the time? 13 A He was a manager in the Midland plant at the time. 14 Goergea, same as Hutchenreuther, G-O-E-R-G-E-A; 15 Staehling, S-T-A-E-H-L-I-N-G, another major 16 manager. I can't read -- oh, Amstutz, 17 A-M-S-T-U-T-Z; J. Kelly, parentheses, W, period, 18 disposal; Shannon, ditto marks under disposal, and 19 Leuck, L-U-E-C-K; Bailey, B-A-I-L-E-Y, and 20 Sculati, S-C-U-L-A-T-I. 21 Q It mentions a J. Kelly. It says something 22 disposal. Who is that individual? 23 A I don't remember Mr. Kelly. 2259 ), P.3'3 t 101 1 Q And Mr. Staehling, where is he located? 2 A He was manager in the Midland plant at that time. 3 Q Mr. Leuck? 4 A He was assistant superintendent at 199 building at 5 the time. 6 Q And I think Bailey we have covered. And the last 7 name -8 A Sculati. 9 Q What was his position? 10 A He was plant superintendent, but I don't remember 11 where. 12 Q At one of the buildings? 13 A Yeah. 14 Q Let me show you this document and ask you if you 15 can identify that? 16 A Y e s . 17 Q What is it, first of all? 18 A It is the, a report of a meeting held at the 19 biochemical research laboratory. 20 Q What is the date? 21 A Memo is dated March29th, 1965. 22 MR. SCHULER: We'll mark that as Exhibit 23 2 . V2- 280 102 1 (Plaintiff's Exhibit 2 was marked for 2 identification.) 3 Q Plaintiff's Exhibit 2 is a report authored by you, 4 Mr. Silverstein? 5 A If you referring to the document we just looked 6 at, yes. 7 Q And what was the purpose of this report, 8 Plaintiff's Exhibit 2? 9A To document a meeting that was held at the 10 biochemical research laboratory on the date 11 indicated. 12 Q There is some handwriting at the top, it says copy 13 to a Bill something or other, I can't make out the 14 name. Is that your handwriting? 15 A No, it isn't. 16 Q Do you recognize the name, can you make it out? 17 A Yes, Bill Haberstoh. 18 Q Better spell that one. 19 A H-A-B-E-R-S-T-O-H. That appears to be V.K.R., 20 V.K. Rowe. 21 Q Who is Mr. Haberstoh? 22 A I don't remember. 23 Q You were present at that meeting of the various 2261 O- 103 1 representatives of the chemical companies, 2 correct? 3 A Yes. 4 Q And you mention in your report that Mr. Rowe 5 referred to evidence for unknown acnegens, and you 6 can take a look at that, if you want. Again, I'll 7 ask you, do you know what he was referring to in 8 the context of that meeting? 9 MR. WAGNER: I object to the form of the 10 question. 11 A The number of other compounds in the caustic 12 insoluble oil. 13 Q Other than the TCDD? 14 A Yes. 15 Q Was the location of this meeting at the 16 biochemical research laboratory, 1701 building, or 17 was it someplace else? 18 A I don't remember which building it was in. 19 Q But it was on the Dowpremises? 20 A Y e s . 21 Q On page 2 of Plaintiff's Exhibit 2, you mention 22 that Dr. Holder reviewed the medical side of the 23 Dow experience. He was the fellow that you 2262 104 1 referred to earlier that was head of the medical 2 division? 3 A I didn't say he was head of the medical division. 4 He was the gentleman I dealt with at the medical 5 department, yes. 6 Q Sorry. And you refer to the fact that he said we 7 now have approximately 60 to 70 cases of 8 individuals with chloracne, ranging from two 9 severe cases to some very mild cases that were 10 difficult to diagnose. Are you referring to, 11 there, just the cases from the 199 building? 12 A I couldn't tell you. 13 MR. WAGNER: I object to the form of the 14 question. 15 A I couldn't tell you what Dr. Holder was referring 16 to at the time. 17 Q You mention that he showed slides of the more 18 dramatic cases. Did you have a chance to observe 19 the slides yourself? 20 A Yes. 21 Q Did he put them in a slide projector and put them 22 up on a screen, is that the way he did that? 23 A Yes. 2263 O . a 2>to 105 1 Q Do you remember how many slides there are that he 2 showed? 3 A No. 4 Q You mention thathe reviewed clinicalstudies that 5 were being made on these people with emphasis on 6 the liver function tests. Do you recall what he 7 said about the impact of these unknown acnegens 8 and the TCDD on liver functions? 9 A I do not recall what he said. 10 Q You mention that Dr. Holder alsodiscussed or 11 mentioned the incidence of fatigue among the 12 afflicted people. Do you recall what he said 13 about that? 14 A No. 15 Q Do you recall Dr. Holder's discussion of what 16 topical treatments were tried on the 17 chloracnogenic condition of these folks? 18 A I do not. 19 Q You mention a doctor in the first full paragraph, 20 a Dr. Sadek, S-A-D-E-K, showed slides of ears and 21 livers of rabbits that had been exposed to TCDD. 22 Who is Dr. Sadek? 23 A He was, at that time, a veterinary pathologist in 2264 V' 3-361 106 1 the toxicology lab. 2 Q With Dow Chemical Company? 3 A Yes. 4 Q You also made a presentation at thatmeeting, is 5 that correct? 6 A I don't remember. 7 Q It mentions, here at the bottom ofpage 2 of 8 Plaintiff's Exhibit 2, that Silverstein described 9 the plant study on washing of contamination of 10 tools and surfaces. Does that refresh your 11 recollection? 12 A Yes. 13 Q And you can look at this to further refresh your 14 recollection, if you would like. It's at the very 15 bottom of page 2 of Plaintiff's Exhibit 2. Was it 16 your experience with contamination that in order 17 to remove it from tools and other objects, that 18 you either had to use the chemicals referenced in 19 that paragraph there or proceed with vigorous 20 scrubbing with soap and water to do that? 21 MR. WAGNER: I object to the form of the 22 question. 23 A I need a rerun of the question because it got a 2265 3 3 k a. 107 1 little long. 2 Q Okay. Was it your experience with the 3 contamination of tools and other objects with this 4 foreign material that you either had to use the 5 substances you outlined to remove it or to use 6 soapy water, soap and water with vigorous 7 scrubbing? 8 MR. WAGNER: I object to the form of the 9 question. 10 A Yes. 11 Q Did you feel, and having looked at this now, that 12 washing with water alone would be sufficient to 13 remove the contamination? 14 MR. WAGNER: I object, no predicate. 15 A My recollection is it could be done. 16 Q With water alone? 17 A Mm-hmm -- yes. I'm sorry, you said water alone? 18 Q Yes. 19 A Water, detergents and vigorous scrubbing was 20 required. 21 Q The question, though, is, did you feel that the 22 use of water alone would be insufficient without 23 detergent? 2268 108 1 A I think I missed a word in there, a key word. 2 Q Did you feel that water alone without detergent 3 would be insufficient? 4 MR. WAGNER: I object to the form of the 5 question. 6 A Yes. 7 Q You mention in the next paragraph on page 3 of 8 Plaintiff's Exhibit 2 that Harold Gill discussed 9 the analysis by vapor phase chromatography, and at 10 that time he referred to a limit of one part per 11 million for trichlorophenol and for 2,4,5-T acid, 12 either acetic or propionic. Is that your 13 recollection of the limit of detection of the 14 machinery at that time? 15 A At the time -16 MR. WAGNER: I object to the form of the 17 question, since the paragraph refers to two limits 18 of detection. 19 A My recollection at the time, for the sentence 20 highlighted, yeah. 21 Q You mention, at the bottom of page 4 of 22 Plaintiff's Exhibit 2, some concern, and we 23 discussed earlier, about as a group, that we could 2267 V-3l3(o^ 109 1 not afford to sell contaminated products. Was 2 that because of the concern that the customers 3 would not be using the products under the same 4 conditions of health control and hygiene as your 5 workers would be? 6 MR. WAGNER: I object to the form of the 7 question/ over broad and vague. 8 A I honestly can't remember that. 9 Q Do you have any independent recollection of the 10 comments of any of the other manufacturers' 11 representatives at this meeting with regard to 12 Dow's disclosure of this contaminant in both 13 trichlorophenol and potentially in its end 14 products? 15 MR. WAGNER: I object to the form of the 16 question. 17 A I have no recollection of any comments by anyone 18 at the meeting at this time. 19 Q Do you have any recollection of what the reaction 20 of the other manufacturers' representatives were 21 from your observation/ standpoint? 22 A I don't remember. 23 Q At this point in time, I'm referring to the date 110 1 of this meeting, which was on March 24th, 1965, 2 had Dow developed the technology to attempt to 3 reduce the contamination of TCDD or other 4 chloracnogens in its end products or its 5 trichlorophenol? 6 MR. WAGNER: I object to the form of the 7 question. 8 A I honestly do not recall time frames that well. 9 Q You mention on page 5 of Plaintiff's Exhibit 2 10 that even if the vapor phase chromatography does 11 not detect TCDD, an animal response may still 12 occur. Where did you get that information? 13 A I didn't say that. 14 Q My question is, where did you get that 15 information? 16 A It would have come probably from toxicology. I 17 was just reporting what Jack Peterson said at that 18 point. 19 Q Who is Jack Peterson? 20 A He was an industrial hygienist in the same group 21 in biochemical research with myself at the time. 22 Q Is he still with Dow? 23 A No. 2269 111 1 Q Do you know where he's located now? 2 A I believe he's in San Diego in retirement. 3 Q You mention in the next to last paragraph on page 4 5 of Plaintiff's Exhibit 2 that some air samples 5 have shown activity on the animals. Were those 6 air samples that you collected? 7 A Yes. 8 Q And were they collected from the 199 building, is 9 that what you're referring to? 10 A I'm not sure, at this point, where they were 11 collected. 12 Q There is a postscript on Plaintiff's Exhibit 2, 13 that's page 6. Is that a postscript from Dr. 14 Rowe, or is that something that you wrote? 15 A The V.K.R. was his standard way of initializing 16 things, so I would interpret that to be from V.K. 17 Rowe. 18 Q The last paragraph on page 6? 19 A Yes. 20 THE DEPONENT: While you are collecting 21 your thoughts, let's take a break. 22 (Recess.) 23 BY MR. SCHULER: 2270 V-S'Sil 112 1 Q Let me show you this document. This doesn't 2 appear to have been one that was marked to Rowe's 3 deposition, either. 4 MR. WAGNER: Before you move on to that 5 document, I've asked Mr. Silverstein about the 6 individual who he recalls having chloracne, and 7 with your agreement that he -- I will let him 8 identify that person without waiving the right to 9 object to others, revealing others' names, with 10 your agreement, if the court approves, that I can 11 still seek to expunge this individual's name from 12 this record so it's not public record if he later 13 agrees with me or the judge later changes his 14 mind. 15 MR. SCHULER: I agree, that, you know, 16 you've objected to it, and the judge has overruled 17 it, and you certainly have the right to appeal or 18 petition for certiori, but I'm not going to 19 stipulate to another objection. The judge ruled 20 on i t . 21 MR. WAGNER: I didn't say that. I don't 22 want to, by letting him give you a name, let that 23 serve as a springboard for you saying, well, I've 2271 p-a.'ifcS 113 1 waived it for everybody else; I can't object. I 2 can't go to the 5th D.C.A. I don't want it to be 3 a waiver in any other context. 4 MR. SCHULER: In other words, the fact 5 that he discloses the name will not prevent you 6 from taking the appeal? 7 MR. WAGNER: Correct. 8 MR. SCHULER: I'll agree to that. 9 MR. WAGNER: Go ahead. 10 MR. LUTZ: The mystery guest. 11 Q Let me restate the question. 12 A I wish you would. 13 Q I asked you to identify any of those people that 14 you remembered that had sustained chloracne as a 15 result of exposure to chloracnegens in your 16 experience at Dow Chemical, and you thought for a 17 minute, and I think your answer was you remembered 18 one person, and I'll ask you the name of the 19 person. 20 A I remember only one name, Rose, R-O-S-E. 21 Q A man or a woman? 22 A That's a man. 23 Q Do you remember the first name? 2272 P-33^ 114 1 A No, I don't know. 2 Q Still alive? 3 A I have no idea. 4 Q Do you know where Mr. Rose worked, in what part of 5 the company? Did he work in the 199 building? 6 A Only that he worked had 199 building, yeah. 7 Q Do you know what his job function was? 8 A I do not remember it. 9 Q How did it come about that you met him or remember 10 him? 11 A I have no idea. 12 Q Was there something significant about him that was 13 different than the others, that's why you remember 14 him? 15 A Only that I was acquainted with him. 16 Q Was his case of chloracne worse than the others? 17 A I don't remember. 18 Q And this would have been about 1964 that you met 19 him? 20 A Yes. 21 Q You don't have any idea at this point whether he's 22 still with the company or still in Midland or not? 23 A No, I do not. 2273 a a 7o 115 1 Q Okay. I handed you a document, and I'll ask you 2 to review that particular document, if you 3 wouldn't mind. 4 A You want me to read the entire thing or -- 5 Q Just look at it to familiarize yourself with it. 6 A Okay. 7 Q Do you recognize that as being a document that you 8 authored? 9 A Yes. 10 Q Let's go ahead and -- is there a date on that? 11 A On the last page. 12 Q What is the date? 13 A February 24th, 1976. 14 (Plaintiff's Exhibit 3 was marked for 15 identification.) 16 Q Before I ask you some questions about Plaintiff's 17 Exhibit 3, Mr. Silverstein, do you know anything 18 about the facts of this case, Moyer versus Dow 19 Chemical, et al, case? 20 MR. WAGNER: To the extent you may have 21 been told anything by me, I instruct you not to 22 answer. If you've heard about it from a source 23 other than a lawyer, feel free to give him that. 2274 O-33'll 116 1 A The answer is no. 2 Q So you haven't looked at any depositions of 3 witnesses or parties or experts outside of what 4 the lawyer for Dow Chemical communicated to you, 5 you would have no knowledge of any of the facts of 6 this case? 7 A That is correct. 8 Q Plaintiff's Exhibit 3 appears to be a document 9 that you identified, and it's entitled, quote, 10 Chloracne in the Dow Trichlorophenol plant, close 11 quote, Circa, 1964, correct? 12 A Correct. 13 Q And it's broken down into various sections. It 14 says dictated February 24th, 1976, as you 15 testified earlier. Why was this dictated on 16 February 24th, 1976, do you recall? 17 MR. WAGNER: I object to the form of the 18 question. 19 A Yes, I do recall. It's because I was about to 20 transfer to Dow Badische -- 21 Q Which we spelled earlier, I think. 22 A -- in Williamsburg, and wanted that donebefore I 23 lef t . 2275 p- 237P- 117 1 Q Was this document, Plaintiff's Exhibit 3, 2 requested by someone, or was this done by you for 3 your own summary purposes? 4 A I don't remember. 5 Q Why did you want it done before you left? 6 A It would be strictly conjecture to answer that. 7 Q You have no clear recollection at this point in 8 time, is that correct? 9 A That's correct. 10 Q Do you know what file this was put into upon your 11 leaving? 12 A No, I don't. 13 Q This document appears to have been marked with 14 exhibit numbers from other litigation. Were you 15 ever questioned about this particular document in 16 other cases? 17 A I don't rememberspecifically. 18 Q There appear to be some edit marks at various 19 points in this document. Do you know whether you 20 edited the document or whether it was edited by 21 someone else? 22 A I don't know. 23 Q Do you know whether this document was used for any 2276 D-A 313 118 1 purpose outside of keeping it in your own file 2 within the company? 3A I do not know. 4 Q Do you know whether this document was used for any 5 purpose outside of the company? 6 A I don't know that. 7 Q On page 5 of Plaintiff's Exhibit 3 you mention 8 that in February of 1964, the plant assistant 9 superintendent and some operators were examined by 10 the medical department and were found to have 11 chloracne. My question to you is, do you recall 12 the name of the assistant plant superintendent 13 that you were referring to there? 14 A Yes. 15 Q Who was that, sir? 16 MR. WAGNER: Same understanding with 17 referring to identifying the person's name? 18 MR. SCHULER: Yes. 19 A I can answer? Al Lueck, L-U-E-C-K. 20 Q And that is the Mr. Lueck who I think appeared on 21 the routing slips for some of the other memoranda? 22 MR. WAGNER: Object to the form of the 23 question. 119 1 A Yes. 2 Q Do you recall whether Mr. Lueck had a severe, mild 3 or moderate case of chloracne? 4 A I don't recall that. 5 Q Do you know where Mr. Lueck is located now? 6 A No. 7 Q Do you know if he's still employed with Dow 8 Chemical Company? 9 A To my knowledge, yes. 10 Q At Midland someplace? 11 A As far as I know, that's why I said noearlier. 12 Q Do you remember the names of any ofthe operators, 13 who you referred to on page 5, who reported to the 14 medical department or were examined by the medical 15 department and were found to have chloracne? 16 A No. 17 Q When you say operators, do you recall how many 18 there were in the plant, or is that just a generic 19 description for the people who worked in the 20 process in the plant? 21 A Yes. 22 Q The latter? 23 A The latter,yeah. p. 23*7^ 120 1 Q You mention on page 7 that you, Larry Silverstein, 2 were the first full-time safety officer. Are you 3 referring to in any of the plants or this 4 particular building 199? 5 A Referring to 199. 6 Q Were there other safety officers for other 7 manufacturing buildings? 8 A I do not know. 9 Q You mention on page 8 of Plaintiff's Exhibit 3 10 that thorough safety training indoctrinations for 11 all persons working in that plant were held. Do 12 you recall the frequency of those safety training 13 indoctrinations? 14 A I don't. 15 Q Were those meetings that youconducted? 16 A I don't remember. 17 Q Did you have any assistants that helped you to or 18 that would have conducted meetings like that? 19 MR. WAGNER: I object to the form of the 20 question. 21 A Repeat the question. 22 Q Were there any assistants that would have 23 conducted these safety training indoctrinations 2279 D-937C. 121 1 for persons working at the plants? 2 A No. 3 Q You mention on page 10 of Plaintiff's Exhibit 3 4 that you were one of the persons who went to 5 Europe, in late 1964, to talk to companies who had 6 experienced a similar problem and claimed to have 7 found answers to it, and you mention the one 8 French company and a German company. Does that 9 help refresh your recollection at all about who 10 the companies may have been? 11 A Well, I think I've mentioned Boehringer in 12 Germany. 13 Q Do you recall the French company or the other -14 A I think the French is Progil, P-R-O-G-I-L. 15 Q You mention on page 11 of Plaintiff's Exhibit 3 16 that while the caustic insoluble oil in the new 17 process still contains a few parts per million of 18 the known acnegen that caused our trouble in the 19 old plant, it is orders of magnitude less than was 20 found to be in the old plant's Cl oil. With 21 regard to that statement, are you referring to the 22 new process as being that process that was 23 purchased, if you will, from the German company 2280 0 5,377 122 1 and that was installed at Midland sometime after 2 1964? 3 A Yes. 4 Q And you mention that the contaminant was orders of 5 magnitude less than was found in the old Cl oil. 6 Do you recall what the numbers were? 7 A No. 8 Q Now, I'm going to jump over to page 14 ofyour 9 memorandum we have marked as Plaintiff's Exhibit 10 3, and you mention that your recollection was, at 11 the beginning of the company's quality control 12 guideline, was that the product must contain less 13 than one part per million by weight of TCDD. Does 14 that comport with your recollection today? 15 MR. WAGNER: Object to the form of the 16 question. 17 A Yes. 18 Q And then you go onto say that improvements in the 19 analytical method came about so that this quality 20 control limit was reduced to .05, and now stands, 21 you said, I believe, at .01 parts per million in 22 the final product. Is that the limit or the 23 standard that existed, to your recollection, when 2281 123 1 you did this memorandum in February of 1976? 2 MR. WAGNER: I object to the form, 3 compound. 4 A To the best of my recollection, yes. 5 Q And when you mention that the standard was .01 6 parts per million in the final product, are you 7 referring to the Silvex and 2,4,5-T? 8 A I do not recall. 9 Q In the next sentence you mention that all of this 10 quality control analysis data for the production 11 from the new plant has been retained by plant 12 supervision and is available if needed or desired. 13 What type of data, as you recall, would be kept by 14 plant supervision? 15 MR. WAGNER: I object to the form of the 16 question. 17 A I honestly couldn't answer that. 18 Q When you refer to plant supervision, what are you 19 referring to? 20 A Plant superintendent. 21 Q For that particular building? 22 A Yes. 23 Q In other words, if I wanted to get -- if I wanted 2282 D-9-37'? 124 1 to look at that documentation or data, to the best 2 of your recollection, anyway, back in 1976, that 3 data would have been located in some file at the 4 plant, itself, 199? 5 A Yes. 6 Q You mention in the next paragraph that there was 7 instituted, although not quite so rigid, quality 8 controls by analysis backed up by animal testing 9 for the end product into which the trichlorophenol 10 went, namely the esters, and so there was quality 11 control data available on that, as well. Are you 12 referring there to the end product, to the esters 13 2,4,5-T? 14 A Let me see the statement. 15 Q Sure. 16 A It would refer to the esters specifically, as I 17 read it. 18 Q The esters of 2,4,5-T? 19 A If you're -- if you're using 2,4,5-T to denote the 20 trichlorophenol, yes. 21 Q What I'm referring to is the end product -22 A Yeah. 23 Q -- that the trichlorophenol was a component of? 2283 125 1 A Mm-hmin. 2 Q The esters of2,4,5-T? 3 MR. WAGNER: Object to the form of the 4 question. 5 A Yes. 6 Q What about the amine form, do you know if there 7 was information, the same information in the amine 8 form? 9 A By amine, do you mean A-M-I-N-E -- 10 Q Yes, of -- 11 A -- meaning the amine? 12 Q Right. 13 A I do not know. 14 Q You mention, on page 15, that you prepared a 15 safety precautions brochure of five or six pages 16 regarding the handling or laboratory handling of 17 the TCDD. Do you know where that would be located 18 within the company? 19 MR. WAGNER: It's the one he provided to 20 the government? 21 MR. SCHULER: Yes. 22 Q Do you know where that would be in the company? 23 A No, I don't. 2284 V 23'S'l 126 1 Q Going back to page 13, you mentioned that there 2 was also developed a list of known 3 acnegen-producing materials by the company. Do 4 you know where that would be kept? 5 MR. WAGNER: Object to the form. 6 A No. 7 Q There's an insertion here, regarding human 8 testing, after page 13, is that in your 9 handwriting? 10 A Unfortunately it appears to be, yes. 11 Q That human testing that you're referring to, does 12 that refer to the testing that was done on jail 13 inmates, I think it was the Harrisburg prison? 14 A I don't know at what prison, but it says the 15 consulting dermatologist, yes. 16 Q Do you recall the name of the doctor who did that? 17 A Kligman. 18 Q So you're referring to the Kligman testing here on 19 page, the handwritten page 13? 20 A Yes. 21 Q There's a graph here that deals with response of 22 rabbits and humans to TCDD. Is that something you 23 prepared, or was that prepared somewhere else? 2285 V- 127 1 A I prepared this originally, yes. 2 Q And where did you get the information to prepare 3 this from? 4 A The human data came from Kligman's report. The 5 animal data came from Dow toxicology. 6 Q Back in 1976, when you prepared this report, was 7 it your understanding that the Kligman work was a 8 valid scientific experiment? 9 MR. WAGNER: Object to the form of the 10 question; undefined terms, vague and over broad. 11 A At the time it was considered, I believe, to be 12 valid information. 13 Q And would you have gotten the information 14 regarding the Kligman prisoner experiments from 15 the toxicology department? 16 A Y e s . 17 Q To yourknowledge, were any follow-up studies done 18 of those Dow workers that were exposed to TCDD in 19 1964 and who showed evidence of chloracne? 20 A Yes. 21 Q Can you tell me who conducted those follow-up 22 studies? 23 A Epidemiology section of the samelaboratory. 2286 P-S393 . . .. !...... 128 1 Q Of the toxicology laboratory? 2 A Well, toxicology, epidemiology, industrial hygiene 3 were all in health and environmental research back 4 then. 5 Q Do you recall the name of the individual or 6 individuals who conducted the follow-up studies? 7 A Dr. Ralph Cook, M.D., was the head of 8 epidemiology. 9 Q Was anyone else involved besides Dr. Cook? 10 A Yeah, a number of folks. 11 Q Do you recall any of the other names? 12 A Not for that time period. 13 Q Do you recall for how long the follow-up studies 14 were done? 15 MR. WAGNER: Object to the form of the 16 question. 17 A I don't understand your question. Do I -- 18 Q How long were the workers followed after 1964? 19 A I really don't know the answer. There's a 20 publication on it, but I don't remember when it 21 came out. 22 Q Do you remember what decade it came out, the 23 sixties, seventies, eighties? 2287 D-S3SY 129 1 A I think it was the seventies, but even that is 2 vague. 3 Q Do you recall the results of the follow-up study? 4 A To my recollection, there was no excess of any 5 disease found, and they were looking especially 6 for cancer and found no statistical significance 7 in terms of the fate of those people who passed 8 on. 9 Q Do you recall whether the study was published in a 10 scientific journal or not? 11 A Yes. 12 Q Do you recall what journal it was published in? 13 A I believe it was the Journal of Occupational 14 Medicine. 15 Q And indirectly I asked you this before, but do you 16 recall what year it may have been published? 17 A I don't remember the year. 18 Q As far as your responsibiliy is concerned, I take 19 it from what you're telling me that you did not 20 participate in the follow-up study, is that 21 right -- 22 A No, that's not -- 23 Q -- as an industrialhygienist? 2288 0-331^ 130 1 A No. 2 MR. WAGNER: Object to the form. 3 Q Did you? 4 A Yes. 5 Q What did you do? 6 A I estimated the categories of exposure for the 7 workers being studied. 8 Q Were yourresults committed to writing? 9 MR. WAGNER: In a form other than the 10 article that was published? 11 MR. SCHULER: Yes. 12 A I don't recall. 13 Q Do you remember what the results were of your 14 estimation of the exposure? 15 A No, sir. 16 Q And I say that, I mean, can you give me a range? 17 A Not a numerical range. 18 Q But that information would be in the article? 19 A In the article, correct, yeah. 20 Q Did you do anything else other than estimate 21 exposures in connection with the follow-up study 22 of the 1964 workers? 23 A Not to my recollection. 2289 P- 131 1 Q To your knowledge, and this was an in-house Dow 2 study, correct? 3 MR. WAGNER: Object to the form of the 4 question. Let me ask a clarifying question. Do 5 you mean all the authors were Dow employees? 6 MR. SCHULER: Correct. 7 MR. WAGNER: Okay. 8 A Yes. 9 Q And there wasn't anybody brought in from the 10 outside, any independent laboratory or scholars or 11 anybody to take part in the study? 12 MR. WAGNER: Object to the form of the 13 question. 14 A No. 15 Q Do you know whether there was anyone in that study 16 that died from cancer? 17 A I don't remember. 18 Q Well, you wouldn't remember then if there was 19 anyone that died from a specific type of cancer, 20 then, I assume? 21 A That's correct, I would not. 22 Q Have you participated in any other epidemiological 23 studies done within the Dow Chemical Company with 2290 132 1 regard to exposure to TCDD in humans? 2 A Not that I recall. 3 Q Is that the only one that you're aware of, the 4 1964 group? 5 A Yes. 6 Q Do you know whetheranyone was included inthat 7 study that did not evidence chloracne? 8 MR. WAGNER: I object to the form. 9 A I don't know. 10 Q Let me show you thisdocument, and I'll ask you if 11 you can identify that, and it's been marked as 12 Exhibit Number 17 to the deposition of Row. 13 THE DEPONENT: You guys have the worst 14 copying machines in the world. 15 MR. SCHULER: We got it from Dow 16 originally. 17 MR. WAGNER: It's not all his fault. 18 Q Would you identify that for the record, please? 19 A The document is a memo with a date that is 20 illegible, entitled the Hazard of Monsanto T Acid, 21 by L.G. Silverstein. Is that March 14th? I can't 22 tell. 23 (Plaintiff's Exhibit 4 was marked for 2291 !0' 133 1 identification.) 2 Q This was a memo that you had done regarding some 3 245T acid that Dow had purchased from Monsanto, 4 correct? 5 A That's correct. 6 Q And the material purchased from Monsanto was found 7 to contain TCDD in concentrations averaging about 8 ten parts per million, according to this, correct? 9 MR. WAGNER: Object to the form of the 10 question. 11 A I'd like to see it, here. 12 Q It's the bottom of the first paragraph. 13 A Yes. 14 Q And you were concerned because this product 15 constituted a hazard, is that correct? 16 MR. WAGNER: Object to the form of the 17 question. 18 Q In your opinion? 19 A That's correct. 20 Q And product was sold to Riverdale and Woodbury at 21 some point, correct? 22 A My recollection -- 23 MR. WAGNER: Object to the form of the 2292 D -P-3VJ 134 1 question. 2 A -- was that it was proposed to be transferred to 3 some other place, and those two names sound 4 familiar. I do not recall that it happened. 5 Q Well, look at the memorandum and see if the 6 memorandum refreshes your recollection. As a 7 predicate question, Woodbury and Riverdale are 8 what type of companies? 9 A I have no idea. 10 Q Don't you state in page 4 that the product was 11 already sold to those two companies? 12 MR. WAGNER: Object to the form of the 13 question. 14 A No, I don't read it that way, but I see in 15 paragraph two, I'm talking about the requirements 16 if we processed it in 199 and 349, and my 17 recollection is that's what we planned to do with 18 it when we got it, and it says Dow's involvement 19 in shipping this material to Riverdale concerns 20 me. It doesn't say we shipped it. I don't 21 remember it being shipped. I don't know. I just 22 don't know what happened to it. 23 Q Did Dow, in the 1970s, to your knowledge, purchase 2293 D-a3?o 135 1 2,4,5-T or 2,4-D from any other manufacturers for 2 resale to chemical suppliers? 3 MR. WAGNER: Object to the form, over 4 broad, vague. 5 A I do not know. 6 Q Who would know about something like that? 7 A I don't know that either. 8 Q Do you know whether there was any follow up from 9 this memorandum, looks like of March -- you're 10 right, it's hard to make out, it looks like March 11 15th, 1965, do you know whether there was any 12 follow up from this memorandum we marked as 13 Plaintiff's Exhibit 4? 14 A My recollection is that the material in question 15 was reprocessed within Dow Chemical until it was 16 non-detectable by analysis, and then it was 17 processed, but that's strictly my recollection at 18 this point. 19 Q Do you know who would have been responsible for 20 the reprocessing? 21 A No. 22 Q Do you recall any complaints from Dow customers 23 from, say, 1964 through 1976, regarding any 2294 136 1 chloracne from any of the 2,4-D or 2,4,5-T or 2 Silvex products sold by Dow? 3 MR. WAGNER: Object to the form of the 4 question. 5 A No. 6 Q If there were some complaints, would you be 7 involved in responding to those? 8 A No. 9 Q Do you know who would be involved in responding to 10 complaints from customers? 11 A No. 12 Q Do you recall any complaints from any Dow 13 customers or end users of 2,4,5-T or 2,4-D or 14 Silvex from 1964 through 1975, regarding it 15 causing -- the causing of cancer in any- users of 16 2,4-D, 2,4,5-T or Silvex? 17 MR. WAGNER: Object to the form of the 18 question, vague,over broad as to time, as well. 19 A No. 20 Q And I assume your answer would be thesame if 21 there were such complaints, you would not be 22 involved in responding to them, correct? 23 A That's correct. 2295 D- 93"%^. 137 1 Q Are you being paid for your time in testifying in 2 this case today? 3 A Yes. 4 Q And what's the compensation understanding that you 5 have regarding your time for the preparation or 6 time in deposition here for this case? 7 A My present employer is being paid for my time 8 spent here, and I will receive my normal 9 compensation from him. 10 Q That is Farlow EnvironmentalEngineers, Inc.? 11 A That's correct. 12 Q And what is your understanding of the compensation 13 arrangement to Farlow Environmental Engineers, 14 Inc., for your time involved in the preparation or 15 testimony in this case? 16 A For my services in legal areas, it's $150 an hour. 17 Q And that's for preparation and deposition time? 18 A Yes. 19 Q And is it your understanding that Dow Chemical 20 Company is paying that amount to Farlow? 21 A My understanding that Dow Elanco will pay Farlow, 22 yes. 23 Q And Dow Elanco is, to the best of your knowledge, 2296 P- 33=?3 138 1 a division or a part of Dow Chemical Company? 2 MR. WAGNER: Object to the form of the 3 question. 4 A In some way, yes. 5 Q Are you getting any portion of that $150 directly, 6 or do you get paid a salary as your compensation? 7 A I am paid a salary, yes. 8 Q Do you get any type of credit for that billing? 9 A No. 10 Q In other words, you hire your time out, your 11 employer charges for your time, and you get paid a 12 straight salary? 13 MR. WAGNER: Object to the form of the 14 question. 15 A That's correct. 16 Q And I assume the salary is based to some extent on 17 what you produce? 18 MR. WAGNER: I object. 19 A I didn't understand. 20 Q I assume your salary is based to some extent on 21 what you produce in terms of billing? 22 MR. WAGNER: Same objection. 23 A It's a straight salary, annual compensation, at 2297 ______________________ 139 1 this point. 2 Q I understand that, but I assume that it's based, 3 to some extent, on what you produce for the 4 company, billing-wise, right? 5 MR. WAGNER: Object to the form of the 6 question. 7 A That is not correct. 8 Q Do you know who J.E. Johnson was at Dow Chemical 9 Company back in 1969? 10 A There was a Julius Johnson who was a vice 11 president for research, I think. 12 Q Let me show you this document that's been marked 13 as Exhibit 24 to the deposition of Row, and I'll 14 ask you if you've ever seen it before? 15 A I have never seen this before, to my knowledge. 16 MR. SCHULER: So we have a record here, 17 let's mark this. 18 (Plaintiff's Exhibit 5 was marked for 19 identification.) 20 Q As part of Plaintiff's Exhibit 5, there's a 21 handwritten memorandum here, appears to be three 22 pages. Do you recognize who may have prepared 23 that? 2298 D-P39S' 140 1 MR. WAGNER: Object to the form of the 2 question, calls for speculation. 3 A The answer is no, I don't recognize that. 4 Q And you've never seen that handwritten memorandum 5 before? 6 A That's right, I have not. 7 Q Let me show you this document that's already 8 marked as Exhibit 20 to Row's deposition, and I'll 9 ask you if you've seen that before? 10 A I don't remember if I've ever seen it before. 11 (Plaintiff's Exhibit 6 was marked for 12 identification.) 13 Q In Plaintiff's Exhibit 6 -- before I get into 14 that, Mr. Axe signs this as a member of the safety 15 department, I think you testified earlier, and I 16 mentioned his name, that he was a member of the 17 same department that you were a member of, is that 18 correct? 19 A For a period of time, yes. 20 Q And he was also an industrial hygienist? 21 A Yes. 22 Q He mentions in Plaintiff's Exhibit 6 that there 23 was some reports of chloracne from what's called a 2299 J> St37fi 141 1 Tordon, T-O-R-D-O-N, plant. Are you familiar with 2 the chemical, Tordon? 3 A In a general sense, yes. 4 Q Does Tordon contain 2,4-D? 5 A I don't know. 6 Q Do you know of any of the chemical components of 7 Tordon? 8 A I couldn't name one of them, for you, no, I'm 9 sorry. 10 Q Are you familiar with a product named Kuron? 11 A No, I'm not. 12 Q How about Estron? 13 A A vague familiarity with that term. 14 Q Do you know whether either Kuron or Estron 15 contained 2,4,5-T or Silvex? 16 A I do not know. 17 Q In your assignment in connection with the 199 18 building, did you have occasion to deal with any 19 governmental entities regarding workers' safety in 20 1964, '65 or '66? 21 A No. 22 Q How about later years? 23 A No. 2300 V-33e?'7 142 1 Q Did you, yourself, Mr. Silverstein, ever contract 2 a case of chloracne? 3 A No. 4 Q Did you participate at all in the decision by the 5 Dow Chemical Company to withdraw 2,4,5-T or Silvex 6 from the market? 7 A No, sir. 8 Q Were you aware that thatdecision process was 9 going on at Dow Chemical Company at any point in 10 time? 11 MR. WAGNER: Object to the form of the 12 question. 13 A No. 14 Q Have youparticipated in any groups or, I'm not 15 talking about just in connection with your 16 employment with the Dow Chemical Company, but even 17 since your employment at 1979, participated in any 18 groups that have studied safety of 2,4-D as a 19 herbicide? 20 A No. 21 Q Do youbelong to anyprofessionalorganizations, 22 you told me what your educational background was, 23 but do you belong to any professional 2301 143 1 organizations or have you in the past belonged to 2 any professional organizations in connection with 3 your employment? 4 A Yes. 5 Q What organizations? 6 A The American IndustrialHygieneAssociation and 7 the Health Physics Society, and State chapters of 8 the Industrial Hygiene Association. 9 Q Have you held any positions with those 10 organizations at one time or another? 11 A Yes. 12 Q What type of positions have you held? 13 A Well, I was a member of, chairman of the 14 Laboratory Accreditation Committee for the 15 Industrial Hygiene Association. 16 Q How long ago was that? 17 A 15 years ago. Let's see, I can tell you, 1975, 18 '76, '77. 19 Q Any other positions? 20 A I was president of the now defunct Northeast 21 Michigan section of the American Industrial 22 Hygiene Association. That's it, I believe. 23 Q Do you have a curriculum vitae that you maintain, 2302 144 1 listing your educational background and various 2 organizations that you belong to? 3 A Yes. 4 Q Do you have a copy of that with you? 5 MR. WAGNER: I haven't seen it. I'll be 6 happy to get one for you. 7 MR. SCHULER: I think I asked for that 8 to be produced. If I don't have it, I can't ask 9 any questions about it. 10 MR. WAGNER: I didn't recall that, 11 frankly, but you may have. Have you got one here? 12 THE DEPONENT: All right, if we're going 13 into this, I need to take a break. 14 MR. SCHULER: That's fine. 15 (Recess.) 16 MR. SCHULER: Okay, let's go back on the 17 record. 18 Q Let me show you this document that you handed me, 19 Mr. Silverstein. If that wasn't intended to go 20 with it, you can take it off, if you want. 21 A You want the document? 22 Q I'm asking you to identify it for the record. 23 A I'm sorry, I see -- I didn't realize we were going 2303 145 1 on the record. This is a letter describing the 2 industrial hygiene services offered by Farlow 3 Environmental Engineers, Incorporated. 4 (Plaintiff's Exhibit 7 was marked for 5 identification.) 6 Q And this document here, if you would identify 7 that, please, sir. 8 A This is my resume', that of Lawrence G. 9 Silverstein, most recent copy, to my knowledge. 10 (Plaintiff's Exhibit 8 was marked for 11 identification.) 12 Q Looking at your resume' that we have had marked as 13 Plaintiff's Exhibit 8, you make the statement in 14 here that you have routinely worked with attorneys 15 on cases involving real or perceived injuries 16 related to exposure to hazardous materials in the 17 workplace. And my question to you is what kind of 18 numbers are we talking about here where you work 19 routinely with attorneys for real or perceived 20 injuries related to exposure to hazardous 21 materials? 22 A My draft of the document you are holding said 23 occasionally, or words to that effect, that 2304 D-S'/OI 146 1 routinely is a word substituted by my present 2 supervisor, when he revised my resume'. I have 3 done it occasionally, is more accurate. 4 Q Tell me about your occasional experience, then, at 5 working with attorneys in personal injury, toxic 6 tort cases? 7 A It's been -8 MR. WAGNER: Let me see it for a second, 9 excuse me. 10 Now, the question said the word toxic 11 tort, and I object to the form. The resume' 12 doesn't say that. 13 A I was going to say -- 14 MR. WAGNER: Listen to the question, and 15 I object to the form of the question. It's 16 undefined as to what toxic tort is. 17 Q How long have you been a gun for hire, that's what 18 I'm asking? 19 MR. WAGNER: I object to the form. You 20 don't have to answer that one. 21 Q How long have you been working with attorneys in 22 cases involving injuries from exposure to 23 hazardous substances, as you so eloquently worded 2305 147 1 it here? 2 MR. WAGNER: Object to the form of the 3 question. 4 A I'm trying to recall my first such event. I 5 believe it was in the mid-seventies, and the only 6 occasions on which I have worked with attorneys 7 since the mid-seventies were involved with cases 8 having to do with Dow Chemical Company. 9 Q And can you give me some idea of the numbers of 10 cases that you've been involved in since the 11 mid-seventies? 12 A Less than half a dozen. 13 Q And can you tell me what types of chemicals were 14 involved in the half a dozen cases? 15 MR. WAGNER: Object to the form of the 16 question. 17 A In all but one instance it involved the dioxins. 18 Q Can you give me the names of some of the cases? 19 A That, I cannot do. I don't remember. 20 Q Would the bulk of your being involved with 21 attorneys have been on Dow Chemical Company's 22 behalf? 23 MR. WAGNER: Object to the form of the 2306 ___________________________________________________p q - j o 3 148 A Yes.1 question. 2 3 Q I assume an attorney wouldn't hire you to testify 4 against a dioxin manufacturer while you were 5 working for Dow Chemical Company, or maybe I'm 6 wrong. Has that ever happened? 7 MR. WAGNER: Object to the form of the 8 question. 9 A Was there a question? 10 (The requested material was read by the 11 reporter.) 12 MR. WAGNER: Same objection, I object to 13 the form. 14 A I don't know. 15 Q You don't know? 16 A I don't know. You asked, has that ever happened? 17 That's a whole big universe. 18 Q Six cases doesn't sound like an universe to me. 19 What attorneys have you worked with who have hired 20 your services in the past? 21 A Give me the question again, please. 22 (The requested material was read by the 23 reporter.) 2307 149 1 A I'd like to question the wording of the question. 2 You said, hired me. I've never been paid by an 3 attorney, to my knowledge, for anything. 4 Q Well, let me explore that a little bit. You said 5 that you've routinely worked with attorneys on 6 cases involving real or perceived injuries related 7 to exposure to hazardous materials in the 8 workplace, and let me ask you what attorneys 9 you've worked with in that context? 10 MR. WAGNER: Object to the form of the 11 question. 12 A I have worked with attorneys representing the Dow 13 Chemical Company exclusively. 14 Q And I assume in the past that was probably the 15 Rivkin, Radler law firm for the time period you're 16 talking about from the mid-seventies? 17 A I don't know for sure. 18 Q Do you remember the names of any of the lawyers 19 that you worked with? 20 A Y e s . 21 Q Who were they, the ones that you remember? 22 A I remember one by the name of Sam Pierce. 23 Q Maybe I can shorten this up by asking you, have 2308 150 1 you been hired by any lawyers other than lawyers 2 representing Dow Chemical Company to work on this 3 type of case? 4 MR. WAGNER: Object to the form of the 5 question. 6 A No. 7 Q Since you left Dow Chemical Company in 1979, have 8 you or your firm been retained, other than this 9 case, have you or your firm been retained by any 10 other attorneys for Dow Chemical Company other 11 than the attorneys in this case? 12 MR. WAGNER: Object to the form of the 13 question, no predicate. 14 A I don't even understand the question. It was 15 confusing to me. 16 Q Okay. Have you ever testified in trial, 17 Mr. Silverstein, on behalf of Dow Chemical Company 18 in any case? 19 A No. 20 Q In your list of publications, you list or you make 21 the statement you co-authored an epidemiological 22 study on dioxin-exposed workers. Was that the 23 study we referred to earlier of the 1964 workers 2309 O ' 3-VOfc 151 1 at Dow Chemical? 2 A Yes. 3 Q And your name ison that study? 4 A Yes. 5 Q Other than the case that we have at hand here, the 6 Moyer case, is your company, Farlow, being paid by 7 DowElanco or Dow Chemical in any other cases, 8 presently? 9 MR. WAGNER: Object to the form of the 10 question. 11 A I don't know. 12 Q No other ones that you're involved in? 13 A None to my knowledge, sir. 14 Q You mention, also, in your resume, here, that you 15 are a senior IH, I assume that's industrial 16 hygienist, for dioxin, and then in Agent Orange 17 investigations. Is that in connection with the 18 1964 incident that we've discussed here, or is 19 that some other position that you held at the 20 company? 21 A The former. 22 Q When you havedioxin here, and then parentheses, 23 agent orange, are you equating the two? 2310 D'SWo7' 152 1 A No, sir. 2 Q Why did you put the agent orange in parentheses? 3 A Because to the lay people, agent orange is more 4 familiar than dioxin, presumably. 5 Q When you state manager of industrial hygiene 6 research and AIHA accredited laboratory, what does 7 the AIHA mean? 8 A American Industrial Hygiene Association. 9 Q Is that the laboratory that you're referring to, 10 was that the laboratory at Dow Chemical? 11 A Yes. 12 Q In connection with your work at Dow Corning 13 Corporation, I think you said you started there in 14 1979, have you testified in any lawsuits? 15 A No. 16 Q Do you consider dioxin to be a hazardous material? 17 MR. WAGNER: Object to the form of the 18 question. 19 A Yes. 20 Q You mention in this letter describing your 21 industrial hygiene services that you were the 22 first manager of industrial hygiene and safety for 23 the Dow Midland plant. Are you referring to that 2311 153 1 199 building or the combination of buildings 2 there? 3 A It refers to the Midland production division. 4 Q And you mention in the next sentence that this 5 facility was claimed to be the largest chemical 6 production plant at one site at that time. What 7 I'm trying to get at here is, you're referring to 8 the production of all chemicals generically that 9 were done at that location at Midland, or specific 10 types of chemicals? 11 MR. WAGNER: Object to the form of the 12 question. 13 A I don't understand your question, but -- 14 Q Let me make it clearer, then. I'm trying to get 15 at, were you the safety officer for the overall 16 production facilities for Dow? 17 A Y e s . 18 Q Okay. 19 A In Midland. 20 Q And that encompassed,I assume, the production of 21 many different types of chemicals? 22 A Yes. 23 Q Not just trichlorophenol or2,4,5-T or Silvex or 2312 154 1 2,4-D, but other chemicals, as well? 2 A Yes. 3 Q How many chemicals, do you know, did you ever get 4 a count? 5 A I have no idea. 6 Q In the hundreds? 7 A Easily. 8 Q Did you ever have any input into the writing of 9 any standards through OSHA or NIOSH, for example, 10 for dioxin or any related materials? 11 A I didn't understand your question. I missed a key 12 word someplace. 13 Q Let me repeat it. Did you ever have any input 14 into the writing of any OSHA or NIOSH standards 15 for dioxin or related materials? 16 A No. 17 Q Now, I've asked for some additional documentation, 18 here in the notice of deposition, that had to do 19 with documents that you produced or were produced 20 at your direction in the course of your employment 21 with Dow Chemical Company that pertain to 22 research, analysis, formulation, study or 23 production of 2,4-D, 2,4,5-T, Silvex or any 2313 Q'&HfO 155 1 product containing those chemicals. Do we have 2 any of those documents here today? 3 MR. WAGNER: He didn't have any, no. 4 MR. LUTZ: Not today, or he didn't have 5 any period? 6 MR. WAGNER: He didn't have any 7 documents responsive to the subpoena. 8 MR. SCHULER: You're not saying Dow 9 doesn't have the documents; you're saying he 10 doesn't have the documents? 11 MR. WAGNER: That's correct, it was a 12 subpoena to him. 13 Q You don't maintain any documents, is that correct, 14 Mr. Silverstein, you don't have any copies of 15 documents you generated at Dow Chemical Company? 16 A That's correct, I do not have copies. 17 Q You don't keep any files at home with any of your 18 work product from that, what was it, 20-year 19 employment history? 20 A No, I don't. 21 Q Do you have copies of the article that you 22 published on the epidemiological study? 23 A I believe I do have a copy of that. 2314 O'TMi/ 156 1 Q Do you have it with you here today? 2 A No, I don't. 3 Q That would also fit the description of what I have 4 requested here. 5 MR. WAGNER: I didn't know that you had 6 that -- I asked -- I think I've got a copy. 7 THE DEPONENT: Did you ask me if I had a 8 copy of that? 9 MR. WAGNER: Yes. 10 THE DEPONENT: No. I have it at home, 11 but not here. 12 MR. WAGNER: I've got a copy. 13 Q Let me show you, before I read further, let me 14 show you this particular document that your lawyer 15 has given to me, and I'll ask you to identify it. 16 A It is a copy of a published article. You want the 17 precise title? 18 Q Yes, please. 19 A Mortality Experience of Employees Exposed to 20 2,3,7,8-Tetrachlorodibenzo-para-dioxin, 21 parentheses, TCDD. 22 (Plaintiff's Exhibit 9 was marked for 23 identification.) 2315 O -3^ ip- 157 1 Q Incidentally, let me just go back, to digress for 2 a minute, with regard to Farlow, how many 3 employees are in Farlow? 4 A About 20. 5 Q And it's located here in Indianapolis? 6 A Yes. 7 Q And in the organization of the company, you 8 mention that you're director-industrial hygiene 9 safety and training. How is the company broken 10 down? Are there other specific sections of the 11 company? 12 A Well, there's an engineering group. That's pretty 13 much the rest of the company, except for 14 administration. 15 Q How many people are in the industrial hygiene 16 safety and training area? 17 A Three total. 18 Q And yourself, and who are the others? 19 A An industrial hygienist and an instructor, 20 training specialist. 21 Q What are the names of the other two people 22 involved? 23 THE DEPONENT: Is this all pertinent? 2316 D' 5.^//3 3 158 1 MR. SCHULER: Sure. 2 A Linda Jackowiac is the industrial hygienist. 3 Russell Farlow is the training specialist. 4 Q Do you hold any officialship in the company, 5 president or vice president, treasurer, anything 6 like that? 7 A No. 8 Q Do youhave any stockin thecompany? 9 A No. 10 Q Looking atthis article wehave marked as 11 Plaintiff's Exhibit 9, the mortality study done on 12 the 61 workers involved in the 1964 chloracne 13 incident, it's mentioned in the head note to the 14 article that there were three deaths attributed to 15 cancer out of the group, with 1.6 expected. Can 16 you tell me, and you can look at this -- 17 MR. WAGNER: What kind? It says what 18 kind at the very end. 19 MR. SCHULER: That's what I'm looking 20 for. 21 Q I know you told me earlier, but usually it tells 22 you what the journal is at the top. I don't see 23 that on this. Can you tell me again what journal 2317 O' 159 1 this was published in? 2 A I believe it was the Journal of Occupational 3 Medicine. 4 Q Can you tell me the year of publication 5 approximately? 6 A Somewhere in the seventies, I think. 7 Q Is there continued follow up of this group, if you 8 know? 9 A I do not know. 10 Q But you haven't participated in it, if there has 11 been? 12 A I have not participated, correct. 13 Q You mention that you were involved in calculating 14 the exposures, and I'm trying to read an obviously 15 very technical -16 MR. WAGNER: I think he said 17 characterizing, not calculating. 18 Q Okay, let me ask you to -- it looks like a table 19 that you may have done. Let me ask you to just 20 take a look at that and tell me how you 21 characterize the exposure. 22 A You're referring to this table? 23 Q Well, whatever you need to refer to answer the 2318 O- 5.41 S 160 1 question. 2 A From memory, I characterized the exposure based on 3 my familiarity with the plant environment, 4 physical layout and that type of thing, plus the 5 data in terms of wipe tests and air samples taken 6 through the event. And with all that information, 7 I could -- I did the best I could in judging high 8 versus low exposure, in essence. 9 Q Did you quantify it all or just put it in 10 categories, high, low? 11 A Not quantified, no. 12 Q So based on what you just said, if I understood 13 you correctly, through using the wipe tests and 14 the air sampling, and what was the third thing, 15 observing the workers, also? 16 A Yes. 17 Q You just kind of put them in groups of high or low 18 exposure? 19 A That's correct. 20 Q Other than to the characterization of the 21 exposure, I assume that the other conclusions in 22 the study were those of Dr. Cook, essentially? 23 MR. WAGNER: Object to the form of the 2319 161 1 question. 2 Q Would that be a fair statement? 3 A Yes. 4 Q Is Dr. Cook still with Dow? 5 A No. 6 Q Is he still around, still alive? 7 A Yes. 8 Q Where is he located now, if you know? 9 A Yes. 10 Q Where? 11 A Dow Corning Corporation. 12 Q Also in Midland? 13 A Yes. 14 Q How many hours, if you know, has your company 15 billed for your time so far in this matter? 16 A None. 17 Q How many hours have you accumulated to date in 18 this matter? 19 A I haven't really calculated yet. 20 Q Can you give me an estimate? 21 A Okay, hang on just a minute. 15 maybe. 22 Q Other than this article that's now been produced 23 as Plaintiff's Exhibit 9, do you have any other 2320 D'ZMin 162 1 documents in your possession, including reports, 2 articles, or transcripts relating to any opinion 3 you have ever formed regarding the cause of soft 4 tissue sarcoma or the toxicology or health effects 5 of exposure to 2,4-D, 2,4,5-T, Silvex, 2,4,5-T or 6 any product or substance containing any of these 7 chemicals? 8 A No. You asked if I have any documents pertaining 9 to all that, right? 10 Q That's correct. 11 A The answer is no, I do not. 12 Q Do you have any documents in your possession 13 relating to any instance since 1981 that you have 14 been employed by a party or his attorney in 15 connection with or related to litigation involving 16 personal injury or the risk of personal injury 17 allegedly cause by exposure to a pesticide, 18 herbicide or other chemical or substance? 19 A Oh, boy, I have, in my files at home, a statement 20 I made. I don't think it was even a deposition. 21 I do not know what case. I do not know for sure 22 if it's involved with your materials or not, but 23 that's the only thing I can remember, and I do not 163 1 have a copy of that with me. When I say at home, 2 I mean at home in Midland, Michigan, because I 3 didn't move it down here. 4 Q A statement made in connection with litigation? 5 A Yes, but I have no recollection of what case, what 6 materials. 7 Q When you say a statement, are you talking about a 8 deposition or -- 9 A I don't even know if it was a deposition, to be 10 honest with you. I believe it was a statement 11 made, and I was asked to review it for accuracy 12 and sign it if I agreed it was accurate. 13 MR. SCHULER: I would ask that that 14 statement be produced, as well, since you have 15 that in your possession. 16 MR. WAGNER: I haven't seen it, so I'll 17 have to get it. I don't know if it's a work 18 product statement or not. 19 A I just have no idea what it relates to, but in the 20 interest of outright honesty, I had to tell you 21 I've got it. I don't know what it is. 22 MR. WAGNER: I'll have to look at i t . I 23 need to make a telephone call. 2322 D - a H i "? 164 1 (Recess.) 2 BY MR. SCHULER: 3 Q Let's go back to where we were. You had mentioned 4 that you had some type of statement or affidavit 5 or something along those lines in your records, 6 Mr. Silverstein, at home? 7 MR. WAGNER: In Midland. 8 Q On some other case? 9 A Yes. 10 Q Do you still have ahome there? 11 A Yes. 12 Q And I've requested that be produced. Obviously 13 I'm in a whipsaw here, because I can't ask you any 14 questions about it. 15 MR. WAGNER: In the break I tried to get 16 in touch with a Dow lawyer to find out -- it's the 17 first I heard of the statement, and I tried in the 18 quick break to find out whether or not it is a 19 work product statement or what it is, and I was 20 unsuccessful in tracking down the lawyer I need to 21 talk with. 22 THE DEPONENT: I'm certain it's not a 23 deposition. That, I know. 2323 O -3-4^0 165 1 MR. SCHULER: But, I mean, my position 2 for the record is I'm obviously here, I've 3 requested that certain documents be produced, and 4 if that document fits the subpoena and was not 5 produced, I can't ask any questions about it 6 without seeing it. 7 THE DEPONENT: You do understand it's a 8 copy? 9 MR. SCHULER: I understand. Copies are 10 not an issue here. The issue is the statement, 11 itself. And I reserve the right to question this 12 witness on any items that are not produced that 13 fit the description of the subpoena that he may 14 have. 15 Q Let me go down the remaining documents here. The 16 next request was for all documents relating to 17 every instance since 1981 that you have been 18 employed by a party or his attorney in connection 19 with or related to litigation involving personal 20 injury or the risk of personal injury allegedly 21 caused by exposure to a pesticide, herbicide or 22 other chemical or substance. Other than the 23 document you mentioned, do you have any other 2324 166 1 documents that would fit that description? 2 A No. 3 Q The next request was for all documents relating to 4 any opinion you have communicated or formed since 5 1981 in connection with any employment or 6 professional services rendered as an expert 7 witness or consultant, including but not limited 8 to deposition transcripts, contracts, reports, 9 trial transcripts, correspondence, or documents 10 summarizing any opinion formed and the grounds for 11 your opinion. Do you have any documents that fit 12 that description? 13 A No, sir. 14 Q Do you have any documents in your possession that 15 you obtained from the defendants in this case or 16 their attorneys, through either this lawsuit or 17 other lawsuits? 18 A No, sir. 19 Q Do you maintain files at home with regard to the 20 cases in which you have consulted attorneys in 21 other lawsuits? 22 A No. 23 Q This statement or affidavit or whatever it is that 2325 V a'-iaa- 167 1 you do have, what kind of a file do you keep that 2 in? 3 A Miscellaneous. 4 Q In that miscellaneous filefolder, isthere any 5 other documents that pertain to litigation 6 concerning Dow Chemical Company or any other 7 company, for that matter? 8 A No. 9 Q Have you ever beenretained ortestified on behalf 10 of a plaintiff injured as a result of exposure to 11 a chemical or toxic substance? 12 A No. 13 Q In yourconnection with youremployment with Dow 14 Chemical Company and subsequent employment with 15 Dow Corning and your subsequent employment with, 16 as a consultant with Farlow Environmental 17 Engineers, do you have an opinion as to whether or 18 not there is any safe level of exposure to TCDD? 19 MR. WAGNER: Object to the form of the 20 question. 21 A No, I do not. 22 MR.SCHULER: That's all I've got. 23 Thank you. 2326 168 1 MR. LUTZ: No questions. 2 MR. WAGNER: He'll read it. 3 AND FURTHER THE DEPONENT SAYETH NOT 4 5 LAWRENCE G. SILVERSTEIN 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 2327 D9-4S.H 169 1 STATE OF INDIANA ) ) ss: 2 COUNTY OF MARION ) 3 I, Aprille Rigsbee Lucas, RPR, Notar 4 Public in and for the County of Marion, State of 5 Indiana, do hereby certify that the deponent 6 herein was by me first duly sworn to tell the 7 truth, the whole truth and nothing but the truth, 8 in the aforementioned matter; 9 That the foregoing deposition was taken 10 on behalf of the Plaintiff; 11 That said deposition was taken at the 12 time and place heretofore mentioned between the 13 hours of 8:00 a.m. and 6:00 p.m; 14 That said deposition was taken down in 15 stenograph notes and afterwards reduced to 16 typewriting under my direction and thereafter 17 presented to said witness for signature; that this 18 certificate does not purport to acknowledge or 19 verify the signature hereto of the deponent; 20 I do further certify that I am a 21 disinterested person in this cause of action; that 22 I am not a relative or attorney of any of the 23 parties, or otherwise interested in the event of 2328 P 2-43-^r 170 1 this cause of action, and am not in the employ of 2 the attorneys for any of the parties. 3 IN WITNESS WHEREOF, I have hereunto set 4 my hand and affixed my notarial seal this 15th day 5 of March, 1993. 6 7 Siprille Rifc^bee^TTucas , RPR 8 My Commission Expires: 9 September 21, 1996 10 11 12 13 2329 1 UNITED STATES DISTRICT COURT 2 EASTERN DISTRICT OF ARKANSAS, WESTERN DIVISION 3 4 JERRY KEISTER,et al., ) ) 5 *- Plaintiffs, ) ) 6 -vs- ) ) 7 THE DOW CHEMICAL COMPANY, ) ) et al., ) 8) Defendants. ) 9 _________________________________ ) 10 11 DEPOSITION OF LAWRENCE 6. SILVERSTEIN 12 Taken by the Plaintiff on the 18th day of July, 13 1990, at Sheraton Fashion Square Hotel, 4960 14 Towne Centre Road, Saginaw, Michigan, at 9:00 a.m. 15 APPEARANCES 16 For the Plaintiffs: 17 18 MR. GARY DAVIS Gilreath & Associates P.O. Box 1270 Knoxville, TN 37901 (615) 637-2442 19 For the Defendant The MR. STANLEY PIERCE Dow chemical Company: Rivkin, Radler, Bayh, Hart & Kremer 20 EAB Plaza West Tower - 11th Floor 21 Uniondale, NY 11556 (516) 357-3000 22 MR. STEPHEN J. KRIGBAUM 23 The Dow Chemical Company 2030 Willard H. Dow Center 24 Midland, MI 48674 (517) 636-0571 GENERAL REPORTING SERVICE, INC. 2330 O S W 3 - 7 1 united states district court 2 EASTERN DISTRICT OF ARKANSAS, WESTERN DIVISION 3 4 JERRY KEISTER,et al.f ) ) ) 5 Plaintiffs, ) 6 -vs- ) ) 7 THE DOW CHEMICAL COMPANY, ) ) et al., ) 8) Defendants. ) 9 ________________________________________________________________________ ) 10 11 DEPOSITION OF LAWRENCE 6. SILVERSTEIN 12 Taken by the Plaintiff on the 18th day of July, 13 1990, at Sheraton Fashion Square Hotel, 4960 14 Towne Centre Road, Saginaw, Michigan, at 9:00 a.m. 15 APPEARANCES : 16 For the Plaintiffs: 17 18 MR. GARY DAVIS Gilreath & Associates P.O. Box 1270 Knoxville, TN 37901 (615) 637-2442 19 For the Defendant The MR. STANLEY PIERCE Dow Chemical Company: Rivkin, Radler, Bayh, Hart & Kremer 20 EAB Plaza West Tower - 11th Floor 21 Uniondale, NY 11556 (516) 357-3000 22 MR. STEPHEN J. KRIGBAUM 23 The Dow Chemical Company 2030 Willard H. Dow Center 24 Midland, MI 48674 (517) 636-0571 25 GENERAL REPORTING SERVICE, INC. 2331 p- 3.^5-"5 1 APPEARANCES (Continued): < 2 For the Defendant Hercules Powder: 3 MS.'LEEANN JONES Powell, Goldstein, Frazer & Murphy 400 Perimeter Center Terrace Suite 1050 4 Atlanta, GA 30346 (404) 399-2800 5 REPORTED BY: J. Richard Loberg, RPR, CSR-2135 6 Certified Shorthand Reporter (517) 793-6672 1-800-878-6672 7 FAX: (517) 793-4290 8 9 10 --oOo-- 11 12 TABLE OF CONTENTS 13 14 LAWRENCE G. SILVERSTEIN PAGE 15 16 Examination by Mr. Davis Examination by Ms. Jones 17 Examination by Mr. Davis 3 78 90 18 19 MARKED 20 DepX#l Letter (7-30-64) DepX#2 Memo (3-11-65) 21 DepX#2-A Report (9-28-64) DepX#3 Process Drawing 22 DepX#4 Lab Notes DepX#5 Report (2-24-76) 23 DepX#6 Letter (2-11-57) DepX#7 Memo (11-13-64) 24 DepX#8 Memo (lr25-65> DepX#9 Memo (12-22-64) 25 DepX#10 Report (10-9-64) 10 16 19 18 18 18 18 18 18 18 18 GENERAL REPORTING SERVICE, INC. 2332 O- 3 1 EXHIBITS (Continued) MARKED 2 DepXlll Memo (3-10-65) DepX#12 Summary (2-10-70) 3 DepX#13 Letter (4-10-70) DepX#14 Memo (5-4-65) 4 DepX#15 Memo (8-16-66) DepX#16 Memo (8-16-66) 5 DepX#17 Letter (1-17-67) ** DepX#18 (Not identified) 6 DepX#19 Report - NaTCP ** DepX#20 (Not identified) 7 DepX#21 Meeting Notes (8-25-64) DepX#22 Memo (3-29-65) 8 18 18 18 18 18 18 18 18 18 18 18 78 9 ** Exhibits Retained by Plaintiff's Attorney 10 11 12 -oOo- 13 14 15 LAWRENCE G. SILVERSTEIN 16 HAVING BEEN CALLED BY THE PLAINTIFF AND SWORN: 17 EXAMINATION 18 BY MR. DAVIS: 19 Q Mr. Silverstein, my name is Gary Davis and I represent 20 a group of workers and their families from 21 Jacksonville, Arkansas, and one of the defendants in 22 this case is Dow Chemical. I'm here to ask you some 23 questions today. Have you been in a deposition before? 24 A Yes, sir. 25 MR. PIERCE: Mr. Davis, would you indicate on GENERAL REPORTING SERVICE, INC. 2333 V 5.^30 4 1 the record why we're starting at this time, please? 2 MR. DAVIS: Sure. I apologize to all 3 concerned that someone dropped the ball in our office 4 and ve did not have a court reporter show up at the 5 appointed hour and we're starting approximately an hour 6 late. 7 MR. PIERCE: And let me indicate to you that 8 the witness has a hearing problem, he has hearing aids, 9 and if you could please.speak up and also the rattling 10 of paper sometimes causes difficulty. 11 MS. JONES: Gary, -- 12 MR. DAVIS: Can you hear us? 13 MS. JONES: You guys were cut off there for a 14 minute. 15 MR. DAVIS: I don't understand what's going on 16 here. 17 MS. JONES: I think it has something to do 18 with your speaker because it's cutting in and out. 19 MR. DAVIS: I don't know what to do, LeeAnn, 20 we got a speaker phone here. Can you hear now? 21 MS. JONES: Yes, I can hear you fine now. 22 MR. DAVIS: We'll go on. 23 Q (By Mr. Davis, continuing): Mr. Silverstein, if you 24 are unable to hear me at any point during the 25 deposition please let me know or if you don't GENERAL REPORTING SERVICE, INC. 2334 0-3^31 5 1 understand my question because I haven't phrased it 2 well enough, please let me know about that. 3 A I will. 4 Q Okay. Thanks. Can you state your full name, please? 5 A Lawrence Gordon Silverstein. 6 Q And where do you live? 7 A Midland, Michigan. 8 Q Okay. Can you give me your address, please? 9 A 5409 Mason Street. 10 MS. JONES: Gary, you guys are gone again. 11 (Conference off the record.) 12 Q Mr. Silverstein, you were giving me your address. 13 A 5409 Mason Street in Midland, Michigan 48640. 14 Q Thank you. Are you currently employed? 15 A Yes, sir. 16 Q And who are you employed with? 17 A The Dow Corning Corporation, Midland, Michigan. 18 Q Okay. And how long have you been with Dow Corning? 19 A Ten years, round figures. 20 Q Before you were with the Dow Coming Corporation were 21 you with The Dow Chemical Company? 22 A Yes, sir. 23 Q And where was that? 24 A Primarily Midland, Michigan. 25 Q When did you first start working for Dow Chemical? GENERAL REPORTING SERVICE, INC. 2335 6 1 A September 1st, 1955. 2 Q What was your position at that time? 3 A I was an industrial hygienist. 4 Q In which particular plant did you work? 5 MR. PIERCE: Objection to the form of the 6 question. You go ahead and answer. 7 A Mostly the Midland, Michigan production plant. 8 Q So you started in 1955 in Midland. Can you tell me 9 what the Midland production plant is? Is that the 10 major production facility of The Dow Chemical Company? 11 MR. PIERCE: Objection to the form of the 12 question. 13 A I don't know for sure. I was told it was at that time. 14 MR. DAVIS: Off the record just a second. 15 (Conference off the record.) 16 Q (By Mr. Davis, continuing): The Midland, Michigan 17 plant for Dow Chemical, do you know approximately how 18 many employees it has? 19 A No, I don't. Not at this time. 20 Q How about at the time you were working there? 21 A I don't remember. 22 Q Thousands? 23 MR. PIERCE: Objection to the form of the 24 question. The man answered he doesn't know. 25 Q Was it in the thousands* as far as you know? GENERAL REPORTING SERVICE, INC. 2336 P-24 33 7 1 A As far as I know. 2 Q And is Dow's headquarters in Midland, Michigan? 3 A Yes. 4 Q Which particular production units did you have 5 responsibility for when you started in 1955? 6 MR. PIERCE: Objection to the form of the 7 question. 8 A No assignment to a particular plant at that time. 9 Q Okay. When were you first involved in the production 10 units that made trichlorophenol and 2,4,5-T at the Dow 11 plant? 12 MR. PIERCE: Objection to the form. No 13 foundation. 14 A To the best of my recollection, about 1964. 15 Q Okay. You were aware that Dow had been making 16 trichlorophenol all the way back to 1946, weren't you? 17 MR. PIERCE: Objection to the form of the 18 question. 19 Q You may answer. 20 A I became aware of that fact, yes. 21 Q And that Dow was making 2,4,5-T as an herbicide prior 22 to 1964? 23 MR. PIERCE: Objection to the form of the 24 question. 25 A I really couldn't, you know, speak accurately on that. GENERAL REPORTING SERVICE, INC. 2337 p-aw3sf 8 1 Q Okay. You knew that Dow was making 2,4,5-T before you 2 started working in the production unit that made those 3 products, didn't you? 4 HR. PIERCE: Objection to the form. Asked and 5 answered. 6 A The best of my recollection, yes. 7 Q And that Dow was also making 2,4-D? 8 A Yes. 9 MR. PIERCE: Objection to the form of the 10 question, if that is a question. 11 MR. DAVIS: Let's do one thing for the judge 12 right now which is I think I'm entitled to ask leading 13 questions here. It's a witness who has been an 14 employee of The Dow Chemical Company, now works for Dow 15 Corning. If your objections are to leading then they 16 have no foundation. 17 MR. PIERCE: I*am also objecting to the form 18 of the question and that last one in particular was not 19 even a question. 20 Q You're aware that Dow made Agent Orange during the Viet 21 Nam war? 22 A No, sir. 23 MR. PIERCE: Objection to the form. 24 Q You are aware today of that, aren't you? 25 A What I think I know is they made ingredients for it. I GENERAL REPORTING SERVICE, INC. 2338 9 1 never heard the term until long after. 2 Q Dow's 2,4,5-T and Dow's 2,4-D were blended to make 3 Agent Orange as far as you know? 4 MR. PIERCE: Objection to the form of the 5 question. Not only leading, but argumentative. The 6 man has answered as to his knowledge. 7 MR. DAVIS: It's going to be a long day, Stan. 8 MR. PIERCE: it is. 9 Q Let's talk about your involvement with the 10 trichlorophenol plant at the Dow Midland plant. What 11 was the 199 Building? 12 MR. PIERCE: Objection to the form. Want to 13 give us a time frame? 14 Q Do you know what the 199 Building was, Mr. Silverstein? 15 A Yes, sir. 16 Q What was done there? 17 MR. PIERCE: Objection to the form. 18 A I'm sorry. Two major products were made there. 19 Q What were those? 20 A Aniline and trichlorophenol. 21 Q And at the time that you became involved with the 199 22 Building trichlorophenol was being made there, right? 23 A Yes. 24 Q And was this in approximately 1964 when you first 25 became involved in the production of trichlorophenol? GENERAL REPORTING SERVICE, INC. 2339 > O awac. 10 MR. PIERCE: Objection to the fora of the question. The witness has not indicated he was involved in the production of trichlorophenol. Q You were involved in the trichlorophenol production unit, is that correct, not that you produced it yourself but that you had some involvement as an industrial hygienist, correct? A Yes, sir. Q And that began in 1964? A To the best of my recollection, yes. Q I want to show you a memorandum or a letter and let me just go ahead and have this marked as Exhibit 1. (DepX#l marked.) Q What we have is a memorandum from Ray Holmes to Mr. H. R. Hoyle on Dow stationery dated July 30th, 1964, with some writing at the top of it and Mr. Silverstein, if I can ask you if the writing at the top indicates that you were familiar with this memo at the time. You may review it. You had this in your possession back in 1964? A I don't remember for sure that it was in my possession. Q Your name is indicated at the top of this memo, isn't it, in handwriting? A It looks like mine. MR. PIERCE: Where is that? I'm sorry. Mr. GENERAL REPORTING SERVICE, INC. 2340 0-3^3^ 11 1 Davis, if you could show me. 2 Q Just so that the record's clear, on Exhibit 1 the 3 handwriting at the top looks to me like it says Larry 4 on the left-hand side. You were known by Larry, were 5 you not? 6 A Yes, sir. 7 Q And then it says: "Alex, please return this to me. 8 Larry S.M Is that the way you read this? 9 A Yes, sir. 10 Q And you're Larry S ., is that right? 11 MR. PIERCE: Objection to the form. 12 Q You presume that this was yours, is that correct? 13 MR. PIERCE: Why should he presume it's his? 14 He gave you the answer to your question. But go ahead 15 and answer it. 16 MR. DAVIS: He did until you suggested 17 otherwise. 18 A Is there a question? 19 Q The question you have already answered, I was just 20 responding to Mr. Pierce's question about what this 21 said. 22 A Okay. 23 Q In the 199 Building Dow made trichlorophenol by using 24 tetrachlorobenzene, methanol and caustic, is that 25 correct? GENERAL REPORTING SERVICE, INC. 2341 0'aH3 12 1 MR. PIERCE: I just like to indicate that 2 certainly the witness is not an expert on production 3 but go ahead and answer to the best of your ability. 4 Q That was your understanding of how the process worked, 5 correct? 6 A To my recollection, yes, sir. 7 Q Okay. And you can refresh your memory with Exhibit 1 8 if you care to at any time. Do you recall that in the 9 production of trichlorophenol in this Building 199 that 10 there was a -- an oil material from the trichlorophenol 11 reactor which was called a caustic insoluble oil? Do 12 you recall that? 13 A I remember the term, yes. 14 Q Do you know if it was also called a non-saponifiable 15 fraction? 16 A That doesn't strike a note of familiarity, no. 17 Q What was this oil that -- what was your understanding 18 about how this oil originated from the trichlorophenol 19 production process? 20 MR. PIERCE: His understanding as he sits 21 here? 22 MR. DAVIS: Yes. 23 A It was a waste stream from the process that was my 24 knowledge, my understanding. 25 Q And do you remember what Dow would do with this oil GENERAL REPORTING SERVICE, INC. 23p4. a2H 13 1 would be to separate it in the 199 Building from the 2 trichlorophenol product and incinerate it? 3 MR. PIERCE: Objection to the form of the 4 question. It's compound, it's leading. 5 Q You recall that, don't you, Mr. Silverstein? 6 A Would you give me the question part of that, please? 7 Q Okay. Dow would take this oil in the 199 Building 8 that was part of the trichlorophenol product and would 9 separate the oil and incinerate it? You recall that, 10 don't you? 11 MR. PIERCE: Continue the objection. 12 A I'm not sure I hear a question. Are you asking me to 13 verify that? 14 Q I'm asking you if that statement is a correct 15 statement? % 16 A I don't know for sure. 17 Q Have you reviewed Exhibit 1? Would you disagree with 18 the statement in Exhibit 1 that the oil was separated 19 and incinerated? 20 MR. PIERCE: Wait. Mr. Davis, let's have a 21 clarification. You indicated to the witness before he 22 could use the document to refresh his recollection. 23 Are you now asking him if the document 24 refreshes his recollection or if he's going to argue 25 that the language in the document speaks -- which GENERAL REPORTING SERVICE, INC. 2343 14 1 speaks for itself says otherwise? I mean I don't 2 understand what you are really asking this witness to 3 do. 4 Q If you don't recall you may use Exhibit 1 to refresh 5 your recollection. 6 HR. PIERCE: If it can do that. % 7 Q Please -- 8 A I didn't read it all because part of it is very 9 difficult to read and I just didn't want to take the 10 time but if you want me to I will read it, okay? 11 Q I appreciate it. 12 A Some of it is still illegible but I have read it. 13 Q All right. Does it refresh your recollection about the 14 caustic insoluble oil fraction from the trichlorophenol 15 process? 16 A Yes, I guess. 17 Q And you now remember that it was incinerated and -- % 18 separated from the trichlorophenol and incinerated? 19 MR. PIERCE: Objection to the form of the 20 question. 21 A That was my understanding at the time, yes, sir. 22 Q And this memo in Exhibit 1 also talks about a chloracne 23 incident in 1964, is that correct? 24 MR. PIERCE: The document speaks for itself. 25 Q You remember that incident, don't you? GENERAL REPORTING SERVICE, INC. 2344 V- -`-H1 ... ..'is.. 1 A Yes, sir. 2 Q And you recall that the Dow trichlorophenol plant 3 was pushing production in 1963 and that's what led to 4 the chloracne incident in '64? 5 HR. PIERCE: I believe that the witness has 6 already testified he was not involved in 1963. 7 Q Do you recall from reading this memo, and I can show 8 you some other documents if need be to refresh your 9 recollection? 10 MR. PIERCE: Objection to the form of the 11 question. 12 Q Do you recall that? 13 A I'd like to know what the question is again, you know. 14 Q It's unfortunate but we keep losing the question after 15 all the objections. But we'll try to persevere. You 16 do recall that the chloracne incident in '64 was as a 17 result of Dow pushing production in '63 and some 18 process changes that occurred? 19 MR. PIERCE: Objection to the form of the 20 question. 21 A My recollection is the process changes were believed to 22 have contributed to the thing, yes. 23 Q Okay. And you know that pushing production to the 24 limit had something to do with it as well? 25 MR. PIERCE: Objection. Asked and answered. GENERAL REPORTING SERVICE, INC. 2345 1 A No, I don't Jcnow that. 2 Q The chloracne was first noticed in approximately 3 January or February of 1964, do you recall that? 4 HR. PIERCE: Objection to the form. 5 A I read it in the memo. Hy recollection was it was 6 later than that but that shows how memory goes. 7 HR. DAVIS: Let me go ahead and introduce 8 Exhibit 2. Let's mark this. 9 (DepX#2 marked*.) 10 MR. DAVIS: You want to look at it? 11 MR. PIERCE: Sure. Gary, there appear to be 12 two documents clipped together. You want to take a 13 look and make sure? I don't know if that's the way 14 you want it or -- 15 MR. DAVIS: Let me just state for the record 16 that what we have is a document, Exhibit 2, which is 17 entitled "The Chloracne Problem, Biochem's 18 Contribution", dated 3-11-65. 19 MR. PIERCE: I just want to point out you 20 seem to have Exhibit 1 attached to it as well. 21 MR. DAVIS: That is correct. I kept that 22 attached since they were in that form when we got the 23 documents and the Dow Bates stamp numbers are 24 consecutive among these. So let me just show this to 25 Mr. Silverstein. GENERAL REPORTING SERVICE, INC. 2346 0-M43 17 1 MR. PIERCE: All right. And then there 2 appears to be yet another document after Exhibit 1. is 3 that in the form that you wish to present it to us? 4 MR. DAVIS: That is correct. That appears to 5 be the form in which this document was copied. 6 Q Mr. Silverstein, have you ever seen Exhibit 2 before? 7 A It looks like something I have seen before, yes, sir. 8 Q You're the author of the first part of Exhibit 2, the 9 document entitled "The Chloracne Problem", is that 10 correct? 11 MR. PIERCE: Objection to the form. I think 12 it's really confusing. But go ahead. 13 Q You're the author of this document? 14 MR. PIERCE: By "this document", what do you 15 mean? 16 MR. DAVIS: I one I just described that says 17 "The Chloracne Problem, Biochem's Contribution", dated 18 3-11 '65. 19 Q You're the author of that, is that correct? 20 MR. PIERCE: Just to clarify, you don't mean 21 the entire exhibit,m is that correct? 22 MR. DAVIS: I thought we made that clear. 23 MR. PIERCE: Okay. 24 A It looks like something I remember writing but I can't 25 verify it's accurate because I did not read every word GENERAL REPORTING SERVICE, INC. 2347 ` O- 18 1 and I couldn't remember it anyway if I had after 25 2 years. 3 Q I understand it's been a long time. Did you review any 4 documents in preparation for this deposition? 5 A No, sir. 6 Q Okay. Well, I'm going to give you an opportunity to 7 review Exhibit 2 for a few minutes and see if it 8 refreshes your recollection about some things, okay? 9 A I will need a few minutes to read through it because 10 again I did not look at every word. 11 I would like to request a restroom break. 12 MR. DAVIS: Certainly. 13 (DepX#3 through DepX#21 marked.) 14 (Recess) 15 MR. DAVIS: Let's go back on the record. 16 Q (By Mr. Davis, continuing): Mr. Silverstein, I learned 17 how to pronounce your name correctly during the break. 18 I apologize. 19 Have you had an opportunity to review Exhibit 2? 20 A Yes, sir. 21 Q Okay. And you once again were the author of Exhibit 2? 22 MR. PIERCE: Objection to the form. There are 23 three, at least three different documents. 24 Q Let's clarify that now for the record. Let me just 25 have your copy of Exhibit 2. I am going to take what GENERAL REPORTING SERVICE, INC. 2348 19 is attached to Exhibit 2 and I am going to pull it off and can you verify first of all that the first document attached to Exhibit 2 is a copy of what has already 4 been marked as Exhibit 1? 5 A This is versus that? 6 MR. PIERCE: The document speaks for itself. 7 Q Is that the same document as Exhibit 1? 8 A It appears to be. 9 Q Okay. 10 A Without reading word for word. 11 Q That's all I need. Let me mark this as Exhibit 2-A 12 which is another document that was attached to Exhibit 13 2. 14 (DepX#2-A markfed.) 15 Q Exhibit 2-A is titled "Chloracne Status Report - July 16 to September, 1964", from A. F. Lueck -- is that how 17 you say it? 18 A Yes, sir. 19 Q L-u-e-c-k. September 28th, 1964. We'll just leave 20 that with you. Right now let me ask you first of all 21 about Exhibit 2. What was biochem that's referred to? 22 A It was the biochemical research laboratory of The Dow 23 Chemical Company. 24 Q Okay. Is that where you worked? 25 A Yes, sir, initially. GENERAL REPORTING SERVICE, INC. 2349 O ' Z H '-t'f 20 1 Q Okay. And after reviewing Exhibit 2 do you recall that i 2 the chloracne that we have talked about that occurred 3 in the 199 Building was mostly due to exposure to the 4 caustic insoluble oils? 5 MR. PIERCE: Objection to the form. 6 A It was the primary source as I recall it, yes. 7 Q Okay. If you can maybe speak up a little bit? 8 A Oh, yes. I'm sorry. I'll try better. 9 Q And -- 10 A Or try harder. 11 Q What do you recall about how that chloracne looked in 12 the workers who worked in the plant, in the 199 13 Building? 14 MR. PIERCE: Objection to the form. 15 A Visual appearance? 16 Q Yes. % 17 A Blackheads like teen-ageacne. 18 Q How many workers suffered from chloracne at that time? 19 MR. PIERCE: Objection to the form. 20 A I don't remember other than what's in the document. 21 Somewhere in the 40 range, I think. 22 Q Okay. Now, Dow had had experience with chloracne 23 before, is that right, before 1964? 24 A I was told that, yes. 25 Q And Dow knew that certain chlorinated organic compounds GENERAL REPORTING SERVICE, INC. 2350 p S.hM'7 21 1 caused chloracne as early as 1941? 2 MR. PIERCE: Objection to the form. 3 A I know that only from being told or reading, yes. 4 Q And you wrote that in your memo on page 3, is that 5 correct, of Exhibit 2? 6 A Would you restate the question? I lost track of it. 7 Q Okay. The question was Dow knew as early as 1941 that 8 certain chlorinated organic compounds caused chloracne? 9 MR. PIERCE: Are you asking him does he recall 10 that now or ~ 11 MR. DAVIS: That was my first question and he 12 said he was told that and I said and you wrote that in 13 your memo, particularly concerning the V. K. Rowe paper 14 that's mentioned in here. 15 MR. PIERCE: Objection. 16 A Sorry. Well, that paper as I remember it described a 17 test but I do not recall what compounds were involved 18 in the test to be honest with you, sir. 19 Q Okay. Fair enough. This test that you're referring 20 to was a test that was reported by Adams, Irish, 21 Spencer and Rowe in 1941 which was a test on rabbit 22 ears, is that right? 23 A That is true. 24 Q And describe how that test worked, if you recall? 25 MR. PIERCE: How that test worked in 1941? ' GENERAL REPORTING SERVICE, INC. 2351 D 22 1 HR. DAVIS: Or any time that it was used. 2 A I'm not a toxicologist but I will describe my 3 understanding of the test, okay? 4 Q Okay. 5 A The test material was applied to the inner ear of a 6 rabbit and after a period of time, minimum 7 days as I 7 remember being told, the follicles of the ear either 8 did or did not appear more prominent than normal. And 9 this was an indication of something in the test 10 material that could produce the folliculitis on the 11 animal's ear and that was the basis or the extent of 12 the test actually. 13 Q By folliculitis you mean a skin reaction, is that what 14 you were looking for? 15 A The hair follicles inside the rabbit's ear where the 16 material had been placed were affected, yes. 17 Q And you also recall, don't you, that a Dow lab 18 researcher in 1944 had experienced chloracne and had at 19 least tentatively identified the type of compound that 20 could cause chloracne? i 21 MR. PIERCE: Objection to the form of the ! 22 question. 23 A I don't remember his having chloracne but apparently he 24 did find some materials and I don't know what they 25 were, as indicated on page 3. GENERAL REPORTING SERVICE, INC. 2352 23 1 Q Let me ask you if you have ever seen Exhibit 4 before 2 which ve have previously marked. 3 MR. PIERCE: I just like to indicate that the 4 first page is at least to me illegible but -- 5 Q Appears to be a -- some sort of handwritten notes from 6 a laboratory and if you can -- if the first page is 7 unreadable please look at the rest? 8 MR. PIERCE: Let me just object to the 9 characterization but please, go ahead and read it. 10 A I have never seen this before, sir. 11 Q Okay. Where did you get the information about the 1944 12 research that's reported on Exhibit 3 of -- I'm sorry, 13 page 3 of Exhibit 2? 14 A From Dow employees at the time who were still active. 15 Q In around 1945 -- 1944 or '45 Dow first tested the 16 caustic insoluble oil portion of the trichlorophenol 17 production on rabbit ears, you recall that? 18 MR. PIERCE: Objection to the form. 19 A I was told that and I was not with Dow at the time. 20 Q okay. And you've -- strike that. 21 A I can hear you from here, sir, if you want to keep 22 going. 23 A I don't think she can hear your answers. 24 MR. PIERCE: What do you need, this one? 25 MR. DAVIS: Yes. GENERAL REPORTING SERVICE, INC. 2353 ) S W S O 24 1 Q And you recall Dow knowi* ng in 1955 that the Germans had 2 had problems with chloracne in the production of 3 trichlorophenol? 4 HR. PIERCE: Objection to the form of the 5 question. 6 A I don't recall it that early, no. 7 Q You have written that in Exhibit 2, correct, on page 4? 8 A What appears to be my document, I did write it, but I 9 don't recall it. 10 Q And the Germans actually identified the compound as 11 being the compound responsible for chloracne as being 12 the tetrachlorodibenzodioxin, is that correct? % 13 MR. PIERCE: Objection to the form and the 14 witness has already testified he has no recall. 1 5 A What I recall is they proposed that this may be it. 16 They hadn't identified it. 17 Q This was around 1957? 18 A To the best -- 19 MR. PIERCE: Objection to the form of the 20 question. 21 Q You may answer. 22 A To the best of my recollection, yes. 23 Q And Dow had been taking precautions in handling those 24 caustic insoluble oils since 1945, is that right? 25 A That's what I was told. Remember, I wasn't there until GENERAL REPORTING SERVICE, INC. 2354 O' 25 1 '55. 2 Q That's right. Okay. But did you become involved in 3 the trichlorophenol building in 1957 when Dow was 4 looking at the caustic insoluble oils? 5 MR. PIERCE: Objection to the form of the 6 question. 7 A Not to my recollection, no. 8 Q Okay. So did someone tell you that Dow was looking at 9 the caustic insoluble oils for chloracne potential in 10 1957? 11 A Yes. Long after the fact,"yes. 12 Q Let me go ahead and ask you to look at what's been 13 marked as Exhibit 5 and let's just -- since you have 14 the document right now, if you'll please read the title 15 of the document first? 16 A "Chloracne in the Dow Trichlorophenol Plant Circa 1964". 17 Q And what's the date of this document? 18 MR. PIERCE: If you know the date. 19 A In the upper right corner, 2-24-76. 20 Q Are you the author of what's been marked as Exhibit 5? 21 A I did dictate a document and it looks like the one, 22 yes. I can't verify every word, of course. 23 Q Why did you dictate Exhibit 5? 24 A Why? 25 Q Yes. What was the purpose of this document? GENERAL REPORTING SERVICE, INC. 2355 Q.3.4^2- 26 A I honestly do not recall. I have been trying. Q Okay. Can I ask you the same question about Exhibit 2, 3 do you recall why you wrote it? 4 A The same answer, I do not recall to be honest. 5 Q Once the chloracne outbreak occurred in 1964 in the 6 trichlorophenol building at Dow, Dow determined that 7 the compound likely responsible was 8 tetrachlorodibenzodioxin, correct? 9 MR. PIERCE: Objection to the form of the 10 question. 11 A And the question's a bit vague because there are more 12 than one such material. 13 Q Okay. 14 A And I don't think I know what you're really asking. 15 Q Let's try to be as precise as we can then and maybe we 16 can use a shorthand notation as well. What I'm 17 referring to is the tetrachlorodibenzo-para-dioxin 18 which is often called TCBD and if we can just refer to 19 it as TCBD, would you be agreeable to that? 20 A I guess so. I have used it before. 21 Q Okay. Now, did Dow determine that TCBD was the 22 contaminant in the trichlorophenol process that was 23 responsible for the chloracne outbreak in Building 199 24 in 1964? 25 MR. PIERCE: Objection to the form of the % GENERAL REPORTING SERVICE, INC. 2356 D - 9-453 27 1 question. 2 A My recollection is we determined it was the primary 3 culprit. 4 Q Okay. And do you also recall that Dow tested TCBD and 5 found that it was the most potent chemical ever tested 6 in its toxicological lab oratory? 7 MS. JONES: Object to that question. 8 MR. PIERCE: Objection. This is outside this 9 witness's scope of knowledge. But go ahead and answer 10 it to the best of your ability. 11 A Once again I'm not a toxicologist but I did hear that, 12 certainly. 13 Q And if you'll please turn to Exhibit 5, page 8. You 14 also wrote that on page 8 of Exhibit 5, correct? 15 MS. JONES: Gary, could you tell me what 16 Exhibit 5 is? 17 MR. DAVIS: Sure. Off the record. 18 (Conference off the record.) 19 A I don't see that statement on page 8. 20 Q I'm sorry, I misspoke. It was on page 9. 21 MR. PIERCE: I'd just like to object in that 22 the document speaks for itself. If it says that it 23 does. 24 And could we have the question read back, please? 25 (Requested portion read back.) -GENERAL REPORTING SERVICE, INC. 2357 28 1 MR. PIERCE: I'd like to object to the 2 characterization of what the document states. I think 3 it is taken out of context and further that the document 4 speaks for itself. 5 Q Okay. You may answer the question about whether you 6 wrote that in Exhibit 5? 7 A It appears that I did, yes. 8 Q Okay. What -- how did your involvement start in 9 Building 199 with the trichlorophenol where the 10 trichlorophenol process was, do you recall that? 11 A My recollection is that I was told there was a problem 12 there and that my assignment was to find out what 13 exposures the workers may have been receiving or to 14 look at the situation. 15 Q Were you appointed as a full-time safety person for 16 Building 199 in the trichlorophenol process? 17 A Not at that time. 18 MR. PIERCE: Objection to the form of the 19 question. 20 A Not at that time. 21 Q When were you appointed as such? 22 A Sometime later. I don't remember exactly. 23 Q Okay. What precautions were you aware of that Dow took to prevent exposure to workers from the compound that caused chloracne in the trichlorophenol process? GENERAL REPORTING SERVICE, INC. 2358 29 % 1 MR. PIERCE: In what time frame? 2 Q In any time frame. 3 MR. PIERCE: You mean now? 4 MS. JONES: I'd object to that question in 5 that it's overly broad. 6 Q I'll try to be more specific then. 7 A Please. 8 Q You're aware that in 1957 the Boehringer Company, a 9 German chemical manufacturing company, sent a letter to 10 Dow and all other known trichlorophenol manufacturers 11 on how to avoid generating the chemical that causes 12 chloracne in the trichlorophenol process? 13 MR. PIERCE: Object to the form of the 14 question and I believe that has been previously 15 answered. 16 A I have seen such a letter. 17 Q Let me show you Exhibit 6 which has been previously 18 marked and ask if this is the letter? 19 MR. PIERCE: What do you mean by is this the 20 letter? 21 MR. DAVIS : The letter he just referred to. 22 MR. PIERCE: Are you asking him if he has seen 23 this letter? 24 MR. DAVIS : He just said he did. 25 MS. JONES: Gary, could I ask you guys since I GENERAL REPORTING SERVICE, INC. 2359 V-SH5<o 30 1 can't see the document, when you refer to an exhibit 2 give me the date of the exhibit and something that will 3 identify it. 4 MR. DAVIS: We will do that. 5 MS. JONES: Thanks. 6 MR. PIERCE: LeeAnn, this is a document dated 7 February 11th, 1967 -- 8 MR. DAVIS: '57. 9 MR. PIERCE: '57, which purports to be a 10 letter from -- signed Weyland, W-e-y-l-a-n-d, and it is 11 apparently addressed to The Dow Chemical Company. 12 MS. JONES: Thanks. 13 Q Mr. Silverstein, this is the letter from the German 14 chemical company Boehringer that you saw before 15 relating to measures to prevent chloracne? 16 MR. PIERCE: Objection to the form. I think 17 it's a mischaracterization of his previous testimony. 18 But answer it if you have seen it before. 19 A This appears to be an extremely poor copy of a letter I 20 remember but I can not speak to the -- you know, each 21 and every word. I can't even read them. 22 Q It is a poor copy, I will agree. One of the items that 23 Dow was aware of as a result of this letter is that the 24 temperature of the trichlorophenol process was 25 important in preventing the generation of the compound GENERAL REPORTING SERVICE, INC. 2360 D - 4 57 21 1 that causes chloracne, right? 2 MR. PIERCE: Are you asking him in terms of 3 awareness of The Dow Chemical Company or are you asking 4 him that's what the letter speaks to? I mean I object 5 to the question but answer it to the best of your 6 ability. 7 A I really don't know what the question is here. Would 8 you please rephrase it? 9 Q As a result of this letter which has been marked as 10 Exhibit 6, was Dow aware that the temperature of the 11 trichlorophenol reaction was an important factor in 12 preventing the generation of the chemical that causes 13 chloracne? % 14 MR. PIERCE: Objection to the form. I don't 15 think this witness is qualified to answer as to Dow's 16 awareness or to the basis of Dow's awareness, but you 17 can answer the question the best you can. 18 A Please understand I'm not a chemical engineer or a 19 process engineer and I certainly can't speak to Dow 20 Chemical Company's awareness. The letter mentions a 21 temperature in the content and that's all I can really 22 speak to with accuracy at this point. 23 Q Okay. That temperature was 150 degrees Centigrade? MR. PIERCE: You mean that's what the letter says? GENERAL REPORTING SERVICE, INC. 2361 32 1 MR. DAVIS: Yes. In Exhibit 6. 2 MR. PIERCE: Well, of course I object that the 3 letter speaks for itself but go ahead and take a look 4 at it. 5 Q Actually that night have been marked out of this 6 letter. Back in Exhibit 2 on page 8, which is right 7 here -- 8 A Page, sir? 9 Q 8, please. 10 A Page 8. Yes, sir. 11 Q 150 degreesCentigrade is the temperature that was 12 emphasized by the German chemical company Boehringer as 13 being a necessary temperature to minimize the threat of 14 chloracne? 15 MR. PIERCE: Are you asking the witness if 16 that's his present recall or if something to that 17 effect is written on page 8 of the exhibit? 18 Q Do you recall that at present? 19 A In all candor I recall it and page 8 confirms that that 20 was the number. 21 Q Okay. Now, what were some of the process changes that 22 were made at Building 199 where the trichlorophenol was 23 made in 1964 to prevent a recurrence of chloracne among 24 the workers? 25 MR. PIERCE: Objection to the form and it's GENERAL REPORTING SERVICE, INC. 2362 33 1 outside this person's scope of knowledge but you can 2 answer it to the best of your ability. 3 Q If you recall. 4 A From my standpoint as an industrial hygienist basically 5 the process was even closed more so than previously, 6 leak points, process equipment primarily were tightened 7 up or replaced in order to minimize leakage and a 8 couple of procedural changes to avoid sample taking 9 which was a potential exposure point. 10 Q And this was particularly with regard to the caustic 1 insoluble oils? 12 A No, sir. % 13 Q What about the -- was there something called a decanter 14 in the process that you recall where the caustic 15 insoluble oils would be drawn off? 16 A I recall that and I said no, sir a moment ago because 17 it wasn't aimed only at the caustic oil. 18 Q Okay. Let me ask you to look at what's been marked as 19 Exhibit 3. 20 MR. PIERCE: Gary, I think the witness has 21 already indicated that he is certainly not the person 22 expert in the process but for whatever you want to use 23 that for, please. 24 A Okay. 25 Q My question is does this look from your memory like it GENERAL REPORTING SERVICE, INC. 2363 D'SWi> 34 1 was the Dow process in u*se at that time in 1964-65? 2 HR. PIERCE: You mean is this document the 3 Dow process, number 3? 4 Q Is this a drawing that represents the Dow process? 5 A I don't remember ever seeing that drawing before and at 6 this late date I couldn't say that it even remotely 7 resembled it to be honest with you. 8 Q Okay. That's fine. The purpose of the changes in the 9 trichlorophenol process were to minimize the worker 10 exposure to the compound that could cause chloracne, is 11 that right? 12 A Yes, sir. % 13 Q And at that point in time in 1964 when you got involved 14 did you cause some rabbit ear tests to be made of the 15 caustic insoluble oils from the trichlorophenol 16 process? 17 MR. PIERCE: Objection to the form and the use 18 of the term "caustic insoluble oils". 19 A In conjunction with my industrial hygiene efforts a 20 n u m b er of tests were run on many different things, yes. 21 Q Were some of those run on the caustic insoluble 22 oils? 23 A As I recall, yes. 24 Q And what happened to the rabbits that were tested with 25 those oils in 1964? GENERAL REPORTING SERVICE, INC. 2364 35 1 HR. PIERCE: I'm sorry, but that's not a clear 2 question, honestly. 3 Q Was the concentration of the chemical that caused the 4 chloracne in the caustic insoluble oils so high in 5 1964 that the rabbits tested for the rabbit ear test 6 died? 7 HR. PIERCE: Objection to the form of the 8 question. 9 A To my recollection there was an instance in which that 10 happened, yes. 11 Q Did Dow consider shutting down the Building 199 process 12 in the 1964 time frame? 13 A To the best of my recollection it was considered, yes. 14 Q And sometime in the 1964 or '65 time frame you were 15 appointed full-time safety officer for that plant? 16 A Yes, sir. 17 Q Were wipe samples taken around the buildings that 18 were responsible for the production of 19 trichlorophenol? 20 A Yes, sir. 21 Q What were wipe samples, can you describe those? 22 A A wipe sample is a technique adapted from radiation 23 safety of simply wiping a surface with a filter paper 24 or absorbent paper and subsequently analyzing the paper 25 for the material being tested for. GENERAL REPORTING SERVICE, INC. 2365 O-a-Wfc V- 36 1 Q Okay. And describe how that was done in the 2 trichlorophenol process? What kinds of surfaces would 3 you sample? 4 MR. PIERCE: Objection to the form. Could we 5 have a time frame here? 6 Q In the 1964-65 time frame. 7 A Primarily work surfaces that might be contacted by 8 employees. They were the focal point of the wipe test. 9 Q What would you then do with the filter paper or paper 10 that was used to wipe the surface, how would you test 11 it? 12 A I didn't personally tesp them, sir. 13 Q Do you know how they were tested though? 14 A Yes. In the beginning they were submitted to 15 toxicology for the animal test that's been previously 16 discussed. 17 Q The rabbit ear test? 18 A Yes. 19 Q And was there -- at a later time frame was there 20 another type of test done on those wipe samples? 21 A Eventually in a machine. An analytical method was 22 developed and used. 23 Q And was the purpose of the wipe test to determine the 24 levels of TCBD or dioxin on surfaces in the plant? 25 MR. PIERCE: Objection to the form of the GENERAL REPORTING SERVICE, INC. 2366 Q-9b3 37 1 question. 2 A Well, the rabbit ear test didn't identify materials, 3 just said whether there was a material that was capable 4 of causing a response. When the analytical method came 5 along we were able to identify the specific material we 6 were looking for, yes. 7 Q And the rabbit ear test was even more sensitive than 8 the analytical method that came along in determining 9 whether there was a material present that caused 10 chloracne, is that right? 11 A Initially, yes. I don't know what the situation is 12 now. 13 Q What did you find when you took those wipe samples and 14 had them analyzed in 1964? 15 A Well, that's a very broad question. I found all kinds 16 of results, you know, good and bad. 17 Q Did you find that the Building 199 was extensively 18 contaminated with the compound that causes chloracne? 19 MR. PIERCE: Objection to the form of the 20 question. Objection to the use of the term 21 "extensively" which has no definition. 22 Q You may answer. 23 A To my best recollection early on I found positive 24 samples in the 199 Building. 25 Q If you will turn to page 9 of Exhibit 2, please. And % GENERAL REPORTING SERVICE, INC. 2367 38 1 towards the middle of the page you stated that the 2 building was found to be extensively contaminated, is 3 that right? % 4 A The statement is there, yes. 5 Q And what did you do once you found that contamination 6 or what did you request to be done with regard to 7 removing that contamination from the building? 8 A I reported it to the, you know, responsible people and 9 recommended that clean-up be done promptly and to my 10 recollection it was done quite promptly. 11 Q How was the building cleaned? 12 A Oh, basically by high pressure water hose treatment. 13 That's my recollection. 14 Q Okay. Were there workers wiping the surfaces at the 15 same time or -- 16 MR. PIERCE: Objection to the form of the 17 question. 18 A If you are indicating wipe testing, no. 19 Q No, I mean in terms of the actual cleaning, was it by 20 hand or was it just the water hose? 21 A Wow, I honestly don't remember. 22 Q Let me show you two documents that have been previously 23 marked as Exhibits 7 and 8 and take a few minutes to 24 review those, please. 25 MR. DAVIS: Off the record. GENERAL REPORTING SERVICE, INC. 2368 1 (Recess) 2 MR. PIERCE: Okay. I believe the witness 3 has completed his review. 4Q (By Mr. Davis, continuing): What I want to ask you 5 first about Exhibits 7 and 8, Mr. Silverstein, is are 6 these Dow documents that describe the steps to be taken 7 to eliminate exposure to the chloracnegen in Building 8 199 or the trichlorophenol process? 9 MR. PIERCE: Objection to the vagueness of the 10 question and the characterization of the documents. 11 Q You may answer. 12 A They appear to be such documents but I don't recall 13 them. 14 Q Do they refresh your recollection in any way on the 15 steps that were taken in 1964 and '65? 16 A In a general way a number of the steps come through as 17 familiar because of my involvement but on specifics, 18 no. 19 MR. DAVIS: Let me see those. 20 MR. PIERCE: Sure. 21 Q Let's just go ahead and identify these for the record. 22 Exhibit 7 is entitled "Analine Section, Equipment" and 23 then it says "TCP Chloracne Completed Changes November 24 13th, 1964". 25 Item 12 on page 1 of Exhibit 7 discusses -- or GENERAL REPORTING SERVICE, INC. 2369 D ` ip (o 40 1 I'll read the statement and let me ask you a question 2 about it. It says: "November 13th - Reactor room 100 3 feet by 180 feet washed down with detergent and painted 4 with aluminum." 5 Is that the clean-up that you were describing? 6 HR. PIERCE: Objection to the form that you 7 are reading from a document not identified. But go 8 ahead and answer the question. 9 A I don't believe so, no, it doesn't sound like it. 10 Q Do you recall what that item would have referred to? 11 A I have no recollection of that specific item, no. 12 Q What is the reactor room? Does that ring a bell to 13 you? 14 A I believe we referred to the enclosure of the process 15 equipment as the reactor room but that was an addition 16 to minimize exposure. 17 Q When you say the reactor, you mean the trichlorophenol 18 reactor? 19 MR. PIERCE: Objection to the form. 20 A I believe so. 21 Q What hygiene precautions did you recommend that the 22 workers take to minimize chloracne and to minimize 23 their exposure to TCBD or dioxin? 24 MR. PIERCE: Objection to the form of the 25 question. You may answer. GENERAL REPORTING SERVICE, INC. 2370 D-^^1 ......... .... 41."....... .. .-- ....... 1 A Okay. Strictly from memory, the basic precautions 2 were to use skin protection, namely gloves for routine, 3 and full suits when anything more in the way of 4 possible exposure might occur. And in addition extreme 5 personal hygiene in terms of washing thoroughly after 6 any possible contact, even with the protection, and 7 showers frequently, required beginning and end of a 8 shift and required any time a person had to get into a % 9 full suit -- that's immediately after the job, excuse 10 me. 11 Q So you required showers twice a day -- 12 HR. PIERCE: Objection to the form. 13 Q -- for the workers that worked with trichlorophenol? 14 MR. PIERCE: That is not -- that's a 15 mischaracterization of what he just indicated to you. 16 Q I am asking another question. You required showers 17 twice a day for the workers that worked with 18 trichlorophenol? 19 MR. PIERCE: Objection to the form. I think -- 20 well, go ahead. I'm sorry. 21 A Again to the best of my recollection at least at lunch 22 break and end of their shift, twice a day, and any time 23 they took a smoke break or otherwise, if they had had 24 any reason to get into the full protective equipment. 25 Q Let me show you what's been marked as Exhibit 10 and GENERAL REPORTING SERVICE, INC. 2371 42 1 I'll go ahead and -read iBHe tliillgi cod' it- "Safety 2 Precautions For Trichlaarcphenal Operators, I*. <E- % 3 Silverstein, October 9th* iSdW". 4 A Judas Priest. 5 Q This is a difficult one t mead,, it's a bad rxrpy I 6 realize. 7 A Boy, I can't read -- 8 MR. PIERCE: Gary* 3Let nne just indicafe that 9 the witness has indicated bo mre that he is having 10 substantial trouble in reading this and I thirik 11 especially in certain part s t"s almost illegible. 12 Q Just do the best that you coil. Hhe second page is a 13 little easier to xead. 14 A Okay. Let's try it. 15 Q Okay.Does that refresh y our recoTB(ection afemut the 16 showering, for instancs? 17 MR. PIERCE: Objection to the form. 18 A Not really because it's so illegaMLe19 Q You can read page 2, can't you? 20 A Yes. You're right, page 2 iis reasonablylegible and 21 you said refresh my memory and 1 think I remembered it 22 without this. 23 Q Also you recommended in ifcdhibit 1 that plastic booties 24 are worn whenever the c^wratorrs were stalking around in 25 the area of the trirrhloraphenol {production? GENERAL SEPQRTIENG .SEgVIta;, 3HSC- 2372 43 1 HR. PIERCE: If you are going to speak from 2 the document, please be specific as to the area and not 3 use generalities which the document does not contain. 4 Q What does the document tell you about the use of 5 plastic booties? 6 A All I can read with some assurance is plastic booties 7 must be worn -- illegible -- oil -- illegible -- the 8 stripper column I believe it says pumps. 9 Q Do you recall anything, having attempted to read that, 10 about where plastic booties were required? 11 A Again, from memory rather than this, we did require 12 plastic booties where there was a possibility of shoe 13 contamination, yes. 14 Q And this was to keep the workers from tracking the 15 dioxin -- 16 Off the record. 17 (Conference off the record.) 18 MR. DAVIS: Back on the record. 19 (Question read back.) 20 Q Okay. Out of the process area? 21 MR. PIERCE: Objection to the form. 22 A That's correct. 23 Q Did the workers at the Dow.trichlorophenol plant wear 24 their work shoes home? 25 MR. PIERCE: You mean in -- anywhere in the GENERAL REPORTING SERVICE, INC. 2373 D-sM'lo 44 plant? 2 Q In the trichlorophenol plant in the '64-65 time frame. 3 A After implementation of the added precautions the 4 answer is no. 5 Q You also provided boots for them to wear to work in 6 that time frame, is that right? 7 A In the process area, yes. 8 Q And did you provide double lockers for the workers in 9 the trichlorophenol process? 10 A Yes, sir. 11 Q Describe what a double locker is and why you would use 12 that? 13 A The term is used to describe two lockers assigned to a 14 given employee so that he can place his street clothes 15 in the locker called the clean locker, proceed to get 16 his work clothes out of the other locker and then go 17 into work. On leaving work he leaves his work clothes 18 in a locker and then proceeds through the shower to his 19 street clothes. 20 Q And is that to prevent his work clothes from 21 contaminating his street clothes? 22 MR. PIERCE: Objection to the form. 23 A Yes. 24 Q And did you also require the workers to shower after 25 dealing with the caustic insoluble oils in their GENERAL REPORTING SERVICE, INC. 237 4 D* / ...... 45........ ... ............... ...... .. 1 job? 2 A Yes, sir, after implementation of these controls. 3 MS. JONES: Mr. Silverstein, could I ask you 4 to speak up a little bit? 5 A I'm very sorry. I keep forgetting that you are relying 6 on the speaker. You're the only nice one here so I'll 7 try harder. 8 MS. JONES: Thank you. 9 Q Was the shower time for the -- let me strike that just 10 a minute. Mr. Silverstein, am I not being nice to you 11 in this deposition? 12 MR. PIERCE: I don't think he wants you to 13 answer that. 14 Q If any of my questions offend you, please let me know 15 and I'll try to rephrase them. 16 A I'm not taking itpersonally. 17 Q Was the shower and wash time for the employees who were 18 required to take two showers a day paid time? 19 A Yes, sir. 20 Q Is that important in encouraging the employees to 21 actually take those showers that you have required? 22 MR. PIERCE: Objection to the form of the 23 question. 24 A I believe so. 25 Q Were there alsodaily safety meetings in the / % GENERAL REPORTING SERVICE, INC. 2375 3,Q'L{7P-- 46 1 trichlorophenol process area, particularly at the time 2 when you were trying to implement these precautions? 3 A To the best of my recollection while I was health 4 officer the answer is yes. 5 Q How long were you health officer in that process? 6 MR. PIERCE: Objection to form of the 7 question. 8 A It was a matter of months, approaching a year the best 9 I can recall. 10 Q We were talking earlier about the analytical methods 11 for determining the presence of the dioxin or the 12 chloracnegen in process materials or in wipe samples. 13 We talked about the rabbit ear test. Are you familiar 14 with the other type of test that Dow implemented as an 15 analytical method for determining the presence of 16 dioxin or TCBD? 17 MR. PIERCE: Objection to the form. No 18 foundation. Go ahead and answer. 19 A I'm generally familiar with what was then called the 20 VPC method, vapor phase chromatography. 21 Q Is that sometimes also called a gas chromatograph? 22 A Yes. 23 Q And when was a method developed for analyzing for 24 dioxin or TCBD in the process materials from the 25 trichlorophenol process at Dow? GENERAL REPORTING SERVICE, INC. 2376 47 1 MR. PIERCE: Objection to the form of the 2 question. 3 A You asked when? 4 Q Yes. 5 A To the best of my recollection about 1965, I think. 6 Q Okay. Nov, was the method, that gas chromatograph or 7 the VPC method as you referred to it, capable of 8 detecting the dioxin in the caustic insoluble oil 9 fraction? 10 MR. PIERCE: You realize that the witness is 11 here in his capacity -- I assume you are asking him as 12 industrial hygienist. If you have a misconception that 13 he is an analytic chemist left me say he's not but to 14 the best of your knowledge give him an answer, please. 15 A Okay. As an industrial hygienist I need to know if a 16 method is sensitive enough to tell me amounts in 17 relation to what I want to control to. The answer to 18 your question is that initially, no. The GC method 19 wasn't sensitive enough. 20 Q But the GC method could detect the presence of dioxin 21 at some level in the caustic insoluble oils even in 22 1964, correct? 23 MR. PIERCE: If you know? 24 A Not to my knowledge. 25 Q I know it's been a long, long time since then and I'm GENERAL REPORTING SERVICE, INC. 2377 48 1 not trying to contradict your answer but I do want to 2 show you Exhibit 9 and see if this refreshes your 3 recollection. 4 A Okay. 5 Q Does Exhibit 9 refresh your recollection about the 6 analysis of the caustic insoluble oil fraction? 7 A I remember having seen such a document, yes. 8 Q Okay. And was the gas chromatograph analytical 9 procedure also used for testing trichlorophenol samples 10 for the presence of dioxin? 11 A Eventually in the time period, yes. 12 Q Okay. You recall that there were -- there was testing 13 of the trichlorophenol to determine whether it would 14 carry dioxin on into the 2,4,5-T product, don't you? 15 A I don't remember it that specifically. 16 Q Okay. Let me show you Exhibit 4 and let me go ahead 17 and note for the record what it is. That it's a memo 18 addressed to several people, including L. G. 19 Silverstein, dated May 4th, 1965, from Richard C. 20 Hoff, Quality Services Supervisor, Chemicals 21 Production Department, bn Dow stationery, regarding 22 "2,4,5-Trichlorophenol and 2,4,5-Trichlorophenoxyacetic 23 Acid Analysis for 2,3,7,8-Tetrachlorodibenzodioxin". 24 Does this refresh your recollection about the 25 analyses of the trichlorophenol for the presence of GENERAL REPORTING SERVICE, INC. 2378 D-a.W 49 1 dioxin as it was put forward in the process of making 2 2,4,5-T at Dow? 3 MR. PIERCE: Objection to the form and 4 objection to the perception that he required refreshing 5 as to the question you have now asked as opposed to the 6 question you previously asked. But in any event, 7 answer. 8 Q You may answer. 9 A My recollection is that we applied quality control to 10 the product for purposes of assuring no transfer of the 11 material from its production plant to anyplace. 12 Q Okay. So you tried to prevent the transfer of any 13 dioxin from the trichlorophenol plant to the production 14 of 2,4,5-T acid, that was one of the ~ 15 A That was one of the destinations, yes. 16 Q Then you tried to prevent the transfer ofdioxin from 17 the plant in the 2,4,5-T acid product? 18 MR. PIERCE: Objection to the form. 19 A Yes. 20 Q Using the gas chromatograph analysis? 21 A I believe so, yes. 22 Q Was it evident to you that the tars or oils from the 23 trichlorophenol process that were either by-products or 24 waste streams were where dioxin would accumulate? 25 MR. PIERCE: Objection to the question. GENERAL REPORTING SERVICE, INC. 2379 50 1 Compound, ambiguous, vague. Go ahead and answer. 2 A With the knowledge we had at the time we believed this 3 to be the case. 4 Q In the 1964-65 time frame? 5 A Yes, sir. 6 Q Did you ever determine anything that contradicted that? 7 A I'm not sure I understand the question. Sorry. 8 Q You said with the knowledge you had at the time you 9 believed that to be the case. Did you ever find out 10 anything differently? 11 A Wow. Well, we knew a lot beyond that, I believe is the 12 truth, you know, that it wasn't only in there. That % 13 was the primary. 14 Q Did you develop laboratory safety procedures for the 15 handling of dioxin in the laboratory? 16 A Yes, I did. 17 Q Let me show you Exhibit 12 and ask if these are those 18 procedures and let's off the record read this to 19 LeeAnn. 20 (Conference off the record.) 21 Q (By Mr. Davis, continuing): The document that was 22 just shown you is Exhibit 12. Is this the -- at least 23 one version of the safety procedures that you developed 24 for handling of dioxin in the laboratory? 25 A This appears to be a copy of procedures I wrote, yes, GENERAL REPORTING SERVICE, INC. 23>8a0n17 51 1 sir. 2 Q When did you first write those procedures? 3 A Latter part of the 1960's is my recollection. 4 Q Okay. Would you know whether or not Exhibit 12 is the 5 first written version or is it a subsequent draft? 6 A I wouldn't know for a fact which it is. 7 Q Okay. In Exhibit 12 you talked about the safe handling 8 of even small quantities of dioxin. Do you liken the 9 hazards of dioxin to the hazards of radioactive 10 materials? 11 MR. PIERCE: Objection to the form of the 12 question and the handling relates to laboratory and -- 13 go ahead and answer it to the best of your ability. 14 A Well, in the sense that precautions to be taken with 15 handling the material are very similar with those 16 taken handling radioactive materials will protect 17 people, yes. 18 Q Do you know who Exhibit 12 was sent to, if anyone? 19 A In my recollection it was sent to persons who requested 20 it from outside Dow Chemical or within, either. 21 Q You don't know of any particular persons who it was 22 sent to then? 23 A I do not recall any specific recipiants, no, sir. 24 Q Okay. Why would you recommend that persons using 25 dioxin in a laboratory throw away plastic gloves GENERAL REPORTING SERVICE, INC. 2381 0-^47^ 52 i 1 without contacting the exterior surfaces of the gloves? ! 2 MR. PIERCE: Are you referring now to the 3 document or -- 4 Q Yes. Referring to Exhibit 12. 5 A Because unless employees are instructed on a proper 6 method of removing contaminated gloves they unwittingly 7 may contact the contaminated outside. You have to ! 8 show them how to do it properly. 9 Q What type of gloves did you require the employees in 10 the trichlorophenol process to wear? 11 MR. PIERCE: Objection to the form. A 12 mischaracterization of his earlier testimony and by 13 using generalization as to the trichlorophenol process. 14 But go ahead and answer. 15 A The basic requirement was impervious and the actual 16 glove depended on the operation to the best of my 17 recollection. 18 Q What about the employees that were actually handling 19 the caustic insoluble oils in some fashion? 20 A Probably a specific rubber glove that we had in the 21 plant. 22 Q Did you ever require any of those employees to wear an 23 air hood when they were dealing with the caustic 24 insoluble oils? 25 A Yes. GENERAL REPORTING SERVICE, INC. 2382 53 1 Q What's an air hood? 2 A It's properly called an air-supplied hood and it is a 3 covering over the head with breathing air brought to 4 the hood either from an outside line of breathing air 5 or from a self-contained oxygen or air tank that the 6 person wears on the back. 7 Q What was the purpose of requiring such a breathing 8 hood? 9 A Because we didn't know if the person -- we didn't know 10 whether the person might be exposed to an airborne 11 material. 12 Q By the airborne material you mean the material that 13 caused the chloracne, the dioxin in the process? 14 MR. PIERCE: Objection to the form. Asked and 15 answered. 16 A That and other materials, yes. 17 Q What were the employees actually doing, what activity 18 were they performing where you required the air hood in 19 handling caustic insoluble oils? 20 MS. JONES: Objection if that's not limited to 21 any particular time period. 22 Q You may mention any time period you care to. 23 A Well, during the time period of the middle '60s when I 24 was health officer. My recollection is that in 25 relation to the oil the employees were required to wear GENERAL REPORTING SERVICE, INC. 2383 0-SWV6 54 1 the hood if they took a sample of the material or when 2 they filled the Dempster, the receptacle for the 3 material. 4 Q Okay. Do you recall what the employees would then do 5 with the Dempster, the material in the Dempster? 6 A It was carted away from the building. 7 Q And where did it go? 8 HR. PIERCE: If you know? 9 A It went to the Dow incinerator. I 10 Q Was that true during the whole time that you were the 11 safety officer in the trichlorophenol process? J 12 A Yes, to the best of my recollection. I 13 Q Why did you recommend in Exhibit 12 that clothing known j 14 to be contaminated should be disposed of with the j j15 precautions described under disposal of wastes? t 16 MR. PIERCE: Is that supposed to be a direct 17 quote from the document? 18 MR. DAVIS: That is a direct quote. 19 A May I read the entire part there? 2 0 Q Yes. 21 A I could only conjecture on why I stated it just that 22 way. Probably because most people weren't equipped or 23 wouldn't take the steps elaborated on in that same 24 section to assure that the laundry people and the 25 laundry equipment wasn't contaminated. GENERAL REPORTING SERVICE, INC. 2384 >3.4! 55 1 Q What steps would those have been? 2 MR. PIERCE: You want further conjecture? 3 MR. DAVIS: What he remembers. 4 A I think they are written in there. 5 Q Just from your memory? j 6 A From my memory it's basically assuring that people 7 transporting the contaminated laundry are protected by 8 having it inside clean bags -- clean on the outside. 9 That the people putting the clothing into the laundry 10 equipment are educated and trained to avoid touching 11 the stuff as it goes in', making any contact. And that 12 after the equipment -- after the materials have been 13 washed that the equipment itself is rinsed. 14 Q Okay. 15 MR. DAVIS: Let's take a short break. 16 (Recess) 17 Q (By Mr. Davis, continuing): Let's go back and let i 18 me ask you to look at what's been marked as Exhibit 21. ! j 19 It's very difficult to read. I apologize for the poor i| 20 copy. I just want to ask you to see if you can i 21 identify it. j 22 MR. DAVIS: Off the record. 23 (Conference off the record.) ii 24 Q If you can just attempt to review this document, Mr. 25 Silverstein, and I have a couple questions I wanted to GENERAL REPORTING SERVICE, INC. \ 2385 D-.W2' 56 1 ask you about It. 2 MR. PIERCE: While the witness is reviewing 3 this I'd just like to state that once again this is 4 a very difficult copy to read, many parts of which are 5 completely illegible and which the date itself is very 6 difficult to ascertain. 7 MR. DAVIS: You agree, Stanley, that the date 8 looks like August 25th, 1964? 9 MR. PIERCE: To the best -- or '69. If you 10 take a look at it, Gary, you'll see the same thing. 11 I don't think we need to debate about that. 12 A As best I can, yes, sir. 13 Q Okay. Exhibit 21 which you have just reviewed talks 14 about a meeting that was held to discuss the chloracne 15 problem, correct? 16 A That's correct. 17 Q And there is a chronological chart of process changes 18 attached to this which the memo itself mentions that 19 you presented at the meeting. 20 MR. PIERCE: May I see that? Object to the 21 form and to the characterization of the chart but -- is 22 there a question? 23 A I did not see a table or chart of process changes as 24 such. 25 Q What is the table that's on the third page or chart on GENERAL REPORTING SERVICE, INC. 2386 57 1 the third page? 2 A Well, as best I can read it the chart on the third page 3 is entitled "Materials Tested" and those are process 4 materials that have been tested. 5 Q Okay. If you don't mind me stepping around here. We 6 may have a page of this missing and it's one of the 7 things I am trying to determine. If you notice on 8 page 1 of Exhibit 21 it says: "L. Silverstein present 9 a chronological chart of the process changes, et 10 cetera, relating such changes to the chloracne problem." 11 Do you know if that is any earlier document that 12 we have looked at? 13 A I don't know to be honest with you. I didn't see a 14 chart that, you know, that fit that description. 15 Q Okay. 16 A In that document. 17 Q Okay. Then the remaining pages of the document deal 18 with process materials that were sampled and tested on 19 rabbit ears, is that -- and also there is some that 20 were tested on the bellies of rabbits, I believe. 21 MR. PIERCE: Objection. The document speaks 22 for itself. 23 A The first three tables appear to be process materials 24 that were tested on animals. The next one is wipe test * for 199 which are not process samples, of course, and GENERAL REPORTING SERVICE, INC. i 2387 58 1 then the last one I didn't look at again. 2 Q These are tests that were done on the -- either the 3 process materials or the wipe samples from the 4 trichlorophenol production building? 5 HR. PIERCE: Once again I renew my objection. 6 The document speaks for itself. 7 Q Is that correct? 8 A To the best of my knowledge, yes. 9 Q When the trichlorophenol production process at the 10 Midland plant was shut down temporarily in 1964, in '65 11 did Dow purchase 2,4,5-T from other suppliers? 12 MR. PIERCE: Objection to the form. There is 13 no foundation. Answer to the best of your ability. 14 A I wasn't involved in that. I don't remember to be 15 honest with you. 16 Q Do you know if Dow ever purchased trichlorophenol from 17 other suppliers? 18 A I believe they did. 19 Q Was it during the time that the Dow process was 20 temporarily shut down? 21 MR. PIERCE: Objection to the form. 22 A Probably. It's logical. 23 Q Let me show you what's been marked as Exhibit 11 and 24 first of all let me identify it. It's a letter or a 25 memo dated March 10th, 1965, from L. G. Silverstein to GENERAL REPORTING SERVICE, INC. 2388 59 1 a long list of what appear to be Dow employees on Dow 2 stationery. 3 First of all, what is the subject of this memo? 4 HR. PIERCE: You want him to read the title? 5 Q Please read the title because I didn't in Exhibit 11. 6 A You or me? 7 Q Either. 8 MR. PIERCE: I will read it. "Hazard of 9 Monsanto-T Acid" appears to be the title. 10 MS. JONES: I couldn't hear it. 11 MR. PIERCE: "Hazard of Monsanto-T Acid". And 12 LeeAnn, the date is March 10th of what appears to be 13 1965. 14 A Okay. 15 MR. PIERCE: All right. The second page, 16 LeeAnn, also has a legibility problem. 17 Q Can you attempt to read the second page for the record, 18 Mr. Silverstein? 19 MR. PIERCE: If you can. 2 0 A Just the sentence? 21 Q Yes. 22 A "I believe Dow has a definite obligation to advise 23 Riverdale and Woodbury of the problem immediately." 24 Q Okay. Can you tell the jury what problem that you were 25 referring to? GENERAL REPORTING SERVICE, INC. 2389 60 1 A Well, as stated in the memo, some material contaminated 2 with acnegen. 3 Q This was Monsanto trichlorophenol that was contaminated 4 with the acnegen? 5 MR. PIERCE: Objection to the form and 6 characterization. 7 Q Is that correct? 8 MR. PIERCE: Answer it to the best of your 9 ability. 10 A Yes, sir. 11 Q And what is Woodbury and Riverdale? 12 A At this time I honestly don't remember what they were. 13 Q Were either Woodbury or Riverdale Monsanto facilities, 14 do you recall? 15 A I do not know. 16 Q Does Dow have any facilities in Woodbury or Riverdale? 17 A Not to my knowledge. 18 Q Okay. Do you know if any action was taken as a result 19 of the memo which has been marked as Exhibit 11 that 20 you wrote? 21 A I honestly do not know. 22 Q Was there a new process implemented by Dow in around 23 1965 and early 1966 for the production of 24 trichlorophenol at the Midland plant? 25 A To the best of my recollection a new plant started GENERAL REPORTING SERVICE, INC. 2390 61 1 about 1967. 2 Q Okay. And just so that we can be clear on the date, 3 I'd like to refer you back to Exhibit 5 which I have 4 and I will give you as soon as I find the right page. 5 If you will look at page 13, the last paragraph. 6 A Yes, sir. 7 HR. PIERCE: Are you asking hist about his 8 current recollection or -- 9 Q I am asking if Exhibit 5 which is a memo that you wrote 10 or dictated refreshes your recollection as to the date 11 the new plant commenced? 12 A Not really. 13 Q You stated there it commenced in 1966? 14 A Yes, sir. 15 MR. PIERCE: I'm sorry. Were you asking him 16 does the document appear to say that when you say "you 17 stated there"? You are not dealing with his previous 18 statement of testimony but the document, is that 19 correct? 20 MR. DAVIS: Of course. 21 MR. PIERCE: All right. 22 Q You don't know of any facts today that contradict the 23 1966 commencement of operation date that you have 24 stated in Exhibit 5? 25 A No, sir. GENERAL REPORTING SERVICE, INC. 2391 V-3H^ 62 HR. PIERCE: I>d like to just place an objection in that the statement that you referred him 3 to even there in that document says as I remember it. 4 Q Okay. We have other documents as veil that ve can 5 refer to if that's a question. But what I want to 6 ask you is how Dow went about developing the new 7 process for production of trichlorophenol that was 8 commenced in approximately 1966? 9 MR. PIERCE: Objection to the form, it's 10 outside of this witness's knowledge. But answer it to 11 the best of your ability. 12 A It was a combination of'some Dow research and purchase 13 of some technical information from another company. 14 Q You went to Europe in 1964 to look at some other 15 chemical companies' processes for trichlorophenol, 16 didn't you? 17 A Yes, sir, I was one of a couple guys. 18 Q Who else went with you? 19 MS. JONES: Excuse me. Mr. Silverstein, could 20 I ask you to speak up a little bit? 21 A I'm sorry, LeeAnn, but my attorney won't let me get 22 close to this thing. 23 MS. JONES: Stan, are you keeping him from the 24 speaker? 25 MR. PIERCE: I am moving it over now, LeeAnn. GENERAL REPORTING SERVICE, INC. 2392 63 1 A My recollection is that Mr. A1 Lueck and a Mr. Walt 2 Trapp were the other members of the team. 3 Q And you visited aFrench chemical company? 4 A I believe so. 5 Q And a German chemicalcompany? 6 A Yes, sir. 7 Q And what was the name of the German chemical company? 8 A Boehringer. 9 Q The one we have been speaking of previously that also 10 sent the letter that has been marked as Exhibit 6, is 11 that correct? 12 A I believe so. 13 Q What did you ascertain on that trip about technology to 14 produce trichlorophenol from your perspective as an 15 industrial hygienist? 16 MR. PIERCE: Object to the form of the 17 question. You can answer. 18 A Well, my part in the mission was to assess the 19 company's knowledge of the health hazards involved and 20 so I did that at both places. 21 Q What did you learn about Boehringer's knowledge of the 22 health hazards of dioxin or TCBD? 23 MR. PIERCE: Objection to the form. 24 A They seemed to be quite knowledgeable. 25 Q And what specifically did they tell you at that point? GENERAL REPORTING SERVICE, INC. 2393 0-3.4 "7* 63 1 A My recollection is that Mr. A1 Lueck and a Mr. Walt 2 Trapp were the other members of the team. 3 Q And you visited aFrench chemical company? 4 A I believe so. 5 Q And a German chemicalcompany? 6 A Yes, sir. 7 Q And what was the name of the German chemical company? 8 A Boehringer. 9 Q The one we have been speaking of previously that also 10 sent the letter that has been marked as Exhibit 6, is 11 that correct? 12 A I believe so. 13 Q What did you ascertain on that trip about technology to 14 produce trichlorophenol from your perspective as an 15 industrial hygienist? 16 MR. PIERCE: Object to the form of the 17 question. You can answer. 18 A Well, my part in the mission was to assess the 19 company's knowledge of the health hazards involved and 20 so I did that at both places. 21 Q What did you learn about Boehringer's knowledge of the 22 health hazards of dioxin or TCBD? 23 MR. PIERCE: Objection to the form. 24 A They seemed to be quite knowledgeable. 25 Q And what specifically did they tell you at that point? % GENERAL REPORTING SERVICE, INC. 2394 64 A I don't remember. I'm sorry. Q Okay. It was ultimately Boehringer technology that Dow 3 utilized to design the new plant that commenced in 4 approximately 1966, is that right? 5 MR. PIERCE: Objection. But if you are 6 capable of answering it* ~ 7 A I believe so. 8 Q Was it true that when you visited Boehringer that the 9 Boehringer employees that you spoke with expressed that 10 they were interested in helping Dow or any other 11 chemical company to reduce exposure to the 12 chloracnegens? 13 MR. PIERCE: Objection to form. 14 A To the best of my recollection, yes. 15 Q And that Boehringer sold Dow the technology for a 16 nominal fee? 17 MR. PIERCE: Objection to the form and 18 characterization of fees. 19 A I don't remember having any part in the fees, sir. 20 Q Let's refer to Exhibit 5 which I think you still have 21 close to you. On page 11. 22 In Exhibit 5 on page 11 you refer to the 23 transaction as being one with a nominal fee, is that 24 right? MR. PIERCE: Are you asking him is that what GENERAL REPORTING SERVICE, INC. 2395 o a-fv- .J...... 1 2 3A 4Q 5A 6Q 7 8 9A 10 11 Q 12 A 13 Q 14 A 15 16 Q 17 18 A 19 Q 20 21 A 22 23 24 25 65 is on that document? MR. DAVIS: Yes. i That's what it says. And you wrote this document? I believe so. What happened to the old plant that had been shut down in 1965. MR. PIERCE: Objection to the form. At some time after shutdown it was dismantled and disposed of. How was it dismantled? Very carefully. With great precautions. And how was it disposed of? I don't really have first-hand knowledge of that to be honest with you. Do you know if the parts were buried? MR. PIERCE: Objection. Asked and answered. I don't know for sure. What do you recall? I mean you obviously recall something about that. Oh, yes, but the recollection is really, you know, not specific, vague. In general, that some of the equipment was cleaned up and salvaged and others sent to disposal. Dow had its own waste disposal firm -- not firm but group.in-house that made the decisions on GENERAL REPORTING SERVICE,-INC. 0- 66 1 best disposal methods. 2 Q And when you say that it was dismantled very carefully 3 with great precautions, what precautions were taken? j4 A My recollection is it was done by a contractor that was 5 given very thorough training in the risks and the 6 precautions that we felt they should take and then 7 monitored by Dow personnel to be sure they did that. 8 Q Were there specific precautions as to protective 9 equipment? 10 A 11 Q I honestly don't know that at this point. Do you recall anything about the new process that was I 12 commenced in approximately 1966? j j13 MR. PIERCE: Objection. Asked and answered. 14 Q As far as the reaction steps go? 15 MR. PIERCE: Continue the objection. 16 A I remember nothing of the technology of the process 17 itself, no. 18 Q Okay. You do recall that the levels of dioxin in the 19 new process were less th%ough, don't you? 20 MR. PIERCE: Objection to the form. 21 A Yes, sir. 22 Q Do you recall the method with which the reactants were 23 added to the reaction vessel to control the temperature and pressure of the reaction? A Not at all. GENERAL REPORTING SERVICE, INC. 2397 67 1 HR. PIERCE: Objection to the form of the 2 question and it's completely vague. I'm sorry, what 3 was your answer? 4 A I said not at all. 5 Q You mentioned earlier, I believe, that you were the 6 safety person for the trichlorophenol plant for a 7 period of about a year. What was your position after 8 that? 9 A A moment to try and remember, please. I believe that I 10 went to the chlorinated solvents industrial hygiene 11 project. 12 Q Did you still have some involvement with the 13 trichlorophenol plant or with the particular products 14 made at that plant after 1965? 15 A I had essentially no involvement after I had moved to 16 the other -- the new project. 17 Q Might you be a little vague about the dates when you 18 moved to the other project? I'm just trying to 19 establish what your involvement was. 20 A I'm pretty sure -- 21 MR. PIERCE: I'd like to make an objection. 22 The question was asked rnd answered. Go ahead. 23 A I am pretty sure that I moved into the solvents 24 project in 1967. 25 Q Okay. I just want to show you what's previously been GENERAL REPORTING SERVICE, INC. 2398 DW'fJi' 68 1 marked as first of all Exhibit 15 which is a memo from 2 L. G. Silverstein to A. F. Lueck, L-u-e-c-k, 3 Trichlorophenol Plant, August 16th, 1966, on Dow 4 Chemical stationary. 5 Is this a memo that you authored, Mr. Silverstein? 6 A It appears to be a copy of one I authored, yes. 7 Q Let me show you Exhibit 16 which is a memo L. G. 8 Silverstein to C. A. Highhill, 2,4-D Plant, Dow 9 Chemical, August 16th, 1966. Is this a copy that you 10 authored, Mr. Silverstein? % 11 A It appears to be a copy of a memo that I authored. 12 Q Let me also show you a memo that's been marked as 13 Exhibit 17 -- actually a letter that's been marked 14 as Exhibit 17 from L. G. Silverstein to Dr. Henry 15 Gilman, Department of Chemistry, Iowa State University 16 of Science and Technology, dated January 17th, 1967. 17 If you will take a look at this, please. 18 One of the things I wanted to ask you about 19 Exhibit 17 is what, if you know, type of testing was 20 Dr. Gilman doing in 1967 that this memo refers to or 21 letter refers to? 22 A To my recollection I rah into or, you know, found a 23 chemical abstract, you know, describing that he was 24 doing -- that he had made or was doing something with 25 tetrabromodioxin and wrote and requested the sample GENERAL REPORTING SERVICE, INC. 2399 69 1 that's described there. But I would -- you know, could 2 only say that he was an*academic in my recollection. I 3 have no idea what he was doing with the stuff. 4 Q Why did you tell him that clean-up and housekeeping 5 should be the same as required for work with 6 radioisotopes generally and better than is normally 7 required for Carbon-14 work? 8 A Because my background as a radiation safety specialist 9 I used that analogy once in a while to, you know, 10 people who were knowledgeable in radioactive work. 11 They could readily understand what I was talking about 12 in terms of the precautions needed. 13 Q Okay. In addition to the testing of the chloracne 14 producing materials on rabbit ears, Dow also caused 15 some tests to be done on human beings, correct? 16 MR. PIERCE: Objection to the form of the 17 question, to the characterization of what Dow did or 18 did not do. But answer the question. 19 A I recall some -- oh, you know, knowing that that had 20 happened, yes. 21 Q Do you recall any of the details of that? 22 A My recollection is that it was a consulting 23 dermatologist in the East who had done some human 24 volunteer studies. 25 Q These were prisoners that were the so-called GENERAL REPORTING SERVICE, INC. 2400 0-^1 70 volunteers, correct? MR. PIERCE: I really object to the 3 characterization, to the use of innuendo as completely 4 unnecessary. But go ahead and answer. 5 A I remember hearing that, yes. 6 Q Just let me rephrase the question. The persons upon 7 whom the materials were tested were prisoners, is that 8 correct? 9 A I have no first-hand knowledge of that. I heard it, 10 yes. 11 Q Let me refer you to Exhibit 5, an insert directly 12 after page 13 of Exhibit 5. In Exhibit 5 you discuss 13 the human testing that we have been referring to, 14 correct? 15 MR. PIERCE: If you ask him -- are you asking 16 him if that's what the document indicates? 17 MR. DAVIS: I am asking him if that's what he 18 wrote in Exhibit 5. 19 A It looks like something I wrote, yes, sir. 20 Q Concerning human testing of these materials on 21 prisoners? 22 A I see the human testing is the title. 23 MR. PIERCE: I don't -- Mr. Davis, I object. 24 I don't see the word prisoners on this page. Nor may a 25 prisoner not be a volunteer. / GENERAL REPORTING SERVICE, INC. 2401 71 1 Q You understood or at least you heard these were 2 prisoners that were tested, correct? 3 A By word of mouth is my recollection, yes, sir. 4 Q Were there other chlorophenol materials that were 5 produced in the Midland plant that caused the same type 6 of skin reaction on rabbit ears as the materials from 7 the trichlorophenol process? 8 MR. PIERCE: Objection to the form of the 9 question. 10 A Well, I learned in the course of my involvement that 11 there had been past experience with that, yes. 12 Q Were some of these other materials called Dowicides? 13 A Yes. 14 Q Let me show you Exhibit 13 and let me identify that as 15 a memo from L. G. Silverstein to J. B. Fernandez, 16 Organic Chemicals Product Research, Dow Chemical, April 17 10th, 1970. 18 MR. DAVIS: Still with us, LeeAnn? 19 MS. JOKES: Yes. 20 Q Are you the author of this memorandum, Mr. Silverstein? 21 A It appears to be something I wrote, yes, sir. 22 Q This memorandum mentions other toxic effects of known 23 or suspected acnegens must be kept in mind. What are 24 those other effects that you're aware of? 25 A The more familiar effects of injury to eyes and skin; GENERAL REPORTING SERVICE, INC. 2402 0 72 1 corrosive injury in particular is what I had in mind, I 2 think. 3 Q Are you aware of any other effects as we sit here today 4 that you associate with exposure to dioxin? 5 MR. PIERCE: Objection to the form. 6 A I missed your last word. % 7 Q Are you aware today of other health effects other than 8 chloracne that you associate with exposure to dioxin? 9 MR. PIERCE: Continue the objection. 10 MS. JONES: I object to the extent it's 11 calling for any sort of an expert opinion. 12 Q You may answer. 13 A Yes. Once again I'm not a toxicologist. I have been 14 following the veterans' concerns and the public press 15 which is not the best scientific journal and I have 16 reservations. 17 Q You were aware, weren't you, that in the rabbit tests 18 that Dow was doing that* Dow found liver effects as well 19 as the skin effects? 20 A Yes, sir. 21 MR. PIERCE: Objection to the form and as to 22 the broad generalization and nonspecific nature of the 23 question. 24 Q I'll be more specific if Mr. Pierce wants me to be. 25 That the Dow tests on the materials from the GENERAL REPORTING SERVICE, INC. i 2403 | i Q, 5 o o 73 1 trichlorophenol process that contained dioxin also In i 2 addition to affecting the skin of the rabbit's ears 3 would cause toxicity to the livers of the rabbits, Is 4 that correct? 5 MR. PIERCE: Continue the objection. 6 A I was aware of this. 7 MS. JONES: I couldn't -- 8 A I was aware of this, LeeAnn. 9 MS. JONES: Was? 10 A Yes. 11 MS. JONES: Thank you. 12 Q You were aware of that in the 1964-1965 time frame? 13 A Yes, sir. 14 Q Did you know about any subsequent process changes that 15 were made in the Dow process after 1966, the one that 16 we had discussed with the German process? 17 MR. PIERCE: Objection to the form. This 18 question has been asked and answered numerous times 19 during this deposition. But go ahead. 20 Q You may answer. 21 A No, sir. 22 Q Ever hear of a xylene extraction step that was put into 23 the trichlorophenol process to reduce the concentration 24 of dioxin even further? 25 MR. PIERCE: Objection to the form. % GENERAL REPORTING SERVICE, INC. 2404 0-5.501 74 1 A No, sir. 2 Q Okay. Have you ever seen the document that is marked 3 as Exhibit 19? 4 And you might read the title of it, Stanley, since 5 you got it there. 6 HR. PIERCE: It has a cover page saying "NaTCP 7 Solution IWD". 8 A I guess I have to read every word to determine -- 9 Q Go ahead. 10 A I don't believe I have ever seen this document, sir. 11 Q Okay. Thank you. With the process that Dow 12 implemented in around 1966 was there a danger of 13 over-pressurization of the trichlorophenol reactor? 14 MR. PIERCE: Objection. Once again, the 15 witness has answered numerous times that he is not 16 familiar with the process. But go ahead once again. 17 A I am not qualified, I don't know anything about that. 18 Q Do you recall at all whether the process, particularly 19 the trichlorophenol reactor, had a ruptured disk? 20 A I don't know. 21 Q Have you ever had any communications with any 22 individual from Hercules, Incorporated, or what was 23 formerly known as the Hercules Powder Company? 24 HR. PIERCE: At any time? 25 MR. DAVIS: At any time. GENERAL REPORTING SERVICE, INC. 2405 V-9St>3- 75 1 A The only one I recall is Emil Christofano who is a 2 friend of mine. 3 Q What communications have you had with Mr. Christofano 4 concerning trichlorophenol or phenyoxy herbicides or 5 dioxin? 6 MR. PIERCE: Objection to the form of the 7 question. 8 MS. JONES: I object in that it's vague. 9 A I have never discussed these matters with him to my 10 recollection. 11 Q Have you ever had any communications with anyone 12 representing or working for Transvaal, Incorporated or 13 the Vertac Chemical Company? 14 A No, sir. 15 Q Is it fair to say that you determined that extreme 16 precautions were necessary to protect the workers in 17 the Dow trichlorophenol plant from exposure to dioxin? 18 MR. PIERCE: Objection to the form of the 19 question and specifically to the term he determined. 20 MS. JONES: I object also. 21 A In the context of the times, and remembering that 22 we didn't know a lot about what was going on, it was -- 23 it appeared to us that we should take extensive 24 precautions to protect our employees to minimize 25 exposure which is a basic precept of industrial GENERAL REPORTING SERVICE, INC. 2406 0 3.503 76 1 hygiene. 2 Q And you also determined, did you not, that the process 3 area for the production'of trichlorophenol needed to be 4 monitored with the wipe tests on a frequent basis 5 to determine the levels of contamination of dioxin in 6 the process area? 7 HR. PIERCE: Objection to the form of the 8 question. Also object to the statement that he 9 determined. But go ahead. 10 Q You may answer. 11 A We used wipe tests as a housekeeping indicator for the 12 production plant and kept it as clean as we were able 13 to achieve as evidenced by the wipe test data. 14 Q And there was also a chloracne hazard in the 2,4,5-T 15 production process, was there not, at least in 1964 or 16 '65 time frame? 17 MR. PIERCE: Objection to the form of the 18 question. 19 A Not to my knowledge based on what I recall of our 20 information. j 21 Q Did you test the 2,4,5-T processing area for the 22 presence of thematerials thatcausedchloracne? j 23 A I believe I did, yes. 24 MR. DAVIS: That's all Ihave. j ii 25 MR. PIERCE: Okay. When do you want to start GENERAL REPORTING SERVICE, INC. 2407 i| i 77 1 again? 2 MS. JONES: Was that all that Gary had? 3 (Conference off the record.) 4 MS. JONES: I have just a couple of documents. 5 Could I fax those documents to you guys somewhere? 6 MR. DAVIS: I don't know how we can do that, 7 LeeAnn. I don't know if this hotel has a fax. I mean 8 it's something you really need to be here for. 9 MS. JONES: I have got a document dated March 10 29, 1965. It is a memo prepared by Mr. Silverstein to 11 V. K. Rowe with a carbon copy of a whole list of 12 people, it's entitled "Report on the Chloracne Problem 13 Meeting on 3-24-65". 14 MR. DAVIS: Okay. I think we have introduced 15 that one. Let me -- it was difficult to read. No, 16 this is not it. I don't know that I have that. What 17 else? j 18 MS. JONES: Okay. I have got an April 25th, 19 1967 memo to K. E. Coulter, C-o-u-l-t-e-r, regarding 20 chloracne research program. i 21 MR. DAVIS: Going back to that first one, i 22 LeeAnn, was that with regard to the meeting in Midland? \ j 23 MS. JONES:Yes. 3-24-65 meeting. j ii MR. DAVIS: Okay. I may have that. I didn't I | realize it was from Mr. Silverstein. j1 j \ GENERALREPORTING SERVICE, INC. | ii 78 1 MS. JONES: It is part of the documents you 2 guys produced at Dr. Ratalik's deposition. 3 MR. PIERCE: Who is the author of the '67 4 memo? 5 MS. JONES: I can't tell from my copy. 6 MR. DAVIS: If you want to fax it up here ~ 7 MR. PIERCE: Is Mr. Silverstein even mentioned 8 on the 1967 one or is he the author? 9 MS. JONES: I can't tell from the copy that I 10 have got. That's what I wanted to ask him. 11 MR. DAVIS: I don't have that one. 12 (DepX# 22 marked.) 13 MR. DAVIS: What would you like to ask about 14 it? We have got the March 29th, 1965 document marked 15 as Exhibit 22 and we have the April 10th, 1970 document 16 marked already as Exhibit 13. 17 MS. JONES: Okay. Great. 18 EXAMINATION 19 BY MS. JONES: 20 Q Mr. Silverstein, would you like to take a couple of 21 minutes to look over those documents or do you feel 22 like you have already looked over them. 23 MR. PIERCE: Well, obviously he has not looked 24 over one of them. 25 Q Right, that's the March 29th. And to narrow it down to GENERAL REPORTING SERVICE, INC. 2409 79 1 save you some time the only things I am going to ask 2 you about are on the first couple of pages of that 3 document. 4 I just wanted to let you know for your purposes I 5 sun going to be asking questions about the first couple 6 of pages but you may want to look over the whole 7 document just to familiarize yourself with it. 8 A Yes, I think so. Okay. 9 Q Okay. You ready? 10 A Yes, ma'am. 11 Q Hr. Silverstein, the exhibit that has been marked as 12 Exhibit 22 which is a letter dated -- or a memo dated 13 March 29th, 1965, it appears to be authored by 14 yourself, is that correct? 15 A It appears to be a document I wrote, yes, ma'am. 16 Q And you signed it there at the bottom of page 5, is 17 this correct? 18 A Wait a minute. It looks like my signature, yes. 19 Q And what is that document entitled? 20 A "Report on the Chloracne Problem Meeting on 3-24-65". 21 Q And what was the purpose of your preparing that 22 document? % 23 MR. PIERCE: If you recall? 24 A I believe I was asked to write a summary of the 25 meeting, LeeAnn. GENERAL REPORTING SERVICE, INC. 2410 0 -9.501 80 1 Q I'd like to direct your attention to page 2 of that 2 document to help refresh your recollection. 3 MR. PIERCE: There is no indication the 4 witness needs his recollection refreshed. 5 MS. JONES: I'm not suggesting that he does. 6 Q Do you recall a Dr. Holder giving a report at that 7 meeting? 8 A In general terms, yes, I remember him reporting. 9 Q Do you recall what was the topic of Dr. Holder's 10 report? 11 A He reported on the medical findings and treatment of 12 the Dow employees. 13 Q Do you recall what if anything he reported about any 14 clinical studies that had been done on the workers from 15 Dow who had chloracne? 16 A I don't recall any details, I'm sorry. 17 Q Do you recall if chemical studies had been done on 18 those workers? 19 A I'm out of my field. What do you mean by clinical 20 studies, ma'am? 21 Q Mr. Silverstein, if I could refer you to page 2, about % 22 6 or 7 lines down, it states, and if you could just 23 confirm whether you recall this topic being addressed, 24 that he did review the clinical studies that are being 25 made on these people with emphasis on the liver function GENERAL REPORTING SERVICE, INC. 2411 81 1 tests? 2 A Yes, ma'am. I believe I was referring to blood 3 sampling. 4 Q Okay. And do you recall the next sentence, is this 5 correct that the memo states he mentioned the single 6 liver biopsy that has been taken and studied in which 7 the liver was normal although the man had a rather 8 pronounced case of chloracne, is that what you prepared 9 in that memo? 10 MR. DAVIS: Let me object to the reading of 11 portions of the document. You may answer. 12 Q Mr. Silverstein, you can go ahead and answer the 13 question. Did you report that in that March 29th memo? 14 A Yes, ma'am, to the best of my recollection that's what 15 I wrote. 16 Q Did you recall those liver biopsies having been done or 17 that particular liver biopsy? 18 A I remember a single liver biopsy being available to us 19 at that time, yes. 20 Q Do you remember what the result of that biopsy was? 21 A I remember being told that there was no liver injury 22 evidence. 23 Q And did the person on whom the liver biopsy was 24 performed have a case of chloracne? A According to Dr. Holder, yes. I never knew or met the GENERAL REPORTING SERVICE, INC. 2412 82 1 patient. % 2 Q Do you recall whether in the clinical studies that Dr. 3 Holder performed he found any other significant effects 4 other than chloracne among the Dow workers? 5 HR. DAVIS: I am going to object to the form 6 of the question as being vague. 7 MR. PIERCE: You can answer. 8 A Not to my knowledge. 9 Q Did you report in that March 29th, 1965 memo that Dr. 10 Holder reported to the group that he mentioned the 11 incidence of fatigue among the afflicted people as 12 being the only other significant finding in these 13 folks? 14 MR. DAVIS: Object. The document speaks for 15 itself. 16 Q Could you go ahead and answer, do you recall whether 17 you reported that he mentioned that at the meeting? 18 A I remember that being known in terms of the medical 19 department telling us about it that this seemed to be a 20 finding amongst the folks but I don't class that as a 21 clinical study. But I am a layman. 22 Q Do you also recall that there were no other significant 23 findings reported by Dr. Holder? 24 MR. DAVIS: Obj ection. 25 A That's my general recollection, yes, ma'am. GENERAL REPORTING SERVICE, INC. 2413 O'Z'Zlb 83 1 Q Do you recall back in 1965 what the limit of 2 detectability of TCBD using the gas chromatography 3 method was? 4 A My recollection is that, it was -- that it changed, of 5 course; with improvements that it was something like 1 6 ppm. That's the number I remember. 7 Q All right. Now, if you would take a look at the 8 exhibit that is dated April 10th, 1970, which I believe 9 already has been marked as Exhibit #13. 10 A Yes, ma'am. 11 Q Could you tell me who the author of that memo was? 12 A It appears to be a document that I authored. 13 Q Who did you send it to? 14 A J. B. Fernandez. 15 MR. PIERCE: Are you asking his independent 16 recollection now or what the document indicates? 17 MS. JONES: What the document indicates. 18 A It is addressed to J. B. Fernandez. 19 Q What was the topic of that memorandum? 20 A It is entitled "Dowicides Chloracne History". 21 Q Did you know in about 1970 at the time you prepared 22 that memorandum on April 10th, 1970, that studies which 23 had been done at that point indicated that the rabbit 24 ear test was more sensitive than human response to the 25 acnegen? *- % GENERAL REPORTING SERVICE, INC. 2414 0'5U 84 1 A I believe that's what I knew at the time or thought I 2 knew. 3 Q In reference to the 1967 study that Mr. Davis asked you 4 about earlier of the human volunteers, do you recall 5 that that study indicated that rabbits were at least 10 6 to 100 times more sensitive to 2,3,7,8-TCBD than the % 7 human volunteers who were exposed in the same manner? 8 MR. DAVIS: Objection to the leading question. 9 A I recall that I made that judgment, yes. 10 Q Since Mr. Davis has objected to the question I would 11 like to rephrase it. Do you recall anything, any 12 judgments that you made about the 1967 human volunteer 13 study of exposure to 2,3,7,8-TCBD as compared to the 14 rabbit ear studies? 15 A My recollection is that I judged that rabbit ears were 16 10 times more sensitive as an indicator than human 17 beings. 18 Q Mr. Silverstein, referring to many of the questions 19 that Mr. Davis has asked you today about precautions 20 that you either recommended or that were implemented by 21 Dow, what was the purpose of instituting those 22 precautions and procedures? 23 MR. PIERCE: Objection to the form of the 24 question. 25 Q You can go ahead and answer. -GENERAL REPORTING SERVICE, INC. 2415 >.3.913- 85 1 A The changes, the precautions were all aimed at reducing 1 2 exposure of Dow employees to the materials. 3 Q Were those all instituted after the 1964 incident of 4 Dow workers coming down with chloracne? 5 A Some of them were in force before that to my -- to the 6 best of my recollection, LeeAnn. 7 Q If you will bear with me for just a minute while I go 8 back through my notes. Hr. Silverstein, back in 1964 9 and 1965 did you know anything about the Hercules 10 process for manufacturing 2,4,5-T? 11 A No, ma'am. 12 Q Do you currently know anything about the Hercules 13 process for manufacturing 2,4,5-T? 14 A No, ma'am. 15 Q Do you have any way of knowing whether any differences 16 existed between the Hercules process and the Dow 17 process for manufacturing 2,4,5-T? 18 A In the course of my involvement in that Dow tested some 19 Hercules' products, that's the only knowledge I have. 20 Q But you have no knowledge about whether there were any 21 differences between the two processes used by the 22 companies? 23 A I have no knowledge on that subject. 24 Q Would you have any way of knowing whether differences 25 in the process used by Hercules as opposed to the GENERAL REPORTING SERVICE, INC. 2416 0-3-513 process used by Dow night have some effect on the sensitivity of the gas chromatography method for detecting TCBO in either the product or the waste of Hercules? MR. PIERCE: Objection to the form of the question and objection to this witness being asked areas far outside his expertise. MR. DAVIS: I join in that objection. You can go ahead and answer if you know. Well, they stole my answer. You are way outside of my area of expertise. I have no idea. That's a perfectly fine answer. Mr. Silverstein, based on your experience as an industrial hygienist would it be fair to say that different precautions are necessary in a laboratory setting than in an actual production setting? That's a fair generalization, yes, ma'am. So precautions and procedures that may be necessary in one setting may not be necessary or appropriate in another? MR. DAVIS: Objection to the leading question. Another good generalization. Mr. Davis referred to a French company that you visited when you went to Europe to investigate some other plant processes. Do you recall the name of that company? GENERAL REPORTING SERVICE, INC. 2417 0-3-514 87 1 A I do not, ma'am. 2 Q Mr. Silverstein, when did you first learn that Monsanto 3 had experienced problems with chloracne among its 4 workers at their plant in Nitro, West Virginia? 5 MR. PIERCE: Objection to the form and no 6 foundation. 7 Q First, to change that, did you ever learn that Monsanto 8 experienced any problems with chloracne among its 9 workers in Nitro, West Virginia? 10 A I remember becoming aware of that at sometime but I 11 don't remember when. 12 Q Do you remember ever learning that BASF experienced 13 problems with chloracne among its workers? 14 A I don't remember that, no, ma'am. 15 Q Do you ever remember that Boehringer, the German plant 16 that you visited, experienced chloracne with its 17 workers? 18 A Yes, ma'am, I do remember that. 19 Q Do you know when you first learned that? 20 A I don't know. 21 Q Do you have a recollection as to approximately when you 22 first learned that? 23 A Early in 1964 I think. 24 Q Did you ever learn whether Diamond Alkali ever 25 experienced any problems with chloracne among its GENERAL REPORTING SERVICE, INC. 2418 88 1 workers? 2 A I'm thinking. I don't remember knowledge on Diamond 3 Alkali, no. 4 Q Do you recall ever learning that Shone Polunc had a 5 problem with chloracne among its workers? 6 A No, ma'am. I didn't hear that name until I left Dow. 7 Q Have you learned since leaving Dow that Shone Polunc 8 had a problem with chloracne among its workers? 9 A No. You were the first to advise me. 10 MS. PIESCE: I wouldn't call that advising. 11 Q Do you recall ever learning whether Phillips Dufar had 12 a problem with chloracne among its workers? 13 A That name strikes a familiar bell in my recollection 14 but only the name, I don't remember details. 15 Q In investigating the problem that Dow experienced with 16 chloracne among its workers and in your job as an 17 industrial hygienist trying to come up with possible 18 solutions to that problem, would you have been 19 interested in investigating any plant that was 20 operating and its procedures which had managed not to 21 have any problem with chloracne in its production 22 process? 23 MS. PIESCE: Objection to the form of the 24 question. 25 MS. DAVIS: I join. GENERAL REPORTING SERVICE, INC. 2419 89 1 Q I will rephrase It. Mr. Silverstein, did you conduct 2 an investigation to determine possible process 3 improvements that you could make to solve the 4 difficulty that Dow was having with chloracne among its 5 workers? 6 MR. PIERCE: Objection to the characterization .7 and I think he's answered in respect to his knowledge 8 of production techniques earlier but go ahead and 9 answer. 10 A Well, I was I'm sure interested in ways to reduce the 11 problem and control it. That would include process 12 steps but I'd ask an engineer to go look for me in that 13 instance. 14 Q Would you have been interested in investigating the % 15 processes used by any company that did not experience a 16 chloracne problem? 17 MR. DAVIS: Objection, lack of foundation. 18 MR. PIERCE: Objection as to form. 19 A I would have been very interested in their industrial 20 hygiene procedures, definitely. 21 Q Were you aware in the 1960's that Hercules did not have 22 any problem with chloracne at its plants? 23 MR. DAVIS: Objection. Leading and lacks 24 foundation. 25 A I don't remember. % GENERAL REPORTING SERVICE, INC. 2420 90 1 Q Strike it. Were you aware whether or not Hercules had 2 a chloracne problem at its plant? 3 A I don't remember having a knowledge either way on that 4 one, LeeAnn. 5 Q If you had been aware at the time that Hercules did not 6 have chloracne among its workers would that have been 7 something that you would have been interested in 8 investigating? 9 MR. PIERCE: Objection. Completely 10 speculative. 11 MR. DAVIS: I join. 12 A I believe so. 13 MS. JONES: That's all I have. 14 MR. PIERCE: Thank you. We'll see you later. 15 MR. DAVIS: One follow-up. 16 EXAMINATION 17 BY MR. DAVIS: 18 Q Just going back to Exhibit 22 which was introduced by 19 Ms. Jones, this Exhibit 22 describes a chloracne 20 problem meeting on March 24th, 1965. Were you present 21 at that meeting, Mr. Silverstein? 22 A Yes, sir. 23 Q Was Mr. C. L. Dunn from Hercules present at that 24 meeting? 25 A I do not remember specifically, sir. GENERAL REPORTING SERVICE, INC. 2421 0 35ltf 91 1 Q I will show you Exhibit 22. Does that refresh your 2 recollection? 3 HR. PIERCE: Are you asking him if that's what 4 it says or whether it refreshes his recollection of C. 5 L. Dunn being present? 6 Q Does Exhibit 22 say that C. L. Dunn was present at the 7 meeting? 8 A Yes. 9 Q And you wrote Exhibit 22 shortly after that meeting, % 10 correct? 11 A Yes, sir. 12 Q And does Exhibit 22 also show that Dr. John Frawley 13 from Hercules was present at that meeting? 14 A The document showsthat, yes, sir. 15 MR. DAVIS: That's all I have. 16 MR. PIERCE: Okay. LeeAnn? 17 MS. JONES: Okay. 18 (Deposition concluded.) 19 -oOo20 21 22 23 24 25 GF.NERAL REPORTING SERVICE, INC. 2422 p. tS'Fs 92 1 STATE OF MICHIGAN > ) 2 COUNTY OF SAGINAW ) SS 3 4 I certify that this transcript, consisting of 92 5 pages, is a complete, true, and correct record of the 6 testimony of LAWRENCE fl. SILVBRETEIN held in this case 7 on July 18, 1990. 8 I also certify that prior to taking this deposition 9 LAWRENCE G. SILVERSTEIN was duly sworn to tell the 10 truth. 11 I also certify that I am not a relative or employee 12 of or an attorney for a party? or a relative or employee 13 of an attorney for a party? or financially interested in 14 the action. 15 16 July 24, 1990 17 J. Richard Loberg, RPR, C9R-2315 18 Notary Public, Saginaw County, MI 19 My commission Expires: 9-3-91 20 silver\jrl 21 22 23 24 25 GENERAL REPORTING SERVICE, INC. 2423 NEWMAN v. AT&T - Attachment to Memo of 11/29/91 - Exhibit of Documents (M ATTACHMENT TO MEMORANDUM OF NOVEMBER 29, 1991 (NEWMAN V. AT&T) EXHIBIT LIST 1. 2/22/71: Courtney, K. Diane et al,"Teratology Studies with 2,4,5-Trichlorophenoxyacetic Acid and 2,3,7,8-Tetrachlorodibenzop-dioxin", Toxicology and Applied Pharmacology.Vo1 20, pp. 396403, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina. This study was done with mice and showed that these compounds produced cleft palates and kidney malformations. (These samples were supplied by Dow Chemical with TCDD contamination of 0.5 ppm). Note: Based on other similar studies I have reviewed, the strain of mice used produces different results with different laboratories doing these tests. Pick the right mouse, and your product will appear to be harmless! In this particular test, even small amounts of TCDD caused adverse damage to the mice on an acute basis. What you would like to see are long term chronic effects from these same chemical samples. Current experts say that it will produce various forms of cancer in some of the test animals every time if you do a chronic test versus an acute test. 2. 6/4/73: Yoder, J. et al, "Lymphocyte Chromosome Analysis of Agricultural Workers During Extensive Occupational Exposure to Pesticides", Mutation Research. Vol 21, pp. 335-340. This study looked at exposed individuals just after a heavy spraying period and noted a marked increase in the frequency of chromatid lesions. This was done in Idaho and sponsored by the EPA to evaluate the effects of pesticide exposure on human health. 2.4-D was the particular herbicide that most of the workers were exposed to, but some were also exposed to 2,4,5-T. Note: Once again, this was only an acute study, but it showed immediate effects in many workers. If a chronic testing were done over a period of years, the true results would be known. 3. 6/21/73: Russian Study by Pilinskaya, M.A., "Cytogenetic Effect of the Herbicide 2,4-D on Human and Animal Chromosomes", Tsitologiva i Genetika. Vol. 8, No. 3, pp. 202-206 (1974). The study looked at the cytogenetic action of 2,4-D in lymphocyte cultures of human peripheral blood and in bone-marrow cells from unpedigreed white mice. It was shown that human chromosomes in cultures were more sensitive to the injurious action of 2,4-D than that of the mice. The results obtained enabled the Russians to assign the herbicide 2,4-D to the class of substances presenting a potential genetic hazard to humans. 2425 h-P:C 4. 11/3/81: Burmeister, Leon F., et al, "Leukemia and Farm Practices in Iowa", American Journal of Epidemiology", vol. 115, No. 5, pp. 720-728. Death certificate analyses of 1675 white, male Iowans over age 30 years who died of Leukemia in 1964-1978 were completed. The highest ratios of deaths were in those counties with the largest number of acres treated with herbicides among persons 65 years of age or younger. The types of leukemia causing elevated mortality in Iowa farmers were CHRONIC LYMPHATIC LEUKEMIA and unspecified lymphatic. 39.5% of the deaths from leukemia in white males over 30 years of age were farmers in the 1964-1978 period studied. (It noted a similar Nebraska study where 39.9% of the leukemia deaths in white males over 30 years of age were also farmers). The study noted that one mechanism of increasing the risks for farmers for leukemia and other cancers is contamination of shallow farm wells and farm ponds. 5. 10/10/85: Rivarola, V.A., et al, "DNA and Protein Synthesis I n h i b i t i o n in C h i n e s e H a m s t e r Ovary Cells by Dichlorophenoxyacetic Acid", Toxicology Letters, Vol. 29, pp. 137-144. This was a study done in Argentina that tested the health effects of 2,4-D on DNA and protein synthesis and determined that 2,4-D affects both of these. The way these cells were affected depended on their stage of growth and the method of treatment. The effect was expressed as an inhibition of DNA and protein synthesis. 6. 10-18 March 1987: From the World Health Organization: International Agency for Research on Cancer meeting in Lyon, France on "IARC Monographs on the Evaluation of Carcinogenic Risks to Humans", pp. 156-160 of Supplement 7 on "CHLOROPHENOXY HERBICIDES". The overall view of the expert opinions given was that these herbicides were possibly carcinogenic to humans. THE CONSENSUS OF OPINION WAS BASED ON THE FACT THAT ENOUGH TESTING HAD NOT BEEN DONE ON ANIMALS. Comment: The arguments presented here centered on acute exposures. If it doesn't give you cancer immediately, then it gets a "possible category" rating. This category is generally used for agents for which there is limited evidence in humans in the absence of sufficient evidence in experimental animals. 7. 10/7-8/88: First Annual Scientific Assembly on Environmental Health in New Orleans. They presented talks on: ROUTES OF EXPOSURE, THE POLITICS OF CANCER; HOW CHEMICALS AFFECT HEALTH; REPRODUCTIVE TOXICITY; FEDERAL/STATE INVOLVEMENT; HEALTH STUDIES; NEUROTOXICITY; CASE STUDIES; and several others. Video tapes are available on all these talks for $14.95 each or a set of all seven for $65.00. Comment: These tapes were highly recommended by Mike Caddell. (Dr. Marvin Legator appears on two of the tapes). 8. 1/88: USDA Publication from the Pacific Northwest Region of 2426 -- z.- O <5.^3 The U.S. Forest Service on "Managing Competing and Unwanted Vegetation: Final Environmental Impact Statement", Section 6 titled "Data for evaluation of Human Epidemiology." This study evaluates exposures of2,4-D and/or 2,4,5-T and looks at the types of cancers associated or possibly associated with them including lung cancer, stomach cancer, leukemia, Hodgkin's disease, Non-Hodgkin's Lymphoma, and soft tissue sarcomas. It also implicates reproductive effects and clearly states there are neurologic effects. 9. 1988: Stokes, C. S., et al, "Agricultural Chemical Use and Cancer Mortality in Selected Rural Counties in the USA", Journal of Rural Studies. Vol. 4, No. 3, pp. 239-247. Findings of this study suggest that agricultural chemical use is related to county cancer mortality. For three of the five categories of cancer included, agricultural chemical use was the best predictor of cancer mortality. They look at groupings of cancer in : Genital, urinary, lymphatic and hematopoietic, respiratory, and digestive areas of the body. In four of these five areas, herbicide use in particular was significantly related to cancer rates. The respiratory cancer category was the only one that did not rate high from these herbicide exposures. 10. 1980's (? ) : "Genetic Toxicology: An Agricultural Perspective", edited by Fleck, R.A. et al . This study states "As competing organisms evolve resistance to commonly used agents, new and more effective poisons and repellents must constantly be developed. The fundamental problem in pesticide development is to produce chemicals that act specifically against certain organisms without adversely affecting others. BECAUSE OF THE SIMILARITIES IN THE STRUCTURAL, METABOLIC AND GENETIC COMPONENTS OF ALL LIFE FORMS. ABSOLUTE SPECIES SPECIFICITY IS FREQUENTLY DIFFICULT TO OBTAIN. Furthermore, such toxic chemicals improperly used may engender biological effects bevond those for which they were originally manufactured." Note: This study shows the specific genetic centers that 2,4-D and 2,4,5-T attack. 11. 4/4/90: Editorial by Blair, A., "Herbicides and Non-Hodgkin's Lymphoma: New Evidence From a Study of Saskatchewan Farmers", Journal of the National Cancer Institute. Vol. 82, No. 7, pp. 544-545. Evidence from 69,513 Saskatchewan farmers, age 35 and older, which provide further evidence that the use of herbicides is associated with the risk of non-Hodgkin's lymphoma. Mortality from non-Hodgkin's lymphoma rose significantly with increasing numbers of acres sprayed with herbicides, particularly on smaller farms where the farmer is more likely to have personally engaged in herbicide application. He points out that "The International Agency for Research on Cancer concluded that the evidence for carcinogenicity of 2,4-D and 2,4,5-T in animals was inadequate. This presents a dilemma to the scientific community in how to draw conclusions regarding carcinogenicity of a substance when the epidemiologic and experimental data do not agree, especially 2427 _ ^2 _ Q -3 6c9>4 in situations where the epidemiologic evidence is positive and experimental evidence is not." He further states "EXPERIMENTAL INVESTIGATIONS OF PESTICIDES SHOULD UTILIZE DERMAL EXPOSURE, THE PRINCIPAL ROUTE OF OCCUPATIONAL EXPOSURE IN HUMANS." 12. 3/90: "Environmental Health Monthly"."Abstract",Vol.2, No 6. This is an abstract from the study presented in my exhibit #9 above. It makes a further point in this review by saying "cancer mortality rates tend to underestimate the disease experience of a population because the actual numbers of people with the disease at any given time is greater than the number of people who have died from it. Comment: What this is saying is that the numbers of people who have contracted cancer and are still living, exceeds those who have previously died from it. You could conclude that something has been introduced into the environment in the last 30 to 40 years (the time for many chronic forms of cancer to show themselves) that has changed the rate at which the population is getting cancer. We you see how these herbicides have affected our water supplies, our farm crops and farm animals, gotten into almost all of our food chains, our fish, and then when banned from this country, the chemical manufacturers take it to third world countries and spray it on their crops which are exported back to us, it is no great mystery why so many more people are now getting cancer. The irony of all this is that companies like Dow are still telling everyone that their herbicides are perfectly safe. 13. 4/4/90: Wigle, D.T. et al, "Mortality Study of Canadian Male Farm Operators: Non- Hodgkin's Lymphoma Mortality and Agricultural Practices in Saskatchewan", Journal of the National Cancer Institute. Vol. 82, N o .7, pp. 575-582. This is the full study of the editorial mentioned above in my exhibit #11. They conclude by showing that these farmers who have been exposed to herbicides have a 220% greater risk in dying from non-Hodgkin's lymphoma that those in other occupations. 14. November 1990: 33 Law Reoorter.p. 373. "Nonmedical Expert Witness With Adequate Training, Education, and Experience Could Express Novel Cancer-Causation Theories." Rubanick v. Witco Chem. Corp.,576 A.2d 4 (N.J. Super. Ct. App. Div.1990^. The appeals court held that a biochemists who had done extensive research in cancer causation was qualified to testify on cancer development and related scientific matters based on his knowledge, training, and experience. Even though his theory was a novel scientific opinion that had not been accepted by at least a substantial minority of the scientific community, the court held that lack of agreement within the scientific community goes to the weight of the testimony - not its admissibility. Another article was: "Expert's Testimony Was Admissible Despite the Lack of Epidemiological Evidence Linking Chemical Exposure to Colon Cancer." Christophersen v. Allied-Sianal Corp., 902 F.2d 362 (5th Cir. 1990). The court said that, generally, 2428 * y- of detail. Even the damages are broken down into numerous sub categories . This has to be a strong way of intimidating your opponent when you have a good case. If this were read to a jury before the presen" .tion of your evidence, it would be very hard for the jury not o be greatly affected. Exhibits were attached to this petition giving credible evidence to each and every point claimed. NOTE: Mike Caddell recommended that if your case should go before mediation, or you have a serious settlement conference with Dow, that you insist on having in-house management present, besides their lawyers. The attorney's usually do not have the authority to offer beyond a certain amount, and Mike said it has been his experience that they will often "low ball" the final offer just to get a complete look at your whole case. If their insurance carrier is involved, insist on having a management representative there that has the authority to make a final offer. 20. 8/2/91: Legator Exhibit #1 from his deposition titled "Possible Manifestations of Mutational Events in Humans." This was his way of showing a jury exactly how the herbicides are absorbed into your body through the skin and attack the DNA, which goes on to the various cell groups and picks the course of attack for your body. He has a lot of credibility in his field of medicine and has appeared all over the world talking about this process. IMAN V . AT&T - #1 - #20 O co cArr T* C\i d> o 9 1 - 0 '***' ___ EiZ I 0 ~ - I -^4 ' X ^ '/A nvu/ro3M TOXICOLOGY AND APPLIED PHARMAC'OLCXIY 2 0 . 3 9 6 - 4 0 3 ( 1 9 7 1 ) Teratology Studies with 2,4,5-Trichlorophenoxyacetic Acid and 2,3,7,8-Tetrachlorodibenzo-P-dioxin K. D iane Courtney* and John A. Moore National Institute o f Environmental Health Sciences, P.O. Box 12233, Research Triangle Park. North Carolina 22709 Received February 22, 1971 Teratology Studies with 2,4,5-Trichlorophenoxyacetic Acid and 2,3,7,8Tetrachlorodibenzo-F-dioxin: Courtney, K. D., and M oore, J. A. (1971). Toxicol. Appi Pharmacol. 20, 396-403. The herbicide 2,4,5-trichlorophenoxyacetic acid (2.4,5-T). and 2,3.7,8-tetrachlorodibenzo-pdioxin (TCDD) were teratogenic in the CD-I, DBA/2J, and C57B1/6J strains of mice. Both compounds produced cleft palates and kidney malformations. When these compounds were administered in combination, the activity was not potentiated at the doses employed. In the CD rat, 2,4.5-T was neither teratogenic nor fetotoxic. However, TCDD produced kidney anomalies. Prenatal administration of 2,4,5-T did not affect the postnatal growth and development of the CD rat. The herbicide 2.4,5-trichlorophenoxvacetic acid (2,4,5-T) is one of the chlorinated phenoxyacid class with extensive utilization as a defoliant (Audus, 1964). Pharmaco logic and toxicologic reports considered this compound to be only moderately toxic in animals (Drill and Hiratzka, 1953: Rowe and Hymas, 1954). A recent report found 2,4,5-T to be teratogenic in mice and rats (Courtney et al., 1970), but it was later found that the sample of 2.4.5-T used contained 30 ppm of 2,3,7,8-tetrachlorodibenzop-dioxin (TCDD). a by-product formed during the commercial manufacturing process. TCDD and other closely related compounds are considered extremely toxic and have been implicated in outbreaks of chloracne in chemical workers (Schulz, 1968). lethal hepatonecrosis in rabbits (Schulz, 1968). chick edema factor (Higginbotham et al.. 1968), and a disease in animals fed toxic fat (Allen and Carstens, 1967). Since it was not known whether the teratogenic results previously reported were due to 2,4,5-T. TCDD or the combination, a study was initiated in mice and rats to determine the teratogenic aewent. MATERIALS AND METHODS Two different samples of 2.4.5-T and one sample of TCDD were used. All samples were supplied by Dow Chemical Company, Midland, Michigan. The samples o! 2.4.5-T designated by the authors as technical (2,4,5-T/tech) and analytical (2.4,5-T anal) grade were analyzed by the Dow Chemical Company; the results of their analyses are presented in Table 1. The analysis of TCDD found it to be o f greater than 990 purity. * Present address: Perrine Primate Laboratory, EPA, p.o. Box 490, Perrine, FL 33157. 396 TERATOLOGY STUDIES WITH 2 ,4 ,5 - T AND TETRACHLORODIOXIN 397 TABLE 1 C hemical Analysis of A nalytical and T echnical G rade Samples of 2,4,5-T. A nalyses S upplied by D ow C hemical Company Impurities . Quantity of impurities Technical" Analytical TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) 2,5-Dichlorophenoxyacetic acid 2.4-Dichlorophenoxyacetic acid 2.6-Dichlorophenoxyacetic acid 2,3,6-Trichlorophenoxyacetic acid 2,4,6-Trichlorophenoxyacetic acid Bis(2,4,5-trichlorophenoxy) acetic acid 3 Isomers of dichloromethoxyphenoxyacetic acid 2.4,5-Trichlorophenol 0.5 ppm 0.42% 0.05% <0.02% 0.55% <0.1 % 0.4% 2.9% <0.1 % <0.05 ppm <0.1% <0.1 % 0 <0. 1% 0 0 0.2 % 0 ' Dow Lot No. 120449. Three strains of mice and 1 strain of rat were used. The random-bred mouse. CD-I strain, was considered the animal of choice for these studies since it would allow for the Dression of results against a heterogeneous genetic background. To assess results ainst a homozygous genetic background, two inbred strains of mice, DBA/2J and C57B1/6J, were also used. Rats of the CD strain were used. Both the CD-I mice and CD rats were procured from Charles River Laboratories, Wilmington, Massachusetts. The mice of the two inbred strains, DBA/2J and C57B1/6J were procured from the Jackson Laboratories, Bar Harbor, Maine and subsequently mated at the Institute. Detection of a vaginal plug in mice and presence of sperm in vaginal smears from rats indicated day 0 of pregnancy. All animals were primiparous females, housed individually, and allowed free access to food and water. 2.4,5-T and TCDD were administered sc as solutions in 100% (CH ,):SO (dimethyl sulfoxide) in volumes of 100 /ul per mouse for each injection. This procedure was selected since a previous study (Courtney, er al,, 1970) showed that the po or sc route yielded equivalent incidences and types of anomalies. 2.4,5-T was administered to rats by gastric intubation as a suspension in 15% sucrose solution: volumes of 200 /I per rat were used for each administration. TCDD was administered sc to rats in (CH3)2SO in volumes of 100 /I per injection. In all animals, the administration of compounds com menced on day 6 of gestation and continued on a daily basis through day 15 of gestation. CD-I strain mice were killed on day 17 of gestation. C57BI/6J and DBA/2J strains of mice on day 18 of gestation, and CD strain rats on day 20 of gestation. All animals "ere killed by decapitation after which both mother and fetuses were examined grossly. Fetuses were fixed in Bouin solution until necropsied. The following conventions were observed in compiling data. If a fetus was either dead or resorbed, it was regarded as a dead fetus. Only live fetuses were examined for physical abnormalities. A fetus was classified abnormal if it was alive and had at least one type of anomaly (regardless of type). Similarly, a litter was classified as abnormal if it con tained one or more abnormal fetuses. A fetus was said to have abnormal kidneys if at st one of its kidneys was affected In calculating the ratios of liver to body weight in 3 9 8 COURTNEY AND MOORE the mother, maternal body weight was defined as the difference between the weight of the mother on the day it was killed and the gravid uterus weight. Maternal weight gain was defined as the difference in the adjusted maternal weight on the day it was killed and its weight on day 6 o f pregnancy. For statistical analysis, the litter was considered the experimental unit. Five litters or less were considered an insufficient sample size for statistical analysis. Averages were calculated for each litter, then across litters. The Mann Whitney U and chi square tests were used. RESULTS AND COMMENTS The 3 experiments with the CD-I mouse are presented separately so that the experi mental animals could be compared to their respective controls. This was preferred due to slight variations observed in the randombred mouse. Table 2 presents the toxicologic evaluation of 2,4.5-T and TCDD in the pregnant mouse and rat. It had been reported earlier that (CH3):SO was neither toxic nor teratogenic under the conditions of this experimental design (Courtney etal., 1970). The current data confirm this observation. The following results are shown in Table 2. Feta! mortality. 2.4.5-T/tech was fetocidal in the CD-I mouse at a dose of 150 mg/kg which may be close to a maternal toxic dose. At all other doses studied, 2,4,5-T/tech or 2.4.5- T/anal did not affect fetal viability in the mouse. In the rat, there was a significant increase in fetal mortality at a dose of 80 mg/kg. Since this dose was a maternal LD40. the increase in fetal mortality may be related to maternal toxicity. TCDD did not in crease fetal mortality in the mouse or rat at the doses employed. Fetal weight. In all mouse strains, both samples of 2,4,5-T, at 100 mg/kg and greater, significantly reduced fetal weight. The lowest dose of 2,4,5-T, in experiment I with the CD-I mouse, did not affect fetal weight. An apparent dose-related response is seen in this experiment and experiment 3. The reduction in fetal weight is probably a toxic action on the fetus. The administration of 2,4,5-T/tech to rats did not affect fetal weight. TCDD did not significantly affect fetal weight of either mice or rats. Maternal weight gain. Maternal toxicity was evaluated by the maternal weight gain during gestation. In the studies with the C57B1/6J mice, 2,4,5-T/tech produced a significant reduction in maternal weight gain. In all other mouse studies, neither 2.4.5- T/technical. nor 2.4.5-T/analytical, nor TCDD significantly affected maternal weight gain. In the rat. 2.4.5-T/tech caused a reduction in maternal weight gain at the 2 highest dose levels while TCDD was without significant effect. In general, a reduction in maternal weight gain suggests some maternal toxicity. Maternal lit er to.body weight ratio. Both samples of 2,4,5-T caused a significant in crease in the ratio of maternal liver to body weight in all 3 strains of mice. In the CD-I mouse, TCDD did not affect this parameter, but did produce a significant increase in this ratio in the inbred strains of mice. In the rat studies, neither 2,4,5-T nor TCDD af fected this ratio. The significance of liver enlargement due to pesticides has been extensively discussed by Golberg (1966). It is attributed in many cases to a hyperplasia and concomitant increase in the metabolism of pesticides, stimulated or induced by the pesticide itself. In the rat, there was no increase in the ratio o f liver weight to body weight, and the rat does not readily metabolize 2,4,5-T unless it is induced (Courtney, 1970). In contrast, with 2.4,5-T stimulation there was liver enlargement in the mouse. TERATOLOGY STUDIES WITH 2 ,4 ,5-T AND TETRACHLORODIOXIN 2437 Species Compound Dose d Average No i>r y,, ictui lillcrs morliilily/liller Average letal weight <g) X SD M aternal weight gain (g) X SD M aternal liver/body weight x 100 X SD CD-I mouse, random bred l-xpl. 1 DMSO c 2,4,5-T/(ccli 2,4,5-T/lcch 2,4,5-T/lcch l;xpl. 2 DMSO 2,4,5-T/anal TCDD TCDD l-'xpt. 3 DMSO 2,4,5-T/lcch 2,4,5-T/anal 2,4,5-T/anal 2,4,5-T/anal I TCDD DHA/2 mouse, inbred DMSO 2,4,5-T/tech TCDD C57UI/6 mouse, inbred DMSO 2,4,5-T/iech TCDD CD ral, random bred Group 1 Sucrose 2,4,5-T/lecli 2,4,5-T/lcch 2,4,5-T/lcch 2,4,5-T/lcch Group 2 DMSO TCDD a 50 100 150 a 100 1 3 a 100 100 125 100 1 1 a 100 3 a 100 3 a 10 21.5 46.4 80.0 b a 0.5 12 7 3 4 9 9 9 10 8 10 10 9 10 24 II 9 24 15 7 29 10 8 7 4 9 6 6.6 1.35 0.09 2.25 2.00 7.73 0.37 6.6 1.26 0.07 2.87. 1.84 8.22 0.72 7.5 1.00 0.07 4.76 0.89 9.35 0.44 51.7 0.91 0.14 4.14 2.45 10.23 0.67 8.8 1.02 0.20 2.92 1.54 8.06 0.50 9.6 0.73* 0.16 2.97 1.76 9.51 * 0.96 13.6 1.07 0.24 2.44 1.93 7.62 0.95 12.4 0.96 0.24 2.80 1.85 8.54 0.41 8.4 1.09 0.20 3.44 1.86 8.59 1.08 10.7 0.85* 0.13 4.46 2.22 10.18* 0.46 11.6 0.86* 0.17 3.17 2.85 10.53* 1.20 12.9 0.71* 0.25 3.75 4.16 10.99* 0.70 11.8 0.78* 0.11 3.75 1.85 10.69* 0.55 26.1 0.85 0.11 3.82 1.68 8.65 0.64 27.0 0.67* 0.10 2.37 >2.15 9.72* 0.78 27.0 0.89 0.13 3.97 '1.89 9.15* 0.38 10.8 0.99 0.09 3.35 1.48 8.00 0.60 15.9 0.75* 0.12 1.67* 1.68 10.39* 1.00 5.3 1.05 0.16 3.25 1.27 9.31* 0.30 3.4 2.48 0.25 65.56 11.56 5.17 0.36 1.8 2.40 0.38 61.13 11.44 5.23 0.39 1.4 2.54 0.20 63.83 9.19 5.04 0.25 3.8 2.20 0.42 43.21* 19.80 5.29 0.48 52.1 2.30 0.20 27.25 25.17 5.95* 0.31 0.0 2.44 0.05 69.70 13.15 5.35 0.39 3.0 2.41 0.17 57.96 10.12 5.65 0.45 * Abbreviations: a -= IOO/>l/animal;b maternal Ll)4(); * /> 0.05;c ; dimethyl sulfoxide; d - TCD D expressed as /ig/kg; 2,4,5-T expressed as mg/kg. uvO< VO 4 0 0 COURTNEY AND MOORE and the mouse does show an increase in microsomal drug metabolism (unpublished data). Cleft palate. The teratogenic evaluation of 2.4.5-T and TCDD is presented inTahle Both samples of 2.4.5-T produced cleft palate in all 3 mouse strains. A dose-related response is suggestive in the CD-I mouse with 2.4.5-T/tech in experiment 1 and is apparent in experiment 3 with 2,4.5-T/anal. Also, in experiment 3, both samples of 2.4.5- T at 100 mg/kg were equivalent in response since the number of litters affected and the incidence of cleft palate in these litters were essentially the same. TCDD also produced cleft palate in all 3 strains of mice. In experiment 2, with the randombred mouse. TCDD was studied at 2 dose levels. At the lower dose level. I /xg/kg. only I litter had fetuses with cleft palate, while at the 3 g/kg dose, 3 out of 10 litters had fetuses with cleft palate. Also, in experiment 3, TCDD was combined with 2.4.5- T/anal to determine whether the response of 1 compound was affected by the presence of the otherr Cleft palates were produced by the combination but there ap peared to be no potentiation of the teratogenic effect. Neither 2,4.5-T nor TCDD produced cleft palate in the rat fetuses. An additional study was undertaken to evaluate the possibility that 2,4,5-T could cause cleft palate in the rat. Nine rats received 2.4.5-T/tech. 150 mg/kg, sc on days 13 and 14 of gestation, the time of palate closure. This is the maximum dose which could be tolerated for 2 days and not cause maternal mortality. No cleft palates were observed in these fetuses; how ever. there was an increase in fetal mortality (14%) which was statistically significant compared to the control value (0 %). Kidney anomalies. The other r.nomaly to be considered in these studies involves the kidney. All kidneys were sliced open and examined grossly. The anomalies obsened could be described as unilocular cystinephrotic kidney as well as hydronephrosis of all gradations. Histopathologic studies are under way to clearly define the renal malforma tions. Until further definition is accomplished, all types of kidney malformations arc simply tallied as kidney anomalies. As can be seen from the 3 experiments with the CD-I mouse, the incidence of renal anomalies in the control animals varied. In the first experiment no kidney malforma tions were observed, whereas in the second and third experiments there was a low incidence which may be considered normal for this strain. The 2 inbred strains also had a low background incidence of kidney anomalies. In experiment 1with the CD-I mouse, 2,4.5-T/tech did not affect kidney development. In the fetuses from mice treated with 2.4,5-T/anal, 100 mg/kg (experiments 2 and 3). there was an increase in the incidence of litters affected and also in the average number of fetuses in these litters displaying kidney malformations. Administration of 2,4.5-T tech did not produce as great a response. In the studies with the inbred strains of mice. 2.4.5- T/tech did not increase in the incidence of kidney anomalies relative to the control values. Treatment with TCDD produced a marked increase in the incidence of kidney anomalies in all mice strains, and a dose-related response is evident in experiment 2 with the CD-I mouse. There was no potentiation of the response when 2,4,5-T/anal was administered in combination with TCDD. The mouse studies showed that the C57B1 '6J mouse was the most sensitive strain to TCDD-induced effects in that almost 100 %ofthe fetuses displayed kidney anomalies. TERATOLOGY STUDIES WITH 2 ,4 ,5-T AND TETRa CHLORODIOXIN / N . <i>J Ni *1 I ' l l r I r . M . M l - N M l K i i i m > \ M . M A I I I S I N * , - | ,, V | A tN. I I ' I l ' I J I >- I 141 A I I I I M t I A N I I | ( A I \ H Cicli palnlcs Kidney unomalics Species Compound Dose d No. Av. No. No. Av. No. No. live Av. No. live fillers clef! palates lillers affected fetuses lillers fclus/liller aHeeled in alTecIed lillers affected in affected litters Mouse CD-I, random bred IZxpt. 1 DMSOc 2,4,5-T/Iech 2,4,5-T/Iech a 12 11.8 0 50 7 12.0 0 100 3 11.7 1 0 0 3.0 00 00 00 2,4,5-T/lech 150 3 9.0 3 5.3 00 l-Jxpl. 2 DMSO 2,4,5-T/unal TCDD TCDD a <7 11.4 0 0 3 1.0 100 9 11.8 8 4.4 7 1.7 1 9 9.4 1 2.0 5 4.6 3 10 10.4 3 1.0 10 6.5 Ivpl. 3 DMSO a 8 11.3 0 0 5 2.0 2,4,5-T/lecli 100 10 10.4 4 2.0 8 2.4 2,4,5-T/anal 100 10 9.8 4 2.0 10 4.2 2,4,5-T/unal 125 9 9.7 7 5.4 6 4.-1 2,4,5-T/anal I TCDD 100 1 1 10 10.9 4 3.3 8 5.3- DHA/2J. inbred DMSO 2,4,5-T/Iech TCDD a 23 5.1 0 100 11 3.7 3 3 9 6.1 2 0 1.0 1.0 3 1.0 1 1.0 8 1.8 C57HI/6J, inbred DMSO 2,4,5-T/lech TCDD a 23 7.2 0 100 15 6.7 6 3 7 8.3 5 0 1.2 2.6 2 1.0 00 7 8.0 Rat CD random bred Sucrose 2,4,5-T/lech 2,4,5-T/lech 2,4,5-T/lech 2,4,5-T/lech 29 9.3 0 10 10 10.2 0 21.5 . 8 10.6 0 46.4 7 8.9 0 80 b 2 12.5 0 0 0 0 0 0 00 2 1.0 3 1.3 1 2.0 1 4.0 DMSO TCDD a 9 11.6 0 0.5 6 8.0 0 0 0 00 4 1.8 * Key lo tellers: :i 100 /l/animal; b --inalcrmil l-f>40; c dimclhyl sulfoxide; d T C P D expressed as /jg/kg; 2,4,5-T expressed us mg/kg. Kp <P JN ro CO CD 4 0 2 COURTNEY AND MOORE In ihe rat. 2.4.5-T tech produced a minima! response in kidney me TCDD produced a slightly greater response: therefore, additional st taken in the rat to evaluate the effect of TCDD on kidney developi administered on days 9 and 10 (6 rats) or days 13 and 14 (8 rats) of ges 2 fig/kg, in (CHj):SOsc. In the control rats, there were no fetuses with as compared to an 11 % incidence from treatment with TCDD on da; 34% incidence from treatment on days 13 and 14. Thus, it appears that kidney development in the rat fetus. In these studies, no cleft palates the control or experimental fetuses. Some sources of species and strain differences in teratology have b Baker et al. (1970) and Smithberg (1967); however, until the mechan 2.4.5- T or any other teratogen is more fully understood, it is difficult tc cause or causes to the difference in species response. Currently, the feta 2.4.5- T is being studied in the mouse and rat to see whether this might the difference in response of these 2 species. Other anomalies. A few additional types of anomalies were observed and rats. In general, the type and incidence of these anomalies wen. control and experimental animals. Also, in this study, 2 very mild hemorrhagic gastrointestinal tracts wer. from 2.4,5-T treated rats and 6 hemorrhagic gastrointestinal tracts i TCDD treated rats. Hemorrhagic gastrointestinal tracts are probably c of toxicity as opposed to a malformation. In this case, the toxicity is mos on the fetus as opposed to maternal toxicity being reflected in the fea Postnatal study. In order to confirm that 2,4,5-T was not teratogenic in natal study was undertaken. Eight pregnant rats were administered 50 mg/kg, po, in sucrose from day 6 through 15 of gestation. Seven contrc 0.2 ml sucrose. All rats were allowed to litter. The neonates were examine, on day 1 and twice weekly thereafter until sacrificed on day 21. Litter size the 2.4,5-T/anai treated litters were comparable to the controls at all tin was less than I % in both groups. The weight gain for the 3 wk period v> both groups. Eye opening occurred on days 13 and 14 for all neonates, boi controls. Thus, under the conditions of these experiments, 2,4,5-T is not t this strain of rat and prenatal administration does not impair postnatal development. ACKNOWLEDGMENTS The authors gratefully acknowledge the assistance of Mrs. J. Putnam, Mr Mrs. M. Harris, and Mr. M. Riley. The statistical analyses were performed by Di M. Hogan, and J. Haseman. The authors thank Dow Chemical Company for thei in supplying the chemicals and the analyses. REFERENCES A llen, J. R., and Carstens, L. A. (1967). Light and electron microscopic ob: Macaca mulatto monkey fed toxic fat. Amer. J. Vet. Res. 28, 1513-1526. Audus, L. J. (1964). The Physiology and Biochemistry of Herbicides. Academic York. Baker, S. B. de C., and D avey, D. G. (1970). The predictive value for man of tests of drugs in laboratory animals. Brit. Med. Bull. 26, 208-218. O - 0-651 2441 o a.S3 '.'utahon Research. 21 (10731 33.S-.34 Elsevier Scirntmc Publishing C om ian v. Amsterdam - Printed in The Netherlands 335 LYMPHOCYTE CHROMOSOME ANALYSIS OF AGRICULTURAL WORKERS DURING EXTENSIVE OCCUPATIONAL EXPOSURE TO PESTICIDES' JI LIE VnDP.K. MICHAKL W A T.'i'N i m . W \V HENSON Environmental Protection Acencw Idaho State D>hartnu nt >>l Environmental and ( otnmuntlv .'vices. Boise. IdanSj7-'&' f 5 A.) Received March ist. 10731 Revision received June 4th. 10-3; SUMMARY Lvmpliocyte cultures from 42 pesticide applicators and i*> controls were -crutinized for chromosomal aberrations during tlie midwinter ebb in pesticide -praying operations. and again durine the peak summer period of intense .-praying activity. Cultures prepared fr-m the exposed individuals during the heavy -praying period showed a market: nv tease in the frequence of chromatid lesion-. This trend wa- r-peciallv noth i-abic .:m"i-,g worker.- vxpo-od primarily t" herbn ide- A h-w chromatid exchange neurt- were a lso noted among the exposed group. Al-o di- u~-vd is the need for better method.- of e-uniating the potential mutagenic threat, if any. of such observed clastogenicity. INTRODUCTION The Idaho Community Study on Pesticides is one of thirteen similar research facilities throughout the United States in areas where pesticides are extensively used. Sponsored by the Environmental Protection Agency, the primary task of this unitied investigative effort is to evaluate the effects of pesticide exposure on human health. The Idaho program is now in its sixth year of intense clinical, biochemical and epidemio logical scrutiny of a core group of carefully selected volunteers having extreme occupational exposure to various pesticides. An additional parameter currently being examined in detail i.- the possibility of using cytogenii analv.-is ol lymphocyte chro mosomes as an index of pesticide mutagenicity in man. Cytogenetic analvsi- of chromosomal aberrations in somatic cell cultures is oiu of the major methods of te-ring currentlv recommended f<>r evaluating chemical mutagenesis in mammalian svstem-'-n " Most investigator- agree that tin. dominant lethal test and the host-mediated as-ay are al-o important te-t procedures, and that Thi* iVM-.ircti \\.1* in-; mull: t i.:rm.i - o U ; 1> :!i* I' . *i* i. *i I* ' i >umk* :sn 1\;: *I'r-n - I ir;*v.i..iI \ . ' h ' 1 if'* Ici-.h* r.* i r m.i. ` ***m fVz?/ 9 3 3 6 J. YODER et al. all three should be utilized in confirming mutagenicity in mammals. However, the latter two techniques are not suited for use with human subjects, and somatic cell cultures thus remain the only practical method of assaying morphological evidence of apparent damage to the human genetic material, per sc. With respect to such cultures, mi : r:o techniques are preferred over in vitro tests because they provide the added advantage of taking metabolism into account*'13. Although such an approach by itself cannot provide unassailable proof of concurrent gametic involvement, it appears likely that autosomal aberrations mav indicate parallel gonosomal events uf a similar nature14. Even as a purely somatic indicator, analysis of lymphocyte chromo somes would seem highly pertinent when one considers that many spontaneously occurring diseases, certain neoplasms included, are now believed to be caused bi environmental pollutants3. The tremendous array of agricultural xenobiotics now in common use consti tutes a large portion of the various chemical agents to which man is environmentally exposed. The indiscriminate use of such substances would logically present the pos sibility of a genetic legacy of increased mutation frequency and subsequent human hazard. Increased aberrations of lymphocyte chromosomes have been recently re poned' in a group of Michigan fruit producers involved in heavy pesticide spraying. Accordingly, we have examined chromosomes of peripheral lymphocytes (leukocyte.-1 cultured from persons selected from our occupationally exposed study group. Tinprevalence of chromatid lesions among these volunteers has then been compared with that of a control group, both prior to and during the heavy spray season. MATERIALS AND METHODS It was initially hoped that -unicient numbers of persons having exclusive pational exposure to a single chemical cries could be obtained. However, because of tiie great agricultural diversity of this region, such a sampling technique proved to be impossible. Within Canyon County alone, in which most of the exposed participants reside, more than one million pounds of pesticides were applied to crops during 1072 (ref. 10). This figure, irrespective of other agricultural chemicals such as fertilizers, amounts to approx. 4 pounds of pesticides for each acre of farmland. Persons highly exposed to pesticides in this area usually apply a large variety of chemicals throughout the growing season, and multiple exposure is the rule rather than the exception. For these reasons, dose or duration of exposure is another variable that cannot be rigidly defined by such an approach. Because of their local prevalence in pesticide-related occupations, only male Caucasians were sampled. Persons with recent histories of viral infections, chc-mothtrapy or X-ray treatment were rejected, as were those with histories of malignan cies. A total of 16 control and 42 exposed persons, matched as closely as possible as to ages and physical characteristics, were chosen. High exposure was defined as spraying with pesticides for at least 4 h per day on three or more days per week throughout the peak spray sea.-on of June 15th through August 30th. The control group was cumposed of businessman, students, health professional.' and teachers who had no history of involvement with pesticides. Ages n i the control group ranged from 10 to 04 imean yi.S). Persons in the exposed group ranged in age from ib to 70 mean 3S ri1 and had from 1 to 25 y ea rs (mean b.v of prior occupational exposure to pesticides. A s show:: TABI.K 1 I'ESTICIOF.S MOST COMMONLY l ORDER OF FRfcCEMY (ilullp .-I /"Ucticidr-r.x f>"si d j ( 'W H iftii n a im 1'elllelUIl / '. r . ' 'll' ( l.ihvl parathimi ( >l' j Trichlornfoii <d ' ! Naled <i]J Malathion I* Dicoiol <i f Diazmon (if Endosulfan ` >C DNOC I'H Methyl parathion <>P Toxaphcne <if iMmcthoatc <'P PUT n , Phlordimcform <'(. ilxvclcmetor.mcthvl i ip J TEPP t'P * Carbaryl C 1 Nomenclature alter Here" a:v; It '' OP. organic pho-i-hor-u- .?. -cries. in Table I. person- m tin- xp accordance with their pn. i-r, . age. 42.3 : mean years of nri t spray rig operators and farmerchemicals most frequently di-p- pounds demeton. ethyl parathi"; i applied less frequently by the gr 3.5 ; mean years of prior agrien of local weed control agencies. I herbicides; especially 2.4-D. am. 1 Blood samples (to ml !,. ] during the off-season, Januaryi pationally exposed for a period j ohtained front all persons durum ' the peak season of pesticide ule : dailv exposure among the agn- . extensivelv prior to both -an.: fullv noted. j Lymphocyte culture- werkit- (Difco Laboratories. DiU-c: prcviouslv report- d by M>>kh: proceduic was to increase meu: facilitate the tek htliijUe. The -.it mitotic divi-|oii hi order to ;u;: 9 -/0 4 2443 /HD J. YODER et al. mammals. However, thr bjects, and somatic cell morphological evH],.nr,. - st . With respect to because they prov ide the l_ chough such an appro, , gametic involvement, p .irailel gonosomal event? of ysit of lymphocyte chrom,,. that many spontaneously believed to be caused bv -. w in common use constj. :r. man is environmentally : .?ically present the p..*. -. y and subsequent human have been recently rer heavy pesticide spravinc. .. lymphocytes fleukocyt,-.. r'-r-.^ed study group. Th. :r.-r. been compared v\itI. rav season. r - having exclusive i.r, u. r.r:. However, becau?e ,,f technique proved to be .e exposed participant? :hrd to crops during 1972 trucis such as fertilizers, farmland. Persons highly v of chemicals throughout :r than the exception. For ,: 1t that cannot be rigidly :upations, oniy male : vrai infections, cliem- histories of malignan- h ?elv as possible as to a- w. defined as spraying - Ter week throughout the -.:t -1 croup was eom- ;.7t- who had no history -jr: from 19 to 04 (mean .. mean 3S.0 : and had t t -onde? A- PE5TTCIDES AND CHROMOSOMAL ABERRATIONS 337 TABLE 1 I'ESTICIDES most commonly creo bv exposed slbjf.ctr in this stud y * (listed in decreasing T (RL'ER OF FRRgi'ENCYl ; ,a ur A 11 1t.i.`-.:iCldr-C\-pnX( (i Group t Hrrbicidt -r.p-jsra i (. `Himmi natnc Z Imelon i 1 thv! parathion Trichlorofon . Naied Malathion | IMCOIoi 1 Piazinon I Endosulfan l PNOC Methvl parathion 1 uxaobene panethoate PPT 1 hlordimeform - (iNvdemctonmethvI TEPP larbarvl T vf>cl} up OP np ( >P OP nc OP oc TH OP OC ( iP f *c oc OP ()P C Ciuumnn nanu - a -L> Amitrole Atrazint Zmcb (fumnude DC PA Dicamba Chlorpropham Alachlor Metiram Ifuneicidci Tnfluralin Maneb . fundarle Picloram Diquat 2.4.3-T Nomenclature alter Bure2 and !'rear* u n p . orame phosphorous scries <'0 . organic chlnnnc < TIC* C. carbam ate T a b le 1. p erson ? in tile e x p o se d g r o u p w e re fu: .no :dance with their predominant type of occupational exposure. Group A :nican act. 4 2 .3 . mean year? of prior exposure. 12.01 consisted of l b cropdusters. formulators. spray rig operators and farmers who were chiefly exposed to insecticides. The specific chemicals most frequently dispersed by Group A were the organic phosphorou? com pounds demeton, ethyl parathion, trichlorofon and naled. These and other insecticides applied less frequently by the group are summarized in Table I. Group B (mean age. 30.5 ; mean years of prior agricultural exposure, 6.3) was comprised of 26 employees of local weed control agencies. These persons were all predominantly exposed to herbicides; especially 2,4-D, amitrole and atrazme (Table I). Blood samples (10 ml heparinized) were first obtained from all volunteers during the off-season. January-February, 1071. when none of them had been occu pationally exposed for a period of at least 30 days. A second blood sample was then obtained from all persons during the period of July through August, which is well into the peak season of pesticide application and represents a common interval of intense daily exposure among the agricultural workers ?vlected. Each person wa? interviewed extensively prior to both samplings and all pesticide-related information was care fully noted. Lymphocyte cultures were prepared by mean? of Difc<> TC chromosome culture kits Difco Laboratories, Detroit. Michigam. The technique i? ba?ed on the procedure previously reported by Mo o r h ea d ct al.1-. Our only modification of their standard procedure was to increase incubation temperature from 37: to 3S . which ?tcmvd to :.d dilate the tviImiqui . The ?amplc? w e n .uitun-d for 4> h obtain cell? in tin nr?t n.ii- ti division in .,rder to minimize the v u n n h iiitv m aberration vivid that 1- - 'iin .- k 2444 3 3 8 J. YODER ct al. tinn-s as-opiated with longer culture times'. Flame-dried slides were stained with fiiem>a and rearranged and coded by a person other than the scorer to avoid bias 25 metaphasc spreads inmi each person were then examined microscopically fr,r vliromosomai aberrations. Only karyntypable cells having widespread chromatidwit!) minimal overlapping were selected for scoring. Photographs were made .f u|| abnormal metaphase rieurcs and karyotvping wa- performed whenever there ap peared to be evidence of obvious chromosomal rearrangement. The criteria of Glhh a r i>t t "ere followed in the determination o f chromatid achromatic lesions gap-, breaks and chromatid exchange ffgures. KESLLTS AND DI5CYSSI0N Other than random loss of chromosomes, heteroploidy was not demonstrated in any of the 1450 mitotic bursts examined. With respect to chromosomal lesions. the majority of achromatic areas gaps] and breaks were confined to single chromatid.-. Although iv-chromatid lesions were occasionally encountered in both control and exposed individuals, this apparent trend toward chromatid aberrations rather than chromosome aberrations would appear to merit further study. The incidence of chromatid lesions on a per person basis is presented in Table II. The mean number of gaps and breaks per person per 25 cells examined did not appreciably change for the control group at cither sampling period. Among the cxp-'-ed group, however, the mean number of gaps per person nearlv doubled in i-ul- T \ 1: i . l . !I .-f w . . \ \ l v ak: \ t :.' <*.t .TRFEN-: ' >F . HK'tM \ t:; LI. 1NS ' i i 'll f* A .ini ht; T `-r Chrowat.ti ( )ff->CU r 1 5 ,. i } Chnmmf.il .W.i/ Si d.`.UI -- :tiki M id j - ControlTotal exposed 10 4- (Iroup A 16 11nsectJCiJc-expo^ccl: 1O Group B 26 Herbicide-exposed l Mean = S.E. Ranee Mean --s.E Ranee 0.63 -- 0 22 0.62 --0 11 0-2 Mean --S.E. 1.00 -- 0.22 Ranee 0-2 Mean --S.E. 0.*S --0.10 Ranee O--1 01` A II O j %4 O 09 = 0 : 4 114 --0 1 7 O-5 0 75 = 0.27 0-3 1.1$ 0-5 0 3 1 --0.12 0--I 0. r 7 --o.oS 0-2 0 31 = 0.18 0-2 0.0; --0.0s 0 --1 0 4 4 --0 22 0-3 I . 71 --0.24 0-6 1.50 - 0 :g 0-3 1 Si = 35 0-6 tures from the midsummer samples, and the mean number of breaks ub-erved per person increased bv a factor of to. The maximum number of gaps found in any single exposed individual .Table II) increased from 2 in the slack season cultures to 5 in the midseason cultures. Maximum breaks for any single exposed volunteer rose from 2 t>0 during the same period. (Different persons were involved in each of the four ca.-es cited.1' Tin --- r\po-i J primarily t" insecticides iGroup A; exhibited a 25"., reduction in the mean number of gaps per person in cultures from the high exposure permcl. However, the mean number of breaks increased 5-fold in these same samples. Members "l the group ireoueiitlv involved with herbicide .-'laying ;tir<up B `. showed an it.- PESTICIDES AND CHROMOSOMAL ABERR. crease of nearlv 4 times the mean mini season. Mean break' per iXT-m |.,r ,, period (Table 111. A lso notcw>rti.v 1- ; breaks, rcspcctivelv. during the big:. .. exposed eroup. On tile otiicr hand, : 1 noted in Group B workers during b { bility of induced compensatory pr. : lianced chromosomal repair. 1 During the July-Augu-t - rn cells examined), a small number : | included one Group A quadriradial. ya and a possible Group G tnradiai. Sm | general population at a frequence -: j in our exposed group approaches ..1; any of these configurations, but uni were sampled in the control er.u; 11 version in the A 2 chromosome Tinj pear in any of the other 25 cells - : From these results, it is damage in lymphocyte cultures greater durinc the heavy ~prav - .ever, the pc-sihilitv oi i-w u m . nt : lative. Because >f the trenn-i!-i"-.ithc direct plmiotypi. survcT.!..:: retrospective t--c!imque- ' m- -0 existing i,"'.iiih -tati-ti' -. I compiled with the geiu ti' i-t n. 1 incidence of such parameter- m- -' ilasms. !c.. among agrn uitur.d \\ because of insufficient data. On a estimate mutagemcitv in suspected view techniques. However, a maj-r researcher and subject. REFERENCES 1 R e n p f r . M A . e s u I C ['.a:- h u m a n pe ripiurai iiu k c c v li 2 H e r o , (j L L . l . F a 0 1. O'- j kr-TFis ' s foiur:-; o: chcil.:* .. 4 l . r s T K J Y s s .1 ' . ; . M s 1.1 ' . ` - M 11 . c .im linU c.. M..-- . i " ` : : ^ l-.v.ws H J IcmHil.c."[: ]`Ricr. sM' 1` Lrt l.J- H.'im.i 11170 pp 1011-202 o F rf. \ k I) F. H !'i i f , / c.7 4" ; (. i.inRi'T li .Tie tn..:m> :n l\ 1-K1.' Ks l.il- e > ..1 i s l . L i . H i R i K . Mu'.ii:' ::ii.v. - u:.: ' l'|-4 I-(I-', 2445 J- v o d e r ri al - ''d e s w e r e s t a i n e d wjt|, sm rer to avoid h i^ .ined microscopic a ||v f g w i d e s p r e a d elir<iu.iti,j. g r a p h s w e r e m a d e <.( a || :n ed w h e n e v e r there ap. e n t. T h e c riteria of r,, c h r o m a t i c l e s io n s , cruj iy was not demonstrat-.j to chromosomal le-i,,n. fined to single chromatid, .-red in both control and 1 aberrations rather than .dy. .isis is presented in Tal-i, .'5 cell.- examined did i g period. Among t|.. ,.v n nearly d'.uhk.i . if i eri j ''hrom aiid breaks fi- season M id- O 3! = 0.1 2 0 -1 0 1 7 -- 0.0$ 0-2 0 3 1 -- 0.1S 0-2 0 0 7 - 0 05 o-I <M4 0-3 I TI T 0 1 ( 0-0 1 . 5 6 - 0 4 t) 0-3 r > i = 0 33 o-< r i>i breaks observed per i gaps found in anv single -eason cultures to 5 in the 1volunteer rose from 2 to in each of the four cases \hihited a reduction the high exposure pi riot], 'unn. dimples. Member- <IriUIB -hoUtd IV- PESTICIDES AND CHROMOSOMAL ABERRATIONS 3 3 (l i crease of nearly 4 times the mean number of gaps per person during the peak spraying | -eason. Mean breaks per person for Group B increased by a factor of 25 during this , period (Table 11). Also noteworthy is that the two subjects having the most gap- and breaks, rcspcctivelv, during the high exposure period were members of the herbicide; exposed group. On the other hand, the markedly low frequency of breaks (0.07 - m iji $ noted in Group B workers during the slack -eason invites speculation as to the po-si| hilitv of induced compensatory protection occurring at this time in the form of en* danced chromosomal repair. * During the July-August scoring of the 42 highly exposed individuals (1050 | cells examined), a small number of chromatid exchange figures were noted. These I included one Group A quadriradial. two Group C triradials. two Group F quadriradials ; and a possible Group G triradial. Such interchanges have been found to occur in the i general population at a frequency of about one per 3000 cells4. The frequency noted in our exposed group approaches one per 200 cells. None of the controls exhibited any of these configurations, but. unfortunately, fewer individuals (400 cells examined! . were sampled in the control group. One exposed individual also had a pericentric inj version in the A 2 chromosome. This was confirmed by karyotyping but did not ap pear in any of the other 25 cells scored for that person. From these results, it is apparent that the extent of visible chromosomal damage in lymphocyte cultures prepared from the exposed group is considerably greater during the heavy spray -eason. Without additional correlative studie-. how ever. the possibility- uf concurrent mutagenic involvement must remain only specu lative Because of the trememiou- limiting actors imposed by long generation times, tiie direct phenotypic surveillance ot human populations is restricted t**onlv a lew retrospective techniques. One such method would logicallv include the analysis of existing health statistics. Unfortunately, contemporary vital records are not usually compiled with the geneticist in mind. We have recently attempted to examine the incidence of such parameters as stillbirths, teratisms, retardation etiologies, n e o plasms, tc., among agricultural workers in this state, and have had little success because of insufficient data. On a more personal level, another aid in seeking to estimate mutagenicity in suspected populations is the large scale use of detailed inter view techniques. However, a major obstacle here is the extent of credibility between I researcher and subject. l j REFERENCES 1 B e n d e r ,M. A., a n d J. C>. B r e m e n .Facto rs influencing chrom osom e a b erra tio n yield- in the ' h u m an pe riphe ral leukoc yte system. Mutatu m h'is . s iooqi 4 B erg. G. L lE d.l. F a rm Chttm ca is Handbook Meister W illoughbv. Ohio. 1073 3 E p s t e in . S. S.. Control of chemical pollutants S a t u r e . 4 4 ' .10701 m o - m o 4 E p st e in , s . 5 .. a n d M. S. L egato r, in The M n;j<;em:it\ a y Pe sticides. C - m o ftt> ami h i .Tmate-n. M.I.T., C a m bridc c. Mass.. 1071. p. 47. 3 E vans, H. J.. P o p u la tio n cvtogcnetics a nd env iro n m en tal factors, in P. A J acobs. \V. H P rice a n d IV L a w (E ds . H u m an P-epulatian L vt.-a 11, ' ,cs. W illia m s a n d Wilkin- P.dliiiion. io"o pp 100-404. o F reak. I > K H . I',stic: di Ji:,ie\ 4th cd.. College Science Pu blish ers. S t a le College. Pa . 101.0 7 CiErhakdt. K.. T h e t r e a tm e n t of h u m an chromosome* . >1 ; i//a. results in I' VuCKL .and c, K-.KRliORN lE d s .. (.hemcat Mnta c. 10 os :n Mamma:.- ami M a n . Springer. New York 10-0 - 1 . - n iR DT K M i n a g e m t a l - i i i i ; . r -u c 'm ir .e e " an ii.e :.- h lic h e ii /.i i i k u l u i r e : ; > i 1 '.<"4 I 4( ! 44 I y H o o pin g aRNER. R.. a s h A. \V B l o o m e r . L vm p h o c yu - chromosome analvsi* of pv>ti<rti|l. exposed individuals. Intern. Cone Plant Protection Parts, 7 '.1970) 772. to Idaho Community Study on Pestindos. Annual Contract Progress Report. Jdaho Department of Agriculture, 2120 W a r m sp rin g s Avenue. Boise. Idaho 83702. Decem ber j e t h . 1072. pp , ( 11 Ma l lin g . H. \ . Monitoring of chemical mutagens in our e nvironm ent, in H E S ctton M I H arris [ E d s . 1, M uta ge nic Ettrets o f Environm en ta l Contamina nts. Acad emic PresYork. 1972. pp 27-39. 12 Mo o r h e a d . P S . P. C N o w e l l . W I M e l l m a x . D M B a tt ip s a n d D A. H i n o f .r k i k ,. Chromosome preparations of leukocytes cultured from hum an peripheral blood. E.ipt; Res.. 20 ilQbO' 013-610. 13 N ich ols. W V .. P. Mo o rh e a d a n d G. B r e w e n . Ch romosome methodolog ies in m u ta tio n testing. E M S S'cxsletter. 5 11071. 20-23 14 R o h rb o rn . G.. Possibilities of routine 1 c im m u tag en icity tes tinp in m am mals, ,-treh Toxtkol.. 28(1071) I 2 0 - I 2 B . Mutation Research. 21 (1073; 341-14 r KIscvicr Scientific Publishing Corr SHORT COMMUNICATI Lack of mutagenicity of th Cyclamate. a commonly rabbits. dogs and man. althouc place. CHA and N'-OH-CHA a: to be a considerable individual is an indication that the amour tration. Cyciamate has been foui cytogenetic assay systems it: mutations to S-azaeuanme res CHA on chromosome breakacin vivo are contradictory1"-18. > I Chinese hamster bone marrow N-OH-CHA failed to induce an larlv negative in a liost-mediat implantation loss in rats1-' ait: t mations was detected18. In m: but did not induce dominant : In view of the c<>niiictiu. regardine the use of r y d a m . i t vriects nf the cydamate met..: constitution R i i j s . y B y Y -a concentrations raneing ir mi from the tirst larval instar to t substance (o.oi-o.20 0). Folio' < two or three females of the denoted (b) where mass matins I! the males were mated for 6 sue cell stages, whereas in the feedi for a penod of 5 days. The i translocations were scored Chemical damn. i generations and becom-.chemical mutagens is. tliert i- r of MXNG have even been lour tests for sex-linked r e c e iv e detect mosaic letliaU. For dot: In Tables I and II the ti lt can be seen that the trc'iueluding pontmeimic A. B. Cu larval feeding. Although the n Alii>r>-\ i.m.iiv- l l l \ cvci.-lu. - \ i i i r l h v l - A li'.irii-.V-iinri.-- i2-.:.i. 2447 4 -//J ^ ? 3 / cp? 3 .1 'O CYTOGENETIC EFFECT OF THE HERBICIDE 2,4-D ON HUMAN AND ANIMAL CHROMOSOMES M. A. PlUnskaya Tsitologiya 1 Genetlka, Vol. 8 , No. 3, pp. 202-206, 1974 UDC 615-- 099-- 056.7 Introduction. Certain pesticides can make a definite contribution to Induced mutation In man. Identification of those pesticides that are potential mutagens, whose accumulation In various environmental objects can present a genetic hazard not only to individuals but also to the population as a whole, Is therefore an especially pressing task. From this standpoint, It is wise to Investigate the mutagenic activity of widely used herbicides of the 2,4-D group (chlorophenoxy derivatives). The cytogenetic action of chlorinated phenoxy acid derivatives has been investigated principally for various plants [1-5]. Some members of the chlorophenoxy series have recently been studied In Insects and mammals [6-8 ], The present Investigation was conducted to Investigate the cytogenetic effect of one-^ preparation in this group, 2,U-dlchlorophenoxyacetic acid (2,4-D) on human somatic cells in vitro and mouse cells lr. vivo. This herbicide was selected from the rather extensive chlorophenoxy acid group because residues of any preparation of this type in plants essentially consist of 2 ,i-D [?]. Experimental subjects and method. The in vitro experiments were conducted with blood^' from two clinically healthy donors with normal karyotypes, who had not been exposed to aaji> factor capable of affecting the aberration frequency. The lymphocytes were cultured and chromosome preparations made up by the method described in the literature [10]. The 2,4-0.; was added to the culture 3 h after incubation was begun and exposure was continued to the^ end of the Incubation period. *' The in vivo experiments were ejnuucted with unpvuigrvi. 1 mule white mice weighing 18-20 g. Chromosome preparations were-made up from bone-marrow ceils by the method customarily employed in our laboratory [11]. The 2,4-D was administered orally with milk In a single dose. The animals were killed by decapitation 20 h after administration of the herbicide. The chromosome analysis was carried out by the method described previously [10]. The uniformity of the experiments with respect to the aberrant-cell frequency was checked by the method. No significant differences (P > 0.1) were ooserved in the experimental duplications, so the results of the duplicate experiments were summed. The statistical reliability of the differences between the experimental and control variant* and between different dosages was determined by the <p method [12]. Experimental results and discussion. The cytogenetic activity of 2,4-d In a human lymphocyte culture was studied with concentrations having a cytotoxic effect (50 and 20 ug/J and concentrations not having a cytotoxic effect (2.0, 0.2, 0.02, and 0.002 ug/ml). The. obtained In chromosome analysis of cultures treated with different dosages of 2,4-D are given in Tables 1 and 2. It can be seen from Table 1 that the number of aberrant metaphases differed rellab from the spor.tur.'.-ouz 1 f ...1 m*. ` t '.'went (? < 0 .001, P < 0.05). An Increase in the 2,4-D concentration in tnc- culture to more tnan 0.2 was not accompanied by a reliable Increase in the numoer of aberrant metaphases (P > although there was a tendency for the maximum cytogenetic effect to occur at a dose of 2.0 ug/ml. Large doses of the preparation, which had a cytotoxic action on the culture, obviously caused some of the aberrant cells to die or retaraed their entry into mitosis, so that the total number of aberrations remained constant. A decrease in the herbicide 6 2450 concentration In the culture (starting at 0.2 ug/ml) caused a decrease In the number o damaged cells. The data obtained did not make It possible to evaluate the dependence * dosage over the range tested. lan o: Sgonads, 1 its ter Aberrations of both the chromatid and chromosome types developed under the action the 2.U-D, In a ratio of U : 1 (Table 1). Single acentric fragments predominated among' the chromatid rearrangements. At the minimum preparation concentration, symmetric 45 chromatid exchanges were observed In three metaphases ( F i g . 1 ) , i . e . , this 2 , 4- D concentration was not "Ineffective," as it would have seemed if the abnormality spectrui were not evaluated. The chromosome aberrations were principally paired acentric fragment It can be seen from Table 2 that the identified breaks were distributed randomly ov the chromosome groups (P > 0.05). However, the damage was not uniformly distributed o t h c the chromosome arms: 8l.iJ of the breaks were localized in the long arms. The maximum ^ number of abnormalities occurred In the telomeric third of the long and short arms (70 c? and 7*1.3J ) Table 2 Distribution of Number of Breaks Caused by 2,*t-D Over Chromosome Groups C h fn m o tu M i irw upi 2,4-D (O M M U IIIM , A-t A-2 * 3 It C L> F G J-r total # Fbeitg*.* chro: ug. 5 0 .0 0 0 JO.OOO 2 .0 0 0 0 .2 0 0 0 .0 2 0 0 .0 0 2 .1 l 1 21 2 2 1 . 3 3 l b 19 2 1 &8 j H IS l 0l 1 0 1 04 0 52 .1 l l4 7 r. ' - .1 1 - -0 9 1 ' 41 41 **2 0 10 T u u l IllbM TVtd num ber n( h rtM lI A n tic ip a i ! urn* b ir of b rttk i (on b u n of chrom o som e i n |i b | X' 1 : IH 7 (1 h i, 19 1 5 ,1 3 2 J.G 4 o.c, 0 . 5 3 | 2 . 5( .1 .0 9 N o . 10. i l . I d e c r m o f fr r * l M n . P > 005 - 71 . j 1 8 .7 b 0 .2 2 | :i.2 i : 1 ! 1 IPM | | lb.07 K .4 fi l (> .0 4 I 188 10 .2 1 0 . 2 0 0 . i d | 1 0 . i l 1 This Ijypothesis iriehloroa thlorine a irtected 1 of2,-D - ejtogenesi Tirlous er. The cytogenetic activity of 2,<4-D In mice was investigated in-doses of 300 mg/kg (LD^q )i 100 mg/kg (LD,-n/3), 50 50 mg/kg (LD5c0n/6 ), and 10 r.g/kg (LD5^0n/30). The data obtalni In chromosome analysis of bone-marrow cells from these mice are given In Table 3 whence It can be seen that exposure to the preparation in doses of 10 and 50 mg/kg, which did cause visible symptoms of Intoxication, produced an aberrant-cell frequency identical that In the control. The number of aberrant metaphases differed reliably from the spontaneous level after administration of 2,1<-D in doses of 100 and 300 mg/kg, which caused pronounced symptoms of Intoxication (P < 0.05, P < 0.001). The increase In aberration frequency was accompanied by a rise in the average number of abnormalities per subject and per aberrant metaphase, principally as a result of appearance of cells( with multiple aberrations (Fig. 2). Single acentric fragments predominated among the Induced abnormalities. Our investigations thus showed that the herbicide 2,^-0 is capable of damaging thg somatic-cell chromosomes of animals and man. However, a cytogenetic effect developed mouse bone-marrow cells only under the action of toxic doses of this preparation, so tjj 2,4-D can obviously be regarded as a weak mutagen for mice. The preparation induced chromosome aberrations In human lymphocytes exposed to concentrations that did and dld^ have a cytotoxic action. Cone (In lymph from unpe asltive 1 s ig n th ;Iteard. KFERENCE Human chromosomes in vitro are thus more sensitive *0 the injurious action of 2,1- than mouse bone-marrow cnromosorr.es in vivo. These out a again emphasize the importance of 2451 e In the number o f; e the dependence oo _-.ilan organism that this preparation is not metabolized, Is excreted unaltered, enters ^Tgonads, and can pass through the placental barrier [13.11*]. which probably accounts 2 "ts teratogenic effect [13-15]. i e r t h e a c t i o n 0f , d o m i n a t e d among on, symmetric t h i s 2 , it -D onorm allty spectru*ed a c e n tric fragm.,,^ r l b u t e d randomly 0r tily d i s t r i b u t e d oytr i r m s . The maximum id s h o r t arm s (70.5 * v<- i 5v. rPv r x )> ev ? Fig. 1. Symmetric chromatid exchange between chromosome A-l and C-group chromosome. 2,*t-D, In vitro, 0.002 ug/ml, magnification of 10 * 90. Fig. 2. Multiple aberrations, 2.H-D, In vivo, 300 mg/kg, magnification of 10 * 90. 3 This herbicide may be distributed in similar fashion In the human body. This ,,rjothesls is supported by data obtained with volunteers given the herbicide 2,^,5lehloroacetlc acid (2,4,5-T), a preparation differing from 2,**-D in having an extra citrine atom [15]. After a single oral administration of 2,*1,5-T, the herbicide was :::ected in the blood and was excreted unaltered In the urine for three days. If the fat-.'2,*l-D in the human body Is similar, this preparation presents a genetic r.aaard ,;j a .ogeneticaliy active compound, so chat it is necessary to prevent its uptake cy mar. from arisus environmental objects. Table 3 Frequency and Types of Chromosome A b e r r a t i o n s i n Mice Poisoned with Different Doses of 2,^-D ;s of 300 mg/leg The data obtain .n Table 3 wh ig/kg, which .ency Identical. .ly from the : m g / k g , which increase in ' abnorm alltle arance of cell ..tea among the ; of damaging Tect develope eparatlon, s o atIon Induced ( hat did and 6 2 ns 10 no 100 V Cw>* trai .* a \E e - *s 5e 2 e z 1! 1 reauencr a t ahetrtm m etaphases. % hfsM n v t ti celts w ith m ultiple tU m iw in in tftem tw iM f GS in O* m #% * ZJ l C *: t ih f r r ilM in i T r p e s o f nerraiMM p e t 1OO c r lta * i l! * ? 5 iti 3c e C a IE C e II2 ~ 2 6 1200 0 J .1 3 i0 .l6 5 0 0 4 0 .0 0 3 3 1.0 0 0 .2 5 0 0 .0 8 3 0 6 12 0 0 0 .8 3 .1 * 0 .2 6 4 0 . 0 8 1 0 .0 14 0 . 0 ( 1 7 1 .4 0 1 .0 0 0 0 . 0 8 3 0 .0 8 3 G 1200 1 .7 5 0 * 0 .3 7 8 0 .1 6 9 .5 25 0 .0 2 0 6 1 .1 9 1 .8 3 3 0 ,2 5 0 0 6 1200 3 .0 8 3 ^ 0 .4 9 9 1 .2 8 4 3 .3 114 0 .0 9 6 0 3 .0 0 8 .5 8 3 0 ,7 5 . 0 .1 6 7 0.700 0 010 1 0 0 0 o . n o o ^ 6 4 0 0 7 0 . 0 0 7 0 1 .0 0 Conclusions. The cytogenetic action of the herbicide 2,*J-D was Investigated In vlcr lymphocyte cultures from human peripheral blood) and In vivo (In bone-marrow cells 2 unpedlgreed white mice). It was shown that human chromosomes In cultures are more JJltive to the Injurious action of this preparation. The results obtained enable us to the herbicide 2,**-D to the class of substances presenting a potential genetic F ences s action of 2, the importane' J. Unrau, Can. Seed Growers Assoc. 1952-1953 Ann. Report., pp. 25-28, 1953J. Unrau, Can. Seed Growers Assoc. 1953-195** Ann. Report., pp. 37-39. 195**. Kallak and L. Yarvekylg, Acta blol. Acad. Scl Hung., vol. 22, pp. 67-73, 1971. Hakeem and A. S hehab, Abstr. Pap. I Egypt. Congr. Bot. Cairo, pp. 3**-35, 1972. N. Kulikov, A. A. Ezerzha, M. I. Ovchinnikova, and A. I. Mochalkln, Fizlologlya 2452 55* Urt : 6 . E. G. Berln and S. Yu. Buslovlch, 5th Congress of Hygienists, Epidemiologists 1] and Infectious-Disease Specialists of Belorussia, coll. 1 [in Russian], Minsk, pp. 78-70 il 1971- 7. L. Dlrvlng and M. Sunner, Heredltas,'vol. 63, pp. 115-122, 1971. _ 8 . A. E. Kulakov, collection: Application Hygiene and Toxicology of Pesticides au Symptomatology of Pesticide Poisoning [in Russian], Kiev, pp. 351-353, 1970. 9. S. Yu. Buslovich, Ya. E. Kenlgsberg, F. D. Koldobskaya, G. I. Moskovko, V. | Sklyadneva, I. V. Voinova, and M. G. Mll'chlna, collection: Application Hygiene and Toxicology of Pesticides and Symptomatology of Pesticide Poisoning [in Russian]-, Kiev, PP. 341-351, 1970. 10. M. A. Plllnskaya, Genetlka, vol. 6 , pp. 158-163 1970. 11. A. I. Kurinnyl, Author's Abstract of Candidate's Dissertation [in Russian], Ki,'I 1972. ' 12. N. A. Plokhlnskll, Biometry [in Russian], Izd. MGU, Moscow, pp. 143-145, 1970. 13. D. Clark, J. Yong, R. Younger, L. Hunt, and J. McLaran, J. Agrlc. Food. Chea., vol. 12, pp. 43-45, 1964. 14. A. Kurt-Erne, Acta vet. scand., vol. 7, pp. 240-256, 1966. 15. L. V. Martson, collection:- Application Hygiene and Toxicology of Pesticides tM.1 Symptomatology of Pesticide Poisoning [in Russian], Kiev, pp. 258-261, 1971. 1 16. A. Matsumura, Jap. J. Ind. Health, vol. 12, pp. 446-451, 1970. 21 June 1973 All-Union Scientific-Research Institute of the Hygiene and Toxicology of Pesticide, I Polymers, and Plastics of the Ministry of *] Public Health of the USSR, Kiev rJ 10 2 4 5 $ ' / / / O-^,6P V 2454 Am eucan J o u in a l o r E pidemiology Copyright 1982 by The Johns Hopkins University School of Hygiene and Public Health All rights reserved Vol. 115, No. 5 Printed, in V S A . NOTICE THIS MATERIAL MAY BE PROTECTED BY COPYRIGHT LAW TITLE 17 li.S . COOE LEUKEM IA AND FARM PRACTICES IN IOWA' LEO N F. BU RM EISTER, STEPH A N IE F. VAN H E R and PETER ISACSON Burmeister, L F. (Dept, of Preventive Medicine and Environmental Health, University of Iowa, Iowa City, iA 52242), S. F. Van Lier and P. isacso n . Leukemia and farm practices in Iowa. Am J Epidemiol 1982;115:720-8. Death certificate analyses of 1675 white, male lowans over age 30 years who died of leukemia in 1964-1978 were completed. Each case was matched to two controls on age (within two years) at death, county of usual residence and year of death. Consideration of usual occupation, as recorded on the death certificate, resulted in an odds ratio for leukemia mortality among farm ers of 1.24 (p < 0.05). The highest odds ratios for farmers were observed in those born after 1890, those dying after 1970, and those dying at age 65 years or younger. Odds ratios for farmers were also elevated in counties with high soybean and corn production per acre for those born between 1890 and 1900. For those born after 1900, odds ratios for farmers were increased in counties with the greatest numbers of egg-laying chickens and the largest number of acres treated with herbicides. The types of leukemia causing elevated mor talities in Iowa farmers were chronic lymphatic and unspecified lymphatic. Mortality from unspecified lymphatic leukemia was associated with com per acre, number of milk cows and number of egg-laying chickens. agricultural workers' d iseases; death certificates; leukemia; mortality During the past two decades, several studies (1 -6 ) have concluded that farm ers are subject to increased m ortality from leukem ia. The studies have been based on a wide range of geographic areas, including Great Britain (5), the en tire U nited States (1, 6) and the western United States (2 -4 ). Of particular con cern are the upper midwestern states be cause of the importance of farming in these states and because of the identifica tion of high-rate leukem ia m ortality counties in this area (6). More recent studies (7) have continued to indicate that leukemia mortality rates are elevated in the midwestern states. Al though mortality from all cancers was Received for publication A u g u st 31, 1981, and in final form N ovem ber 3, 1981. 1From th e Dept, of Preventive M edicine and E n vironm ental H ealth, U niversity of Iowa, Iowa C ity, IA 52242. (R eprint requests to Dr. B urm eister.) T his w ork w as supported by Public H ealth Service g ran t 1 R01-CA24302-01-EDC from the N ational C ancer Institute. lower in Iowa farmers, leukem ia was one of six cancers w ith statistically signifi cant elevated m ortality (8). A study of Nebraska death certificates by Blair and Thom as (9) also indicated an increased m ortality from leukem ia in farmers. The Nebraska study is extrem ely important since it attempts to identify farming prac tices associated with leukem ia. The fann ing practice in Nebraska most strongly associated with leukem ia mortality on a county basis is corn production. In contrast to the suggestion that fann ing practices peculiar to corn production m ay be associated w ith leukem ia, the possibility that dairy farming may be as sociated w ith leu kem ia has also been suggested (1 0 -1 6 ). Not all epidemiologic stu d ie s e v a lu a tin g th e association of dairy cattle and leukem ia have been posi tive, however (17, 18). Therefore, further research to identify suspected farming practices is necessary. Because of its high corn and dairy pro- 720 2455 . 0 - ^ LEUKEMIA IN IOWA FARMERS 721 duction, Iowa provides an excellent oppor tunity to compare the association of sus pected farming practices with leukemia. Iowa ranked first in corn production by state in 1950 and 1960, compared to fifth in 1950 and third in 1960 for Nebraska (19, 20). Although Iowa's dairy production (number of cows and heifers two years old and over kept for milk) did not rank as high nationally (fifth in both 1950 and in 1960) as did corn production, it is much higher than that of Nebraska (19th and 18th in 1950 and 1960, respectively). It may be that Nebraska's dairy production is not sufficiently large to allow any as sociation with leukem ia mortality to be detected; therefore, the Iowa death cer tificate study was completed to determine which farming practices are associated with leukemia mortality rates. Materials and methods The methods utilized in the Nebraska study were duplicated whenever possible to assure comparability of the two studies. The Nebraska study was based on deaths in 1 9 5 7 -1 9 7 4 , whereas the Iowa study was based on deaths 1 9 6 4 -1 9 7 8 . The fol lowing steps, however, are common to the two studies: 1) The records of all white males, aged 30 years or more at tim e of death from leukemia as classified by the Seventh (code 204) and E ighth (codes 2 0 4 -2 0 7 ) Revisions of the International Classifica tion of D isea ses (ICD) (21, 22), were abstracted from computer listings. 2) For each leukem ia death (1675 in Iowa compared to 1084 in Nebraska), two nonleukemic deaths were selected as con trols. The controls w ere m atched by county of usual residence, age at death ( two years) and calendar year of death. When more th an two elig ib le controls were identified for a case, the two controls included in the study were selected ran domly. Only w hite m ales were included in both studies. 3) The usual occupation indicated on the Iowa death certificate was coded ac cording to the 1960 Census (23) for the years 1 9 6 4 -1 9 7 0 and according to the U nited States Bureau of Labor (24) for 1971-1978. The entire Nebraska study was based on occupations defined by the Bureau of the Census. However, both studies combined all "non-farmer" occu pations. 4) Farm owners, tenants and laborers were all considered "farmers." Iowa counties were ranked according to 1949 crop and livestock production pro vided by the Iowa Crop and Livestock Re porting Service and by pesticide usage provided by the 1964 agricultural census (25), which is the only year for which pes ticide usage data are available. Crop and livestock production figures from 1949 were used to provide a 15-year lag period from tim e of production until the first year included in the death certificate analyses. However, agricultural produc tion in Iowa counties has changed very little during the past three decades. Spearman rank correlation coefficients for Iowa counties ordered for each of the major agricultural production figures in 1949 and 1974 were highly significant (p < 0.001). The geographic distributions of the highest producing 33 counties (of 99 coun ties) for selected commodities are indi cated in figure 1. Ratios of production of the median county in the highest produc ing 33 counties to the median county in the lowest producing 66 counties ranged from 1.52 for acres in oats to 3.49 for acres in soybeans. Estimated relative risks and associated confidence intervals were computed as suggested by M iettinen (26). All computa tions utilize the matching of two controls to each case. Results Heart disease, stroke and circulatory disease accounted for 43.5 per cent of the control deaths in Iowa (compared to 54.2 2456 722 BURMEISTER, VAN LIER AND ISACSON F igure 1. G e o g ra p h ic d is tr ib u tio n s o f h ig h e s t p ro d u c in g 33 Io w a c o u n tie s fo r s e le c te d a g ric u ltu ra l pro duction characteristics. A, m ilk cows; B, com ; C, soybeans; D, herbicides; E, egg-laying chickens. per cent in Nebraska). Cancer deaths other than leukemia totaled 18.9 per cent in Iowa (compared to 10.3 per cent in Nebraska). The distributions of usual occupation for both cases and controls are quite sim i lar in Iowa and Nebraska (table 1). Also similar are the elevated risks of leukemia m ortality for farmers. A n odds ratio of 1.25 (95 per cent confidence lim its of 1.05 and 1.49) was computed for N ebraska. The odds ratio for farming in Iowa was 1.24 w ith 95 per cent confidence limits of 1.09 and 1.42. Table 2 summarizes the odds ratios for leukem ia m ortality computed for sepa rate strata according to year of birth, year of death and age a t death. Iowa farmers born after 1890 and those whose age at death was less than or equal to 65 years have odds ratios sig n ific a n tly greater than 1. These results are sim ilar to those found in Nebraska where farmers born idler 1900 and those aged 65 years or less 2457 LEUKEMIA IN IOWA FARMERS 723 Tabu 1 Distributions of usual occupation, by death certificate analysis, o f leukemia deaths and matched controls, white males over 30 years o f age, resident in Nebraska dying 1957-1974, and resident in Iowa dying 1964 --1978 Occupational group T each ers E ngineers, scientists F a n n e rs Clerks, salespersons C arpenters, woodworkers P rin te rs M achinists, m echanics Laborers No occupation listed O ther T o ta l Iowa No. Cases Nebraska % No. % 17 1.0 49 2.9 661 39.5 116 6.9 89 5.3 12 0.7 71 4.2 116 6.9 5 0.3 539 32.2 9 0.8 25 2.3 433 39.9 84 7.7 31 2.9 3 0.3 33 3.0 49 4.5 65 6.0 352 32.5 1675 1084 Controls Iowa Nebraska No. % No. % 37 64 1184 230 183 8 162 298 19 1165 1.1 1.9 35.3 6.9 5.5 0.2 4.8 8.9 0.6 34.8 12 0.6 66 3.0 781 36.0 163 7.5 52 2.4 9 0.4 77 3.6 126 5.8 161 7.4 721 33.3 3350 2168 Ta b u 2 Odds ratios for leukemia mortality in white, male Iowa farmers over 30 years of age, according to year of birth, year of death and age at death, 1964-1978 Stratum Year of birth 1869-1889 1890-1900 1901-1947 Year of death 1964-1970 1971-1978 Age (years) at death <65 *66 Cases No. of farmers % Farmers 166 49.7 290 47.2 205 28.2 344 40.4 317 38.5 Controls No. of farmers % Farmen 392 52.0 488 39.9 304 22.2 640 37.6 544 33.0 Odds ratio 0.89 1.36 1.39 1.15 1.36 95% CL* 0.67-1.18 1.10-1.68 1.11-1.73 0.96-1.39 1.11-1.66 116 24.1 166 18.5 1.36 1.02-1.80 545 45.7 1018 41.5 1.21 1.04-1.41 * CL. confidence limits. at death had increased odds ratios. The odds ratio for farming was also elevated for those dying after age 65 years in Iowa, whereas it was not elevated in Nebraska. The odds ratio for years of death in 1 971-1978 was elevated in Iowa; how ever, the odds ratio for the years of death 1957-1965 was markedly higher in Ne braska. As noted in table 2, the greatest risk for leukemia mortality in Iowa farmers ap pears to be in those born after 1890. Therefore, analyses stratified by counties according to selected county production figures were completed by year of birth of the cases. The results are summarized in table 3. As might be expected from the low odds ratio for Iowa farmers in those born before 1890 (table 2), there are no significantly elevated risks in this cohort. Soybeans per acre and corn per acre are associated with increased leukem ia m ortality risks among farmers for those born from 1890 to 1900. However, neither association is sta tistic a lly sign ifican t for those born after 1900. The relatively low livestock producing counties have increased odds V K> OT CO VT\ 6s T able 3 Odds ratios for leukemia mortality in white, male Iowa farmers over 30 years o f age, according to selected county crop and livestock production, 1964-1978 Production categories by counties S o y b e n n s/a cre 33 highest O thers C orn/acre 33 highest O thers M ilk products sold 33 highest O thers C attle 33 highest O thers Hogs 33 highest O thers M ilk cows 33 highest O thers Egg-laying chickens 33 highest O thers F ertilizer 33 highest O thers Insecticides 33 highest O thers H erbicides 33 highest O thers * CL, confidence limita. Before 1890 Odds ratio 95 * CL* 0.672 1.032 0.831 0.947 0.906 0.877 0.969 0.831 0 782 0.987 0.954 0.841 1.105 0.792 1.260 0.730 0.731 0.954 0.767 0.951 0 .4 1 5 -1 .0 8 8 0 .7 2 7 -1 .4 6 5 0 .5 5 4 -1 .2 4 7 0 .6 3 8 -1 .4 0 6 0 .5 8 6 -1 .4 0 1 0 .6 0 5 -1 .2 7 1 0 .6 3 2 -1 .4 8 5 0 .5 7 0 -1 .2 1 3 0 .5 1 2 -1 .1 9 3 0 .6 7 5 -1 .4 4 6 0 .6 2 3 -1 .4 6 1 0 .5 7 6 -1 .2 2 8 0 .6 8 3 -1 .7 8 8 0 .5 5 7 -1 .1 2 5 0 .7 8 6 -2 .0 1 8 0 .5 1 2 -1 .0 4 2 0 .4 2 0 -1 .2 7 1 0 .6 8 6 -1 .3 2 7 0 .4 6 2 -1 .2 7 3 0 .6 7 6 - 1.337 Year of birth (of case) 1890- 1900 Odds ratio 95% CL 1.594 1.233 1.634 1.201 1.187 1.474 1.287 1.414 1.246 1.429 1.171 1.490 0.954 1.627 1.089 1.548 1.323 1.381 1.104 1.528 1 .1 2 9 -2 .2 5 0 0 .9 4 0 -1 .6 1 6 1 .1 6 8 -2 .2 8 5 0 .9 1 2 -1 .5 8 2 0 .8 3 5 -1 .6 8 5 1 .1 2 6 -1 .9 2 9 0 .9 2 1 -1 .7 9 8 1 .0 7 2 -1 .8 6 4 0 .8 7 3 -1 .7 7 8 1 .0 9 5 -1 .8 6 5 0 .8 2 7 -1 .6 5 8 1 .1 3 6 -1 .9 5 3 0 .6 5 9 -1 .3 8 0 1 .2 5 0 -2 .1 1 8 0 .7 6 7 -1 .5 4 8 1 .1 8 3 -2 .0 2 6 0 .9 2 2 -1 .9 0 0 1 .0 6 1 -1 .7 9 7 0 .7 7 3 -1 .6 7 5 1 .1 7 1 -1 .9 9 4 A lter 1900 Odds ratio 96% CL 1.405 1.376 1.384 1.389 1.302 1.454 1.231 1.522 1.400 1.376 1.446 1.345 1.532 1.314 1.340 1.414 1.129 1.626 1.595 1.278 0 .9 7 9 -2 .0 1 6 1 .0 3 8 -1 .8 2 4 0 .9 8 0 -1 .9 5 4 1 .0 3 9 -1 .8 6 7 0 .9 2 6 -1 .8 2 9 1 .0 8 4 -1 .9 5 0 0 .8 7 9 -1 .7 2 2 1 .1 3 1 -2 .0 4 9 1 .0 0 8 -1 .9 4 9 . 1.019-1.857 1 .0 2 7 -2 .0 3 6 1 .0 0 4 -1 .8 0 2 1 .0 5 3 -2 .2 2 9 0 .9 9 7 -1 .7 3 2 0 .9 2 9 -1 .9 3 4 1 .0 7 0 -1 .8 7 0 0 .7 6 2 -1 .8 7 3 1 .1 6 6 -1 .9 9 8 1 .1 0 5 -2 .3 0 1 0 .9 6 6 -1 .6 9 1 LEUKEMIA IN IOWA FARMERS 725 ratios. None of the agricultural production figures evaluated in Nebraska led to increased risk am ong farmers in the 1890--1900 cohort. It is for those born after 1900 that the Iowa and Nebraska studies have the greatest inconsistencies. The odds ratios for farm ers in N ebraska were sig n ificantly greater than 1 in those counties with the highest production of com, cattle and hogs and highest number of acres treated with insecticides. None of these farming practices were associated with leukemia mortality in Iowa. Only acres treated with herbicides and egg-laying chickens per county were statistically significant at the 5 per cent level. The odds ratios for Iowa farmers for specific leukemia cell types are summarized in table 4. Only those dying in 1 9 6 8 -1978 are included in table 4 since the ICD Seventh Revision (used prior to 1968) may not separate acute lymphatic and acute m yeloid leukem ias. Both chronic lymphatic and unspecified lymphatic leukemias cause increased mortality in Iowa farmers. The odds ratios for chronic lymphatic leukemia are elevated in those born after 1890 (table 5). Although the odds ratios for unspecified lymphatic leukem ia are greater than 1 for each birth cohort, none is statistically significant, due in part to small numbers in each cohort. Odds ratios for chronic and unspecified leu kem ias according to county agricultural production Figures associated with combined leukemia types are summarized in table 6. Chronic lymphatic leukemia is elevated in both the high and low producing counties for the five county characteristics investigated. The strongest associations, both in magnitude of the odds ratios and differences in the high and low producing counties, are with soybeans per acre and acres treated with herbicides. Unspecified lymphatic leukemia mortality in farmers is associated with com per Table 4 Odds ratios for leukemia mortality in white, male Iowa farmers over 30 years o f age for specific leukemia types, 1 9 6 8 -1 9 7 8 Leukemia type A cute lym phatic C h ro n ic lym phatic U nspecified lym phatic A cute m yeloid C h ro n ic m yeloid U nspecified m yeloid -- C hronic m yeloid Leukem ia u n sp e c ifie d ICD No. 204.0 204.1 204.9 205.0 205.1 205.9 206.0 207.9 Cases No. of farm ers % Farm ers Controls No. of farm ers % Farm ers Odds ratio 95% CL* 28 28.9 69 35.6 0.68 0 .3 7 -1 .2 3 132 45.8 207 35.9 1.70 1 .2 2 -2 .3 8 64 51.2 102 40.8 1.66 1 .0 3 -2 .6 8 86 30.7 168 30.0 1.04 0 .7 4 -1 .4 8 46 32.6 90 31.9 1.04 0 .6 5 -1 .6 5 36 36.7 80 40.8 0.80 0 .4 5 -1 .4 1 10 32.3 19 30.1 1.07 0 .4 4 -2 .5 9 31 41.3 60 40.0 1.07 0 .5 8 -1 .9 7 * CL, confidence lim its. 726 BURMEIOTER, VAN LIER AND ISACSON Table 5 Odds ratios (ORs) for leukemia mortality in white, male Iowa farmers over 30 years of age for selected leukemia types and year of birth, 1968-1978 type C h ro n ic lym phatic U nspecified lym phatic ICD No. 204.1 204.9 Before 1890 OR 9 5 * CL* 1.00 1.58 0 .5 4 -1 .8 5 0 .6 5 -4 .5 4 Year of birth 1890-1900 OR 95* CL 2.03 2.30 1 .2 4 -3 .1 0 0 .9 7 -6 .9 7 After 1900 OR 95* CL 1.80 1.25 1.09-2.97 0 .6 4 -2 .5 5 * CL, confidence lim its. Table 6 Odds ratios (ORs) for leukemia mortality in white, male Iowa farmers over 30 years o f age, according to selected leukemia types and selected county crop and livestock production, 1968 -1978 County characteristics Soybeans/acre C o rn /acre M ilk cows E gg-laying c h ic k e n s H erbicides C hronic.lym phatic U nspecified lym phatic C hronic lym phatic U nspecified lym phatic Chronic lym phatic U nspecified lym phatic C hronic lym phatic U nspecified lym phatic C hronic lym phatic U nspecified lym phatic Highest 33 counties OR 95* CL* 2.21 0.62 1 .3 3 - 3.66 0 .2 5 - 1.52 1.34 4.63 0 .8 7 - 2.06 1 .8 2 -1 1 .7 4 1.19 4.94 0 .7 6 - 1.85 1 .9 6 -1 2 .4 7 1.36 2.47 0 .8 2 - 2.25 1 .0 3 - 5.92 1.89 1.21 1 .1 6 - 3.08 0 .5 1 - 2.85 O ther counties OR 95* CL 1.39 2.49 0.97-2.00 1.38-4.48 1.94 1.29-2.92 1.00 . 0.56-1.80 . 2.10 0.94 1.41-3.14 0.52-1.70 1.80 1.37 1.25-2.59 0.77-2.45 1.50 1.90 1.03-2.18 1.07-3.37 * CL, confidence lim ite. acre, number of milk cows and egg-laying chickens. D is c u s s io n Mortality from several types of cancer has been shown to be elevated in farmers (2, 8). These include stomach, prostate and lip cancer, as well as lymphomas and multiple myeloma. However, leukemia is perhaps the cancer most consistently as sociated with farming during the past 30 years (1 -9 ). Therefore, it is incumbent upon epidem iologists not m erely to re peatedly demonstrate that such an as sociation exists, but to diligen tly search for reasons for the association. The Nebraska study of B lair and Thomas (9) represents an attem pt to iden tify such reasons or farm ing practices. Previous epidemiologic evidence has as sociated dairy farm ing w ith leukemia m ortality in farmers (1 0 -1 6 ). The Ne braska study is particularly important since it implicates corn production with leukem ia in those born after 1900, rather than any measure of dairy production. The results of the Iowa study lend some support to those found in Nebraska. The odds ratios for farmers based on the high producing counties are statistically sig nificant for only corn and soybean produc tion for those born from 1890 to 1900. Ap parently, soybean production in Nebraska is not sufficient to be evaluated for associ ation with leukem ia m ortality in farmers; however, the association o f corn produc tion w ith leu k em ia m o rta lity in both states indicates th a t modern farming 26 LEUKEMIA IN IOWA FARMERS 727 practices used in corn production may be a cause of the higher leukemia mortality rates in farmers. This possibility is given credence by the fact that corn production is implicated only in those born idler 1890 in Iowa and after 1900 in Nebraska. In addition, the number of acres treated with herbicides in Iowa and the number of acres treated with insecticides in N e braska are associated w ith leukem ia mor tality in farmers born after 1900. These results also tend to im plicate modern farming practices as possible causes of leukemia. There is no evidence linking leukemia mortality in farmers with corn production, use of herbicides or use of in secticides in either state for those bom be fore 1890. The fact that the number of egg-laying chickens is associated with increased leukemia mortality in farmers was not anticipated from the results of the N e braska study. However, M ilham's study (4) of Washington and Oregon death cer tificate data did indicate that a sta tis tically significant association existed be tween farming and leukem ia mortality, and that the greatest excess of leukemia mortality was in poultry farmers. Analyses by type of leukemia indicate that chronic and unspecified lymphatic leukemias cause increased mortalities in Iowa farmers. Thus, it appears that it is the lym phatic leukem ias that are of greatest concern. Sixty-three per cent of incident acute lym phatic leukem ias in Iowa males in 1 9 6 9 -1 9 7 9 occurred in in dividuals under age 30 years. Con sequently, relatively few (table 4) acute lymphatic deaths in those over age 30 years were included in this study. Analyses by leukem ia type are also of importance because of strong associations of unspecified lymphatic leukem ia with number of dairy cows and corn production per acre by county. Donham et al. (14) showed significant association between acute lymphatic leukem ia incidence in Iowa and dairy farming. As noted above, acute lym phatic leukem ia m ortalities were of lim ited number in this study; however, it is of importance to note the continued evidence of association between dairy farming and lymphatic leukemia. Since corn per acre was also highly as sociated with unspecified lym phatic leukemia mortality, any elem ents com mon to both com and dairy production are worthy of further investigation. Many agricultural innovations that have greatly increased com production, such as extensive use of hybrids and pes ticides, have been introduced since World War II. One that is particularly important is commercial fertilizer usage, increased from 8,425,000 tons in the United States in 1930 to 18,400,000 tons in 1950 (27). The amount of nitrogenous fertilizer applied has added to the agricultural runoff problem (28). T his problem is exacerbated by the fact that the nitroge nous waste of dairy anim als is much greater than that of other common farm livestock (28). Although highly specula tive, one mechanism of increasing the risks for farmers for leukemia and other cancers is contamination of shallow farm wells and farm ponds. This research, of course, offers no direct evidence that shal low wells m ight contribute to increased farmer m ortality from leukem ia. How ever, studies such as this and that of Blair and Thomas (9) are important since they go beyond identification of farming as a risk function and attem pt to identify farm ing practices and specific m echa nisms that must be closely studied if the cancer risks of farmers are to be de creased. References 1. G u ra ln ic k L. M o rta lity by occupation an d cau se of d eath . V ital S ta tistic s S pecial R eport 1963:53(3). 2. M ilham S. O ccupational m ortality in W ash ington sta te , 1950-71. Vol. 1-3. D H EW <PHS). W ashington, DC: US GPO, 1976. 3. Fasal E, Jackson EW , K lauber MR. Leukem ia and lym phom a m ortality and farm residence. Am J E pidem iol 1968;87:267-74. 728 BURMEISTER, VAN HER AND ISACSON 4. M ilham S Jr. L eukem ia an d m ultiple m yelom a in farm ers. Am J E pidem iol 1971;94:307-10. 5. A delstein AM. O ccupational m ortality: cancer. A nn Occup H yg 1972;15:53-7. 6. M ason T J, M cKay FW , Hoover R, e t al. A tlas of can cer m o rta lity in U S counties: 1950-69. D H EW p u b licatio n no. (NTH) 75-760. W ash ington, DC: US GPO, 1975. 7. Linos A, K yle RE, E lveback LR, e t al. L eukem ia in O lm stead C ounty, M innesota 1965-1974. M ayo C lin Proc 1978;53:714-18.- 8. B urm eister LF. C ancer m ortality in Iowa farm ers, 1971-1978. JN C I 1981;66:461-4. 9. B lair A, T hom as TL. L eukem ia am ong N e braska farm ers: a death certificate study. Am J Epidem iol 1979;110:264-73. 10. K hokhlova M P, R ak h m am in PP. C om parative study on geographical distribution of hum an cattle leukosis. In: C om parative leukem ia re search, 1969. B ibl H aem ato l 1970;36:654-8. 11. H enricson B, R in g ertz N . C o m p arativ e stu d ies on th e geographical distribution of hum an and bovine leukem ia. In: C om parative leukem ia re search, 1967. B ibl H aem atol 1968;31:331-52. 12. H eath CW, Jr. H um an leukem ia, genetic and en v iro n m en tal c lu ste rs. In: C om parative leu k em ia re se a rc h , 1969. B ibl H aem ato l 1970;36:649-53. 13. Lem on HM , T w iehaus M J, W ilson RB, e t al. Sym biotic hum an and bovine lym phom a. Proc Am Assoc C ancer R es 1966;7:41. 14. D onham K J, B erg JW , S aw in RS. Epidem iologic relatio n sh ip s of the- bovine pop u latio n and h u m an leu k em ia in Iow a. A m J E pidem iol 1980;112:80-92. 15. W isinew ski D, W einreich J . L ym phatische leu k em ie bei v a te r un d sohn. B lu t 1966;12: 241-4. 16. B artsch DC, S p rin g er F, F u lk H. A cute nonlym phocytic leukem ia, an a d u lt cluster. JA M A 1975;232:1333-6. 17. K varnfors E, H enricson B, H ugosan G. A sta tis tic a l s tu d y on f a rm a n d v illa g e lev e l on th e pos sible rela tio n s betw een h u m an leukem ia and bovine leu k o sis. A cta V et S can d 1975:16:163-9. 18. P re is te r W A, O lein ick A, C o n n er GH. Bovine le u k o s is a n d h u m a n c a n c e r. L a n c e t 1970;1: 367-8. 19. U n ited S ta te s D e p artm en t o f A g riculture. Ag ric u ltu ra l S ta tistic s 1950. W ash in g to n , DC: US GPO, 1950. 20. U n ite d S ta te s D e p a rtm e n t o f A g ric u ltu re. Ag r i c u l t u r a l S ta tis tic s 1960. W a s h in g to n , DC: US GPO, 1960. 21. W orld H e a lth O rg an izatio n . M anual of the In te rn a tio n a l S ta tis tic a l C la ssific a tio n of Dis eases, In ju rie s, a n d C au ses o f D eath , 7th Revi sion. G eneva: W HO, 1955. 22. W orld H e a lth O rg an izatio n . M an u al of the In te r n a tio n a l S ta tis tic a l C la ssific a tio n of Dis eases, In ju ries a n d C au ses o f D eath , 8th Revi sion. G eneva: W HO, 1967. 23. U nited S tates B u reau of th e C ensus. 1960 Cen su s o f P opulation C lassified Index of Occupa tio n s a n d In d u stries. W ash in g to n , DC: US GPO, 1960. 24. U n ited S ta te s D e p artm en t of L abor. Dictionary o f O c c u p a tio n a l T itle s , 3 rd e d . W a s h in g to n , DC: U S GPO, 1965. 25. U n ited S tates B ureau of th e Census. 1964 Cen su s o f A g ric u ltu re . V ol. I. A rea R eports. W ashington, DC: US GPO, 1966. 26. M ie ttin e n OS. E stim a tio n o f re la tiv e risk from in d iv id u a lly m a tc h e d se rie s . B iom etrics 1970;26:75-86. 27. U n ited S tates D ep artm en t of A griculture. Ag r i c u l t u r a l S ta ti s t i c s 1951. W a s h in g to n , DC: US GPO, 1951. 28. P an el on N itra te s of th e C oordinating Commit tee for S cien tific a n d T ech n ical A ssessm ents of E n v iro n m e n ta l P o llu ta n ts. N itrates: an envi ronm ental assessm ent. W ashington, DC: Na tional A cadem y of Sciences, 1978. 2463 , $-?d)o-35W> 5 2 4 6 4 .3l5 (A 5 r T c icology Letters. 29 (1985) 13 7 -1 4 4 gK vter 137 Frasseuo, I he synthesis of \b u s e , 3 (1982]j \ holate secretor 83) 86A. i '-> f hep atic Na, K.ced cholestasis^ (1984) UO-isi'J'' transsulfuraiio :m ,, 259 (1984^' P- B ain. R.k. r. path w ay in cir- and irreversible- TOXLetl. 1508 DNA AND PROTEIN SYNTHESIS INHIBITION IN CHINESE HAMSTER OVARY CELLS BY DICHLOROPHENOXYACETIC ACID (Dichlorophenoxyacetic acid; cell cycle; DNA synthesis; protein synthesis) VIVIANA A. R IV A R O LA . JO R G E R. BERGESSE and H C TO R F. BALEGNO* Departamento de Biologa Molecular, Universidad Nacional de Rio Cuarto. 5800 - Rio Cuarto. Crdoba (Argentina) (Received Septem ber 9 th . 1985) (Accepted O ctober 10th. 1985) * * thyl-PG Et p . Hepatology, gN d R. Tritapepe?-* a t i bile it?i ie. R elationshi nvesi. (Suppl. lls, P h arm aco lJ i S-adenosyi-i-'jJ E ur. J. Drug- SUMMARY T he effects o f th e h erb icid e d ich lo ro p h en o x y a c etic a d d (2,4-D ) o n D N A a n d p ro tein synthesis were investigated in Chinese ham ster ovary cells (C H O ) em ploying tw o differen t m ethods. The results showed that the herbidde affects D N A and protein synthesis depending on the stage of grow th and m ethod of treatm en t. 2,4-D actio n a p p e a rs to c o n c e n tra te th e cells m ainly in th e G (/ S b o u n d a ry o f the cell cycle. The effect is expressed as a n in h ib ito n o f D N A a n d p r o td n sy n th esis. T his effect w as revealed n ot only by th e chem ical d e te rm in a tio n o f D N A a n d protein synthesis b u t also by ex p erim en ts using a u 'o ra d io g ra p h y , using th e labelling index to d etect th e in c o rp o ra tio n o f [3H ]th y m id in e in to the cells. Laoelling o f the cell n u d e u s was reduced m arkedly when cells treated with 2,4-D were in confluency for 4 days a fter reaching plateau g ro w th . ion in therapy, aphthylisothio- stradiol-ireated and L. Okoiic.SAM e) in rats. IN T R O D U C T IO N The herbicides 2,4-D and 2,4,5-Trichlorophenoxyacetic acid (2,4,5-T) are used ex tensively in modern agriculture. These compounds may be contaminants o f food d -stined for human consumption. An investigation seemed in order to elucidate cer tain mechanisms o f action displayed by these compounds. Previous investigations have demonstrated that the organochloride 2,4-D is capable o f exerting a detrimen tal effect upon fertilised chicken eggs painted with a 2,4-D solution [1]. The eggs tt *To whom correspondence should be addressed A bbreviations: C H O . Chinese h am ster ovary cells: 2,4-D , dichlorophenoxyacetic acid; 2 .4 .5-T. tnchlorophenoxyacetic acid. 2465 138 showed changes in hatchabiiity and the chicks were born with physical detects. * has also been reported [2] that 2,4-D produces alterations in cultured lym phocytes^|n with an increase in the rate o f sister chromatid exchange and clastogenicity. 2,4-D t and 2,4,5-T are also inducers o f meiotic abnormalities in wheat and other relati species [3]. 2,4,5-T inhibited the incorporation o f [`*C]thymidine and [JH]urid into the soluble pool o f L-929 cells and interfered with [JH]leucine incorporation^ into the proteins. These phenomena were accompanied by a cessation o f growth (4). The results of these investigations prompted us to study the effects of 2,4-D < the cell cycle o f hamster ovary cells (CHO) and to determine the biosynthesis DNA and proteins. MATERIAL AND METHODS A CHO strain (acquired from Dr. Petra Martinez o f the Fundacion de Genetic Humana, Buenos Aires, Argentina), kept in liquid nitrogen, was used for the it vestigations. The cells were grown as a monolayer using McCoy's culture rnedit: [5] supplemented with 15% bovine fetal serum and 50 /ig/m l gentamicin. Pla flasks with a 25-cmJ surface were used for the experiments. Trypsin (1:250 Difc 0.25% in Hepes buffer, pH 7.2 (6) was used to release the cells from the flasks, cells were treated for 16 h with hydroxyurea (HU; Sigma) at a final concentratiq o f 1.2 tnM in the culture medium from the moment the cells reached logarit growth, with a population o f approx. 2 x I0` cells per flask. The effect o f the 1 bicide on cells concentrated at some point from the Gi phase [7] was also studiS by maintaining the cells for 4 additional days in the same culture medium afti reaching confluency. All experiments were carried out in two series o f flasks: oa with the herbicide-treated cells and the other with the control cells in normal cultu medium. This investigation was also carried out to determine where in the cell i the herbicide was exerting its effects and to measure the recovery capacity of i treated with 1 mM 2,4-D for 24 h and subsequently changed to a normal mediu To determine recovery, the biosynthesis o f DNA and protein and cell division we followed for 16 h. As a final experiment, cells that were in confluency for 4 days were subjected i autoradiography, using [3H]thymidine as label [8]. The labelling index was dete mined for both treated and untreated cells. :> The synthesis o f DNA and protein was determined in all cases after giving a pulse with a mixture o f 1 jiCi/ml o f [methyi-i H)thymidine (Amersham, U.K. 5? Ci/mmol) and 0.16 pCi/ml o f L-[U-MClIeucine (Amersham, U.K. 10 mCi/mmol>.1 The radioactive thymidine was brought to 5 /M final concentration with cold' thymidine, and the cells were incubated at 37C. DNA and protein extraction from the-cells-after'the pulse with the radioactive compounds was performed as follows:^ the culture medium was withdrawn from the flasks and the monolayer rinsed once with PBS solution A [9J. The cells were trypsinised, and released after 5 min by ^ j RESUL Fig. (HU) 2466 il defects. 2 /mphocytes^ ricity. 2,4-D^ >ther relatq (3H]uridixj5 corporation! growth [4], of 2,4-D i synthesis of 139 gentle shaking immediately after which 3 ml medium containing 15Vo serum was added to prevent clumping. The cells were centrifuged at 1000 rev./min for 2 min, the supernatant was discarded and the pellet was resuspended in 10 ml saline solu tion. The ceils were then counted and centrifuged. DNA and proteins were isolated by the method o f Munro and Fleck [10]. The DNA solution was finally obtained jn a total volume of 2 ml of 0.2 M HCIO*, and the proteins in l ml of 0.5 N NaOH. The DNA concentration was determined by measuring the absorbance at 260 nm in a Beckman spectrophotometer, and proteins content by the method o f Lowry et al [II]. Radioactivity was determined in 0.2 ml o f DNA or protein solutions, with 2.5 ml o f a mixture composed o f toiuene/Triton X -100 (2:1) containing 0.02 g Vo of l,4-bis-2-(5-phenyl-oxazolyl)-benzene; phenyi-oxazolyi phenyl-oxazoiyl phenyl (POPOP) (Sigma) and 0.4 g Vo o f 2,5-diphenyloxazole (PPO, Amersham/Searle). A Beckman liquid scintillation counter was used. * RESULTS a n d d is c u s s io n Fig. 1 shows DNA synthesis in cells pretreated for 16 h with 1.2 mM hydroxyurea (HU) before transfer to a normal medium with or without 1 mM 2,4-D. The max- ubjected' was dete :iving a 1-J n, U.K. 5tf Ci/mmol)^ with cold ' iction from as follows^ rinsed once r 5 min by' fig . 1. T h e cells in lo g arith m ic grow th w ere tre a te d fo r 16 h w ith 1.2 m M H U b e fo re the cu ltu re m edium was changed for fresh m edium w ith or w ithout I mM 2,4-D . T he D N A -specific radioactivity a s deter mined. a . W ith 2.4-D ; , w ithout 2.4-D . 2467 <0 -3.5(0 "l Fig. 3. Cells grow ing in norm al culture m edium were kept fo r 4 a d d itio n al days at 37C a fte r reaching, plateau g rpw th-T he'm edium was then changed for fresh m edium w ith o r w ithout 2,4-D and the th esis o f D N A follow ed d u rin g 16 h. a . W ith 2.4-D , , w ith o u t 2.4-D . m 2468 D-afbS f r jtium synthesis was at 8 h in normal medium. 2,4-D produced a marked inhibition, which was almost total at 8 h. Protein synthesis (Fig. 2) peaked at 6 h in the control, while the 2,4-D-treated cells displayed a maximum at 4 h followed by a rapid fall to a minimum at 10 h. There was no change in the number of cells when the medium contained 2,4-D, but without the herbicide, cell division invariably occurred at 10 h. Fig. 3 shows the DNA specific radioactivity from 1-16 h in cells concentrated at some point of phase Gi after 4 days' growth following confluency, and transferred to normal medium with or without 2,4-D. In normal medium there was a delay in the synthesis of DNA, which reached its maximum value at 12 h. This would suggest that the ceils were in the initial stage o f G | when the medium was changed. When the medium contained 1 mM 2,4-D, this response was virtually absent throughout the 16 h o f the experiment. To verify that cells maintained in confluency for 4 days were capable of initiating DNA synthesis when treated with 2,4-D, an experiment was performed using autoradiography, and the labelling index was determined. The results are shown in Fig 4. The cells displayed diminished capacity for the incorpora tion o f [JH]thymidine in the presence o f 2,4-D, in comparison to those without the herbicide. On the other hand, protein synthesis in cells maintained at confluency showed a rapid increase (Fig. 3) almost equal to the control, when the new medium contained 2,4-D, although it decreased after 16 h incubation. In order to establish where the herbicide was acting in the cell cycle, a culture in logarithmic growth was Fig. 4. Cells were incubated for 4 days a fter reaching plateau grow th. T he m edium w as changed for another with or w ithout I mM 2 .4 -0 . and a 10-min pulse was given with I pC i/m l o f []H ]thym idinc every 2 h. A u to rad io g rap h y was carried o u t im m ediately. P ercentage o f labelled cells 12 h a fte r changing the culture m edium : open bars, control; solid bars, cells with 2.4-D. ^ 2469 <7P-/'=Zj> 142 r& Fig. 5. Protein-specific radioactivity o f ceils treated as indicated in Fig. 3. A. W ith 2,4-D ; , < 2 ,4 -D . exposed to the herbicide for 24 h. As can be seen in Fig.6, DNA synthesis wasji itiated when the ceils were treated with 2,4-D but decreased gradually, reachir minimum at 24 h (the cells did not multiply during this time). When the origin medium was removed, the cells rinsed and normal medium added, a rapid respoi in DNA synthesis was observed, reaching a maximum at 4 h (Fig. 6). This sugge that the cells were at the G |/S phase. The cells divided 16 h after normal me was added. Protein synthesis was also inhibited in cells treated with 2,4-D. Remov of the pesticide was followed by an increase in synthesis. The above results showed that the herbicide 2,4-D affects DNA synthesis, that this effect is expressed differently if the cells are treated with HU (Fig. 1) < are concentrated at an early stage o f Gi after confluency (Fig.3). In the latter case,1 it is not certain at precisely which point of phase Gi the cells are concentrated when! maintained in the original medium after attaining a growth plateau. According toj some investigators, the transformed cells accumulate in early Gi [12]; others are ofJ the opinion that the normal cells accumulate in early Gi and the transformed cells in lateGi [13]. The results presented in this investigation indicate that 2,4-D produc ed a cell concentration mainly in the G i/S phase of the cell cycle, resulting in retard ed cell growth. The peak in DNA synthesis 8 h after HU was eliminated from the' culture medium (Fig. 1) shows cell division at 10 h. The inclusion o f 2,4-D in the medium for 24 h and its subsequent removal produced a peak of DNA synthesis at ACKN< We manu tion \ nicas REFE' 1 R. egf 2 C. ch 2470 O- 3.5M 14} synthesis wasj aally, reaching hen the orig a rapid n). This sugge normal me 2,4-D. Remov i. synthesis, HU (Fig. 1) n the latter case? ncentrated wheni iu. According toj 2); others are ofj ransformed ceils* at 2,4-D producsulting in retardlinated from the i o f 2,4-D in the )N A synthesis at Fig. 6. 2,4-D to a final concentration of I m M , was ad d ed to a cell culture in logarithm ic grow th and DNA synthesis follow ed fo r 24 h. In oth er series o f flasks the m edium w ith 2.4-D w as rem oved after 24 h a n d replaced by a n o rm al cu ltu re m edium a n d the D N A synthesis follow ed fo r 24 h. a . W ith 2.4-D; , recovery with norm al medium. 4 h (Fig. 6), with cell division at 16 h. These observations may indicate that there was an elongation of the S or G: phase, or both, but the in vitro mechanisms of action o f 2,4-D are little understood at present. Definite conclusions at this point would be premature due to the many factors involved in the ceil cycle. ACKNOW LEDGEM ENTS We are grateful to Mrs. Donna E.M. de Balegno for her help in preparing the manuscript and to Mr. Adalberto Allione for his technical assistance. This investiga tion was supported by the Consejo Nacional de Investigaciones Cientficas y Tc nicas (Argentina). REFERENCES 1 R. D u ffard . G .M de M oro and A .M .E . D u ffard. H atching a n d lipid com position of chick brain from eggs treated with 2,4-D ichlorophenoxyacetic butyl ester. Toxicology, 24 (1982) 305. 2 C. K orte and S.M . Jalal, 2.4-D induced clastogenicity and elevated rates o f sister chrom atid ex changes in cullcred hum an lym phocytes. H eredity. 73 (1982) 224. 2471 Toxicology L Hscvier 3 R. NahU A l-N ajjar and A .S. Solim an. Cytological effecu o f herbicides, i. Effects o f 2,4-Dfc 2,4,5-T on m eiotic cells o f wheat and tw o related species. C ytology, 47 (19S2) 33. 4 L. D ra g sn e sa n d K. H elgetand. E ffects o f 2 ,4 ,5-T on the in c o rp o ra tio n o f [>4C ]thym idine, ['H]u an d L-(JH ]le u d n e in to L-929 C ells, A cta P h a rm ac o l. T o x ic o l., 35 (1974) 103. 3 R .G . Ham and W .L . M cKeehan. M edia and grow th requirem ents, in W .B . Jakoby and I.H . P a sta a^ S (E ds.) M ethods in Enzym oiogy Vol. LV1II, A cadem ic Press. New Y ork, 1979. 6 C . Shipm an, J r., T rypsin, A: m am m alian tissues, in P .J . Kruse, J r. and M .K . Patterson, Tissue C ulture M ethods and A pplications, Academic Press, New Y ork, 1973. 7 A .B . Pardee, A restriction point for control o f norm al anim al cell proliferation, Proc. N a tl., Sci. U S A , 71 (1974) 1286. 8 B. G retchen and R. Yam chesky, A u to rad io g rap h y , in W .B . Ja k o b y a n d l.H . P astan (Eds.) M ethod^ in E nzym oiogy, Vol. LV1I1, Academ ic Press. New Y ork. 1979. 9 R .L .P . A dam s, in Cell C ulture for Biochem ists. E lsev ier/N o rth -H o llan d , A m sterdam , 1980, p . ; 10 H .N . M un ro and A . Fleck, Recent developm ent in the m easurem ent o f nucleic acids in biolog m aterial. A n aly st, 91 (1966) 78. 11 O .H . L ow ry, N .J . R o seb ro u g h . A .L . F a rr and R .J . R a n d all, P ro te in m easurem ent with the f o ^ p h enol reag en t, J . B iol. C h em ., 193 (1951). 265-275. 12 E . G ern er, R . M eyn a n d R. H u m p h rey , N on-histone p ro tein synthesis d u rin g G t phase and its re tion to O N A replication, J. Cell P hysiol., 87 (1976) 277. 13 W .N . H itte lm a n a n d P .N . R ao , M apping G< p hase by p hase s tru c tu ra l m o rp h o lo g y o f p re condensed chrom osom es, J . Cell P hysiol., 95 (1978) 333. TOXLett. 15 AMITRO OF THE MICE (NOD me SATORU N OHHARA. Aburahi Ll geearch U (Received S (Accepted ( SUMMAR' Strain dii in N O D . 1C i m onths.. but not in c HOD stratr strain is m< IN T R O D l It is v, susceptii differen tibility t immunn derived by diabt in NOD ,\mit: it has be 2472 4T^ 9--X61S- fr * WORLD HEALTH ORGANIZATION INTERNATIONAL AGENCY FOR RESEARCH ON CANCER IARC MONOGRAPHS ON THE EVALUATION OF CARCINOGENIC RISKS TO HUMANS Overall E valuations o f Carcinogenicity: An Updating o f I A R C M onographs V olum es 1 to 42 SUPPLEM ENT7 This publication represents the views and expert opinions of an IARC ad-hoc Working Group on the Evaluation of Carcinogenic Risks to Humans, which met in Lyon, 10-18 March 1987 1987 2474 PREAMBLE 31 Limited evidence o f carcinogenicity: The data suggest a carcinogenic effect but are limited for making a definitive evaluation because, e.g., (a) the evidence of carcinogenicity is restricted to a single experiment; or (b) there are unresolved questions regarding the adequacy of the design, conduct or interpretation of the study; or (c) the agent increases the incidence only of benign neoplasms or lesions of uncertain neoplastic potential, or of certain neoplasms which may occur spontaneously in high incidences in certain strains. Inadequate evidence o f carcinogenicity: The studies cannot be interpreted as showing either the presence or absence of a carcinogenic effect because of major qualitative or quantitative limitations. Evidence suggesting lack o f carcinogenicity: Adequate studies involving at least two species are available which show that, within the limits of the tests used, the agent is not carcinogenic. A conclusion of evidence suggesting lack of carcinogenicity is inevitably limited to the species, tumour sites and doses of exposure studied. (iii) Supporting evidence o f carcinogenicity The other relevant data judged to be of sufficient importance as to affect the making of the overall evaluation are indicated. (b) Overall evaluation Finally, the total body of evidence is taken into account; the agent is described according to the wording of one of the following categories, and the designated group is given. The categorization of an agent is a matter of scientific judgement, reflecting the strength of the evidence derived from studies in humans and in experimental animals and from other relevant data. Group I -- The agent is carcinogenic to humans. This category is used only when there is sufficient evidence of carcinogenicity in humans. Group 2 This category includes agents for which, at one extreme, the degree of evidence of carcinogenicity in humans is almost sufficient, as well as agents for which, at the other extreme, there are no human data but for which there is experimental evidence of carcinogenicity. Agents are assigned to either 2A (probably carcinogenic) or 2B (possibly carcinogenic) on the basis of epidemiological, experimental and other relevant data. Group 2A -- The agent is probably carcinogenic to humans. This category is used when there is lim ited evidence of carcinogenicity in humans and sufficient evidence of carcinogenicity in experimental animals. Exceptionally, an agent may be classified into this category solely on the basis of limited evidence of carcinogenicity in humans or of sufficient evidence of carcinogenicity in experimental animals strengthened by supporting evidence from other relevant data. 32 IARC MONOGRAPHS SUPPLEMENT 7 Group 2B -- The agent is possibly carcinogenic to humans. This category is generally used for agents for which there is limited evidence in humans in the absence of sufficient evidence in experimental animals. It may also be used when there is inadequate evidence of carcinogenicity in humans or when human data are nonexistent but there is sufficient evidence of carcinogenicity in experimental animals. In some instances, an agent for which there is inadequate evidence or no data in humans but limited evidence of carcinogenicity in experimental animals together with supporting evidence from other relevant data may be placed in this group. Group 3 -- The agent is not classifiable as to its carcinogenicity to humans. Agents are placed in this category when they do not fall into any other group. Group 4 -- The agent is probably not carcinogenic to humans. This category is used for agents for which there is evidence suggesting lack o f carcinogenicity in humans together with evidence suggesting lack o f carcinogenicity in experimental animals. In some circumstances, agents for which there is inadequate evidence of or no data on carcinogenicity in humans but evidence suggesting lack o f carcinogenicity in experimental animals, consistently and strongly supported by a broad range of other relevant data, may be classified in this group. References 1. IARC (1977) IARC Monographs Programme on the Evaluation o f the Carcinogenic Risk of Chemicals to Humans. Preamble (IARC intern, tech. Rep. No. 77/002), Lyon 2. IARC (1978) Chemicals with Sufficient Evidence of Carcinogenicity in ExperimentalAnimals -- IARC Monographs Volumes 1-17 (IARC intern, tech. Rep. No. 78/003), Lyon 3. IARC (1979) Criteria to Select Chemicalsfor IARC Monographs (IARC intern, tech. Rep. No. 79/003), Lyon 4. IARC (1982) IARC Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans, Supplement 4, Chemicals, Industrial Processes and Industries Associated with Cancer in Humans (IARC Monographs. Volumes l to 29), Lyon 5. IARC (1983) Approaches to Classifying Chemical Carcinogens According to Mechanism of Action (IARC intern, tech. Rep. No. 83/001), Lyon 6. IARC (1973-1984) Information Bulletin on the Survey of Chemicals Being Tested for Carcinogenicity, Numbers 1-12, Lyon Number 1 (1973) 52 pages Number 2 (1973) 77 pages Number 3 (1974) 67 pages Number 4 (1974) 97 pages Number 5 (1975) 88 pages Number 6 (1976) 360 pages 1S6 IARC MONOGRAPHS SUPPLEMENT 7 mutagenicity in bacteria. Pentachlorophenol did not induce strand breaks in DNA from bacteriophage. It gave negative results in a host-mediated assay with mice using bacteria as indicators7. 2,4,6-Trichlorophenol induced somatic mutations in the spot test in mice in vivo. It induced mutation but not gene conversion or crossing-over in yeast and was not mutagenic to bacteria7. Neither 2,3,4,6-tetrachlorophenol nor 2,4,5-trichlorophenol was mutagenic to bacteria7. References 1IARC Monographs, 41, 319-356, 1986 2Pearce, N.E.. Sheppard, R.A., Smith, A.H. & Teague, C.A. (1987) Non-Hodgkin's lymphoma and farming: an expanded case-control study. Int. J. Cancer, 39, 155-161 ]Woods, J.S., Polissar, L., Severson, R.K., Heuser, L.S. &Kulander, B.G.( 1987) Soft tissue sarcoma and non-Hodgkin's lymphoma in relation to phenoxy herbicide and chlorinated phenol expo sure in western Washington. J. nail Cancer Inst, 78, 899-910 MARC Monographs, 20, 303-325, 1979 MARC Monographs, 20, 349-367, 1979 `National Cancer Institute (1979) Bioassay of 2,4,6-Trichlorophenol for Possible Carcinogenicity ( Tech. Rep. Ser. No. 155; DHEW Publ. No. (NIH) 79-1711), Washington DC, US Department of Health, Education, and Welfare MARC Monographs, Suppl. 6, 231-232, 445-447, 517-518, 533-537, 1987 CHLOROPHENOXY HERBICIDES (Group 2B) A. Evidence for carcinogenicity to humans (limited) In a Danish cohort study of chemical workers exposed to chlorophenoxy herbicides [particularly (4-chloro-2-methylphenoxy)acetic acid (MCPA), 2-(4-chloro-2-methylphenoxy>propanoic acid (mecoprop), 2,4-dichlorophenoxyacetic acid (2,4-D) and 2-{2,4-dichlorophenoxy)propanoic acid (dichlorprop)], as well as other chemicals, no overall increase in cancer incidence rate was observed, but there were significantly increased risks for softtissue sarcoma and lung cancer in some subcohorts, which were not necessarily those with the highest exposures to chlorophenoxy herbicide preparations1. A recently reported cohort of 5784 male employees in a UK company that manufac tured, formulated and sprayed MCPA and other pesticides, but only small amounts of 2,4,5-trichlorophenoxyacetic acid (2,4,5-T), had no general excess mortality from cancer. Three potentially exposed workers died from nasal carcinoma, however. One death due to soft-tissue sarcoma approximately equalled the expected rate. No excess of lymphoma was seen2. A Finnish cohort study of brush control workers with short follow-up time showed no increased cancer risk. A small Swedish cohort study of railroad workers who sprayed herbicides showed an increased risk of cancers at all sites combined for those exposed to chlorophenoxy herbicide preparations and other herbicides. An excess incidence of all 2477Ji> CHLOROPHENOXY HERBICIDES 157 cancers was also reported from a very small cohort of Swedish forestry foremen exposed to chlorophenoxy herbicide preparations and other herbicides. A study of long-term pesticide applicators in the German Democratic Republic, heavily exposed to a number of chemicals, including 2,4-D and MCPA, demonstrated an increased risk of bronchial carcinoma1. Two population-based case-control studies conducted in northern and southern Sweden, respectively, showed a statistically significant association between exposure to chlorophenoxy herbicides, especially in forestry and agriculture, and the occurrence of soft-tissue sarcomas. An increased risk of soft-tissue sarcoma was described among highly exposed Italian rice weeders in a population-based case-control study. However, a casecontrol study from New Zealand did not demonstrate any increased risk of soft-tissue sarcoma in people exposed to chlorophenoxy herbicides1. Nor did a recently reported population-based case-control study of soft-tissue sarcoma and lymphoma in Kansas, USA, find any association between soft-tissue sarcoma and exposure to 2,4-D3. A statistically significant association between malignant lymphoma (Hodgkin's and non-Hodgkin's) and exposure to chlorophenoxy herbicides was found in a Swedish casecontrol study1. The population-based case-control study of soft-tissue sarcoma and Hodgkin's and non-Hodgkin's lymphoma in Kansas showed that use of 2,4-D was associated with non-Hodgkin's lymphoma, especially among farmers who had been exposed for more than 20 days per year, among whom there was an approximately six-fold excess, and among those who had mixed or applied the herbicides themselves. Hodgkin's lymphoma was not, however, found to be associated with herbicide exposure3. No significant or consistent association was seen in a case-control study of these tumours from New Zealand, and in a Danish cohort of chemical workers exposed to chlorophenoxy herbicides there was also no significantly increased risk of malignant lymphoma1'4. Fanners and forestry workers in Washington State, USA, with exposure to phenoxy herbicides had a significantly increased risk of non-Hodgkin's lymphoma. People of Scandinavian descent in the area had an increased risk of soft-tissue sarcoma in connection with phenoxy herbicide exposure, but no increased risk of non-Hodgkin's lymphoma3. Three Swedish case-control studies of colon, liver, and nasal and nasopharyngeal cancer, which used the same study design and methods as in the studies on soft-tissue sarcoma and malignant lymphoma, did not demonstrate significantly increased risks, although a risk ratio of 2.1 was reached for nasal and nasopharyngeal cancer1. A record-linkage study using census data on occupation and cancer registry information in Sweden did not reveal any excess of soft-tissue sarcoma among agricultural and forestry workers6-7. However, on the basis of occupational titles, the elevated risks seen in Swedish case-control studies of soft-tissue sarcoma and lymphoma were reduced to 1.4 or less8. A UK study based on data from cancer registration showed a slightly but significantly increased risk of soft-tissue sarcoma among farmers, farm managers and market gardeners, but not in other subgroups in forestry and farming9. No association with soft-tissue sarcoma has been found with military service in Viet Nam, despite potential exposure to phenoxy herbicides1*10, although there is a case report in this respect1. 158 IARC MONOGRAPHS SUPPLEMENT 7 B. Evidence for carcinogenicity to animals (inadequate for 2,4-D and 2,4,5-T) 2.4- D and several of its esters were tested in rats and mice by oral administration and in mice by subcutaneous administration. All of these studies had limitations, due either to inadequate reporting or to the small number of animals used. Therefore, although increased incidences of tumours were observed in one study in which rats received 2,4-D orally and in another in which mice received its isooctyl ester by subcutaneous injection, no evaluation of the carcinogenicity of this compound could be made11. 2,4,5-T was tested in mice by oral and subcutaneous administration. All of the studies had limitations due to the small numbers of animals used. Therefore, although an increased incidence of tumours at various sites was observed in one study in which 2,4,5-T (containing less than 0.05 mg/ kg chlorinated dibenzodioxins) was given orally, no evaluation of the carcinogenicity of this compound could be made on the basis of the available data12. In rats fed diets containing three different concentrations of 2,4,5-T, the incidences of all tumour types were comparable to those in the control groups, with the exception that the incidence of interfollicular C-cell adenomas of the thyroid was increased significantly in female rats receiving the lowest dose. This increase was not considered to be related to treatment since it was not dose-related and the female control group had an unusually low incidence of thyroid adenomas12. A study of the incidence of small-intestinal adenocarcinoma in groups of sheep from different farms showed an association with use of phenoxy herbicides, as elicited by farmers' responses to a questionnaire. However, other herbicides were in use, and there was no documentation of exposures14. No adequate data were available on the carcinogenicity of MCPA1S. C. Other relevant data In single studies, lymphocytes of persons occupationally exposed to chlorophenoxy herbicides, including 2,4-D, did not show increased frequencies of sister chromatid exchanges or chromosomal aberrations. Other studies could not be assessed since workers were also exposed to other formulations. A single study of herbicide and pesticide sprayers exposed to 2,4,5-T, in which a small increase in the incidence of sister chromatid exchanges was reported, could not be assessed since workers were also exposed to other formulations. Persons occupationally exposed to MCPA did not have increased frequencies of sister chromatid exchanges (one study) or chromosomal aberrations in their lymphocytes16. 2.4- D did not induce dominant lethal mutations, micronuclei or sister chromatid exchanges in rodents treated in vivo. Pure 2,4-D did not induce chromosomal aberrations in human lymphocytes in vitro, whereas a commercial formulation did. 2,4-D induced sister chromatid exchanges and unscheduled DNA synthesis in human cells in vitro. It did not induce sister chromatid exchanges but did induce mutation and inhibited intercellular communication in Chinese hamster cells in vitro. 2,4-D induced somatic mutation in Drosophila, but conflicting results were obtained for induction of sex-linked recessive lethal mutations; it did not induce aneuploidy. 2,4-D caused chromosomal aberrations and was l 2479 AA>) rp nd in ;er to eased ndin on o f udies eased .ining )f the nrats mour Jence e rats nee it :ce o f from mers' as no enoxy matid irkers -ayers anges tions. sister 6. matid ons in sister id not .llular ion in lethal d was CHLOROPHENOXY HERBICIDES 159 mutagenic in plants. It induced mutation, gene conversion and mitotic recombination in yeast. It was not mutagenic to bacteria or bacteriophage. The n-butyl and iso-octyl esters of 2,4-D were also not mutagenic to bacteria16. 2,4,5-T induced chromosomal aberrations in bone-marrow cells of Mongolian gerbils, but not in spermatogonia of Chinese hamsters, and aneuploidy in oocytes of rats treated in vivo. It did not induce micronuclei in mice or dominant lethal mutations in mice or rats in vivo. 2,4,5-T inhibited intercellular communication in Chinese hamster V79 cells in vitro. There was weak evidence for the induction of sex-linked recessive lethal mutations in Drosophila; it did not induce aneuploidy or somatic mutation. It induced chromosomal aberrations in plants. It was mutagenic to yeast, but neither 2,4,5-T nor the n-butyl-, /jo-butyl or iso-octyl ester of 2,4,5-T was mutagenic to bacteria16. MCPA did not induce structural chromosomal aberrations or micronuclei in mice treated in vivo; weakly positive results were obtained for sister chromatid exchanges in cells of Chinese hamsters treated in vivo and in vitro. It was weakly active in inducing sex-linked recessive lethal mutations but did not induce aneuploidy in Drosophila. MCPA and its methyl ester were mutagenic to yeast but not to bacteria16. References XIARC Monographs, 41, 357-406, 1986 2Coggon, D., Pannett, B,, Winter, P.D., Acheson, E.D. & Bonsall, J. (1986) Mortality of workers exposed to 2-methyl-4-chlorophenoxyaceticacid. Scand. J. Work Environ. Health, 12,448-454 3Hoar, S.K., Blair, A., Holmes, F.F., Boysen, C.D., Robel, RJ., Hoover, R. & Fraumeni, J.F., Jr (1986) Agricultural herbicide use and risk of lymphoma and soft-tissue sarcoma. J. Am. med. Assoc., 256, 1141-1147 `Pearce, N.E., Sheppard, R.A., Smith, A.H. & Teague, C.A. (1987) Non-Hodgkin's lymphoma and farming: an expanded case-control study. Ini. J. Cancer, 39, 155-161 5Woods, J.S., Polissar, L., Severson, R.K., Heuser, L.S. & Kulander, B.G. (1987) Soft tissue sarcoma and non-Hodgkin's lymphoma in relation to phenoxy herbicide and chlorinated phenol exposure in western Washington. J. nail Cancer Inst., 78, 899-910 `Wirklund, X. & Holm, L.-E. (1986) Soft tissue sarcoma risk in Swedish agricultural and forestry workers. J. nail Cancer Inst., 76, 229-234 7Wirklung, K,, Holm. L.-E. & Dich, J. (1987) Soft tissue sarcoma risk among agricultural and forestry workers in Sweden. Chemosphere (in press) 8Hardell, L. & Axelson, O. (1986) Phenoxyherbicides and other pesticides in the etiology of cancer: some comments on Swedish experiences. In: Becker, C.E. & Coye, M.J., eds. Cancer Prevention. Strategies in the Workplace, Washington DC, Hemisphere, pp. 107-119 'Balarajan, R. & Acheson, E.D. (1984) Soft tissue sarcomas in agriculture and forestry workers. J. Epidemiol. Commun. Health, 38, 113-116 Kang, H.K., Weatherbee, L., Breslin. P.P.. Lee, Y. &Shepard. B.M. (1986) Soft tissue sarcomas and military service in Vietnam: a case comparison group analysis of hospital patients. J. occup. Med., 28, 1215-1218 "ARC Monographs. 13, 111-138, 1977 'ARC Monographs, 15. 273-299, 1977 160 IARC MONOGRAPHS SUPPLEMENT 7 13Kociba, R.J., Keyes, D.G., Lisowe, R.W., Kalnins, R.P., Dittenber, D.D., Wade, C.E., Gorzinski, S.J., Mahle, N.H. & Schweiz, B.A. (1979) Results of a two-year chronic toxicity and oncogenic study of rats ingesting diets containing 2,4,5-trichlorophenoxyacetic acid (2,4,5-T). Food Cosmet. Toxicol., 17, 205-221 14Newell, K.W., Ross, A.D. & Renner, R.M. (1984) Phenoxy and picolinic acid herbicides and small intestinal adenocarcinoma in sheep. Lancet, ii, 1301-1305 1>IARC Monographs, 30, 255-269, 1983 "IARC Monographs, SuppL 6, 161-163, 233-236, 538-540, 1987 CHLOROPRENE (Group 3) A. Evidence for carcinogenicity to humans (inadequate) In one study, an excess o f lung and skin cancers was related to occupational exposure to chloroprene. In another investigation, no excess of lung or other type of cancer was reported among chloroprene workers. There is one case report of an angiosarcoma of the liver in a worker exposed to chloroprene1. B. Evidence for carcinogenicity to animals (inadequate) A number of experimental studies were considered to be inadequate for an evaluation of the carcinogenicity of chloroprene1. In a further study2 in which chloroprene was given orally to pregnant rats and their offspring were treated for life, by stomach tube, the total incidence of tumours was similar in treated and untreated animals. C. Other relevant data An increased incidence of chromosomal aberrations was found in the lymphocytes of workers exposed to chloroprene3. Chloroprene induced dominant lethal mutations in rats and chromosomal aberrations in bone-marrow cells of mice treated in vivo. It induced transformation in one hamster cell line but did not induce mutation in Chinese hamster cells. It induced sex-linked recessive lethal mutations in Drosophila and was mutagenic to bacteria3. References 'ARC Monographs, 19, 131-156, 1979 2Ponomarkov, V. & Tomatis, L. (1980) Long-term testing of vinylidene chloride and chloroprene for carcinogenicity in rats. Oncology, 37, 136-141 >IARC Monographs, Suppl. 6, 164-165, 1987 2482 $ v d e o t a p e s n o w availae 1ST ANNUAL SCIENTIFIC ASSEMB ON ENVIRONMENTAL HEALTH October 7-8,1988 New Orleans, LA Sponsored by Citizens Clearinghouse for Hazardous Wastes Louisiana Environmental Action Network Ohio State University College of Medicine TAPE #1 Opening Remarks Lois Gibbs, Executive Director, CCHW Dr. Gary Gillen, Ohio State Univ College of Medicine Richard Miller, Oil, Chemical & Atomic Workers Routes of Exposure Stephen Lester, Science Director, CCHW Dr. Beverly Paigen, Oakland Childrens Hospital Dr. Paul Templet, Director, Louisiana Dept. Envir. Quality The Politics of Cancer Dr. Samuel Epstein, Univ Illinois School of Public Health TAPE #2 How Chemicals Affect Health Dr. David Ozonoff, Boston Univ School of Medicine Taking a Medical and Exposure History Dr. Marvin Legator, Univ Texas Medical Branch Dr. Beverly Paigen, Oakland Childrens Hospital TAPE #3 Reproductive Toxicity Dr. Maureen Paul, Univ Mass Medical School How To Get Doctors Involved Dr. Gary Gillen, Ohio State Univ College of Medicine Will Collette, CCHW TAPE #4 Federal State/Involvement Penny Newman, CCHW Health Studies Dr. Marvin Legator, Univ Texas Medical Branch Penny Newman, CCHW TAPE #5 How To Get Help/Treatment Dr. Kenneth Miller, Oil, Chemical & Atomic Workers The Sociological Impact of Exposure to Toxic Chemicals Dr. Beverly Wright, Univ New Orleans The Legal Rights of Victims Dr. Earon Davis, Eco-IUness Law Report TAPE #6 Neurotoxicity Dr. Janette Sherman, Toxicologist TAPE #7 Case Studies: Selrisim, Lowell, MA Dr. David Ozonoff, Boston Univ Sch Med Love Canal, Niagara Falls, NY Dr. Beverly Paigen, Oakland Childrens Hospital Tapes can be ordered from Citizens Clearinghouse for Hazardous Wastes, Inc. P.O. Box 926, Arlington, VA 22216 (703)276-7070 Tapes are available on VHS format only for $14.95 plus $2 postage and handling. The complete set can be purchased for $65 plus $5 postage and handling. 2483 V to rY O' YES! I want to continue to receive Environmental Health Monthly. Name__ Address. We count on your support for Environmental Health Monthly. Annual Subscription Rates: O S35 Health Professionals O $15 Grassroots Community People O Check Enclosed or O Charge to my credit card: Visa/Mastercard Expiration Date Signature --------------------------------------------- - CCHW is a non-profit tax-exempt organization that serves as an Environmental Crisis Center. Environmental Health Monthly was established to provide a forum to educate and inform health professionals and community leaders on current scientific knowledge on environmental health issues. Environmental Health Monthly is published by CCHW. All reprinted articles are reviewed by the EHM Review Board and reprinted with permission of authors or publishers. Comments or suggestions for articles are encouraged and should be . submitted to Stephen Lester, 5 Managing Editor, EHM, P .0 .926 Arlington, VA 22216 (703) 276-7070. V____________________________ J -1 Citizens Clearinghouse for Hazardous Wastes, Inc. P.O. Box 926 Arlington, VA 22216 (703) 276-7070 PRAY FOR PEACE _ Environmental Health Monthly 2485 8 United States Department of Agriculture Forest Service Pacific Northwest Region November 1988 px# ^ S t- Managing Competing f and Unwanted > Vegetation Final Environmental Impact Statement Appendices D & H 4-,o 8 I HlS.kASa( I h. n- H-W O M N I E nvironm ental Services 1987. P relim inary health effects evaluation for pollu tan ts gener ated by field burning, slash b u rning and residential w ood com ubustion. M ay P repared for O regon State D epartm ent of E nvironm ental Q uality. O regon State D epartm ent of Environm ental Q uality (O regon DEQ) June 1986. Field a n d slash burning PM -10/T SP m axim um Im pact study. O regon State D epartm ent of Environm ental Q uality (O regon DEQ) F ebruary 1987. O regon toxic air pollutant em issions Inventory. O z k ay n a k , H ., a n d S pengler, J.D. February 1986. H ealth effects of airborne particles. E nergy and E n v iro n m en tal Policy C en ter, Jo h n F. K en n ed y S chool o f G o v e rn m ent, H arvard U niversity, C am bridge. Pearce, N .E., S m ith, A .H . e t al. 1986. N o n -H o d g k ln 's lym phom a an d exposure to phenoxyherbid d e s, chlorophenols, fencing w ork, and m eat w orks em ploy m en t: a case-co n tro l stu d y . Br. J. In d u str. M ed. 43:75-83. P e terso n , S. 1983. G razing Im pacts on bacterial w ater quality - Alsea ranger district. P re p a re d for th e U.S.D.A. Forest Service, R egion VI. R adian C orporation F eb ru ary 1986. W ash in gton toxic a ir co n tam in an ts stu d y -rev ised final report. P repared for W ashington State D epartm ent of T o x ic o lo g y . R iih im a ld , V ., A s p , S., a n d S v en , 1! 1982. M ortality o f 2,4-D acid a n d 2,4,5-T acid h erb icid e ap p lic a to rs in F in la n d . S c a n d . J. W o rk E n v iro n . H e a lth 8:37-42. S m ith, A.H. et al. 1984. Soft tissue sarcom a an d exposure to p henoxyhcrbicides an d c h lo ro p h e n o ls in N e w Z e a la n d . JN C I 73(5): i l l 1-17. T h ie ss, A .M ., F re n tze l-B e y m e, R. a n d L ink, R. 1982. M ortality Study of persons exposed to dioxin in a trichlorophenol-process accident that occurred in the BASF A C on N o v e m b e r 17,1953. A m . J. In d . M e d . 3:179-89. U.S. E n v iro n m en tal P ro tectio n A gency (USEPA) 1976. Interim p ro ced u res an d g u id elin es for health risks and econom ic im pact assessm ents of suspected carcinogens. Eederal R egister 41: 21402-21405. U.S. E n v iro n m en tal P ro tectio n A gency (USEPA) 1984. P ro p o sed g u id elin es for carcin o g en risk assessm ent; for exposure assessm ent; for m utagenicity risk assessm ent; for health assessm ent of suspect developm ental toxicants. Federal R egister 49L 46294-46301; 46304-46312; 46314-46321; a n d 4632446331 (N o v em b er 23,1984). Z ack, J.A. a n d G affey, W .R. 1983. A m o rtality stu d y of w o rk ers em p lo y ed at the m o n san to co m p an y p lan t in N itro, W est V irginia. E nviron. Sci. Res. 26:575591. Z ack, J.A., a n d S u sk in d , R.R. 1980. T he m o rtality ex p erien ce o f w o rk ers exposed to tetrachlorodibenzodioxin in a trichlorophenol process accident. JOM 22(1 ):11-14. HOU S G O V E F IN M E N I P R iN U N G O F F IC E I 0 M - 0 1 0 5 0 - 6 0 7 1 1 R E G IO N to I IlUilIlIUUMI I lOUlitt H Risk >y sment r M-1M Bibliography-H ealth Risk/Epidem iology A m es, B.N., M agaw , R., a n d G old, L S. 1987. R anking possible carcinogenic hazards. Science 236:271-280. A xelson, O . e t aL 1980. H e rb icid e e x p o su re a n d tu m o r m o rtality . S can d J. W ork E nviron. H ealth 6:73-79. C a la b rese, E.J. 1983. Scaling: a n a tte m p t to And a com m on den o m in ato r. In: "P rin c ip le s o f an im a l ex trap o latio n ," ed . C alab rese, E.J., N e w Y o rk , J. W ile y 8c S o n s. p p . 499-527. C alifornia A ir Resources Board D ecem ber 1981. In fo rm atio n relating to d ev elo p m en t o f a state am bient a ir quality stan d ard for fine o r inhalable particulates. C ru m p , K.S., a n d C o m p an y , Inc. 1986. W orst case analysis stu d y o f forest p lan tatio n herbicide use. M ay. P repared for Forest Land M anagem ent Division, D epart m ent o f N atu ral Resources, S tate of W ashington. D av id so n , I.W ., P a rk e r, J.C ., a n d Bellies, R.P. 1986. Biological basis for extrapolation across m am m alian sp e cies. R eg u lato ry Toxicol. P h arm acol. 6:211-237. D ost, F.N. S eptem ber 17,1986. A n estim ate of carcinogenic risk associated w ith polyarom atic hydrocarbons in sm oke from prescribed burning in forestry. Subm itted to Bureau of Land M anagem ent, W ash in g to n D.C. F lngerhut, M .A. et al. 1984. Review of exposure an d pathology d ata for seven cases reported as soft tissue sarcom a am ong persons occupationally e x p o sed to dioxin-contam inated herbicides. In: "P ublic health risks o f th e d io x in s," ed. L ow rance, W .W ., Los A ltos, C A , K aufm ann. p p . 187-203. H a rd ell, L., a n d E riksson, M. 1981. Soft tissue sarcom as, phenoxy herbicides an d ch lorinated p h e n o ls. L ancet (A u g u st 1): 250. .H um an Epic i H a rd e ll, L., E rik sso n , M ., L e n n c r, P., a n d L u n d g re n , E. 1981. M alig n an t ly m p h o m a a n d e x p o su re to chem icals, especially organic solvents, chlorophenols and phenoxy acids: a casec o n tro l s tu d y . Br. J. C a n c e r 43:169-76. H a rd e ll, L. a n d S a n d s tro m , A. 1979. C ase-control stu d y : so ft-tissu e sarco m as a n d ex p o su re to p h en o x y acetic a cid s o r c h lo ro p h e n o ls. Br. j. C a n ce r 39:711-17. H a rt, R .W ., a n d F ish b e in , L. 1985. Interspecies extrap o latio n of d ru g an d genetic toxicity d ata. In: "T oxicological R isk A ssessm en t Voi. I," eds. C lay so n , D.B., K re w s k i, D ., a n d M u n ro , 1., B oca R a to n , FL, C R C P re ss , p p . 3-40. H oar, S.K., et al. 1986. A gricultural h erb icid e u se an d risk of ly m p h o m a an d soft tissue sarcom a. JA M A 256(9): 1141-1147. H o n ch ar, P.A ., a n d H alp erin , W.E. 1981. 2,4,5-T, trich lo ro p h en o l a n d soft tissu e sarcom a. L ancet (January 31):268-9. L ynge, E. 1985. A follow -up stu d y of can cer incidence am o n g w orkers in m a n u fa c tu re o f p h e n o x y h e rb ic id e s in D e n m ark . Br. J. C a n ce r 52:259-70. M u rp h y , S.D. 1986. Introduction an d historical perspective of risk assessm ent. W ash in g to n Public H ealth 6(1):7-12. N ational Research C ouncil--C om m ittee on the Institutional M eans for A ssessm ent of Risks to Public H ealth (NRC C om m ittee) 1983. Risk assessm en t in the federal go v ern m ent: m anaging the process. W ash in g to n D.C., N atio n al A cadem y Press. N ew to n , M ., an d D ost, F.N. 1984. Biological a n d physical effects of forest vegetation m anage m ent. S eptem ber 24, State of W ashington, D epartm ent of N atural Resources, O lym pia. O ffice of Science a n d T echnology Policy (OSTP) 1984. C h em ical carcinogens: rev iew o f th e sciences a n d its associ a ted principles. Federal R egister 49: 21595-21601. c\ O Human Epidemiology sprayers in New Zealand and controls. exposed t 352 not exposed one before or after conception. 1 defect and 0.89 risk of only in the exposed group. t palate occurrence by county herbicide use by county based ice acreage. No association rved. enital malformation and 245-T ever time in Hungary. No elation observed. Zealand malformations in dati o n with spraying icides by area and time. Mixed -Its ralia - neural-tube defects and ying of 2,4,5-T over time. Mild rive association and & Whales - malformations occupations with likely sure to 2,4,5-T. racial cleft -maiion consistently high, lifida high in gardeners and ...itural workers. Anencephaiy . in gardeners. Association are _ew of Vietnamese studies for . paternal and maternal studies :-d positive results - nc clear iern ,ew of reproductive effects cf sins/ no definite conclusions. NEUROLOGICAL EFFECTS ----------------------- Cohort Studies----------------------- Singer, Moses et al 1982 56 workers in a 2,4-D & 2,4,5-T plant were compared with 25 unexposed controls. Median motor, median sensory and sural nerve velocities were measured. 46% of exposed group had slowed velocities compared to 5% in the control group (pc.001). The mean velocities of the median motor and sural nerves were significantly slower than the controls. There was a highly significant inverse relation between the sural nerve velocity and length of employment. All these relationships remained true when adjusted for alcohol consumption, age and other parameters. Suskind t Hertzberg 1984 204 workers at Monsanto's Nitro, West Virginia plant exposed to dioxin and 163 workers not exposed. Nerve conduction velocities in ulnar and peroneal nerves was non- significantly reduced in exposed group. Sural nerve conduction was slightly reduced in unexposed. ANIMAL STUDIES SHEEP AND SMALL INTESTINAL ADENOCARCINOMA Newell, Ross & Renner Sheep from 88 farms in New Zeal {3 2 0 , 6 7 8 female sheep/ 1 2 5 cases ** ( 6 / 1 0 0 0 ) from 61 farms Exposure to phenoxy herbicides, picolinic herbicide and combined. Significant positive trends for treatment of feed with either herbicide or both combined, and with how recently the feed had beer. treated before consumption. 2488 H-I43 HHR iusmk aAnssHeesaslmthe n t REPRODUCTIVE OUTCOMES * Cohort Studies Smith, Fischer, Pearce 548 sprayers in New Zealand and & Chapman 1982 441 controls. 427 exposed & 352 not exposed one year before or after conception. Exposed group had 1.19 RR of congenital defect and 0.89 risk of miscarriage. Stillbirths (3) occurred only in the exposed group. Nelson et al 1979 Thomas 1980 Hanify et al 1980 Field &Kerr 1979 Balarajan & McDowall Other Studies----------------------- Cleft palate occurrence by county with herbicide use by county based on rice acreage. No association observed. Congenital malformation and 245-T use over time in Hungary. No association observed. New Zealand malformations in association with spraying herbicides by area and time. Mix>_-results Australia - neural-tube defects ar.c spraying of 2,4,5-T over time.Milo positive association England & Whales - malformations and occupations with likely exposure to 2,4,5-T. Facial cleft malformation consistently high. Spina bifida high in gardeners ar.c agricultural workers. Anencep'naly high in gardeners. Association are soft. Erikson et al 1984 Hatch 1984 H-142 Review of Vietnamese studies for both paternal and maternal studies Mixed positive results - no clear pattern Review of reproductive effects c-f dioxins/ no definite conclusions. 2489 9- 7/ TOXICITY/ STUDY POINT ESTIMATE OF RELATIVE RISK >1.0 <=1.0 COMMENT SOFT TISSUE SARCOMA (STS) -- Case-Report------------- *--------- ^ Cook 1981 Case report/ one more STS case discovered in the Dow cohort *-. described in Cook, Townsend & Ott. Moses & Selikoff 1981 Case report/ one more STS case discovered in the Monsanto cohort. Johnson, Kugler & Brown 1981 Case reports/ two more STS cases with work histories at Monsanto/ not identified a part of above cohorts. Other Studies Milham 1982 1.2 Proportional Mortality Death certificate study/ 49 STS deaths/ looked at occupations with possible 2,4-D exposure including farming and forestry. . . > > s v'-' ' > Jk 9^ O ' ** $ 3 0 H-X141 'r F^ S e - TOXICT/ cmnv POINT ESTIMATE OF RELATIVE'1^- >1 _Q COMMENT SOFT TISSUE SARCOMA (STS) -Cohort Studies---- -*------ --- -- Lynge 1985 2.72 Based on 5 male cases. - 0.0 Based on 0 female cases. 3.33 Based on 1 male case in pl acid manufacturing and pat 0.0 Based on 0 female cases in] acid manufacturing and pac 5.19* Based on 3 male cases in manual services. v 0.0 Based on 0 female cases in manual, services. Zack & Gaffey 1983 1.38 Based on 1 male case in other chemical manufacturing and packing]' 0.0 Based on 0 female cases in other chemical manufacturing and packing. Based on 1 male death in plant. PMR based on 1 male death to a 245-T exposed worker. Riihimaki et al 1982 0.0 Based on 0 male deaths. Axelson et al 1980 Based on 1 male death. 0.0 Based on 0 male deaths with only phenoxy acid exposure. 0.0 Based on 0 male deaths with phenoxy acid & amitrole exposure. Based on 1 male death with only amitrole exposure (with ten year latency period). Ott et al 1980 0.0 Based on 0 male deaths. Honchar & Halperin 1981 41.4' Summary of the 4 USA studies (one unpublished at the time)/ total deaths=105/ three STS cases. Significant at the p=0.05 level, Unauantified excess risk. 0 (>> < 9-70 Human Epidemiology TOXICITY/ STUDY POINT ESTIMATE OF RELATIVE RISK >1.0 <=1.0 COMMENT SOFT TISSUE SARCOMA (STS) -------------- Case-Control Studies------ Hardell & Sandstrom 1979 5.3* 46 cases and 201 controls. Controls were from the general population. Cases & controls with chlorophenol exposures were excluded. Eriksson, Hardell et al 1981 6.8* 110 cases & 220 controls. Controls were from the general population Cases & controls with chlorophenol exposures were excluded. Smith, Pearce et al 1984 1.3 82 cases and 92 controls. Controls were selected from males with other cancers. Case & controls with chlorophenol exposures were excluded. Hoar, Blair et al 1986 0.9 71 cases and 948 controls. Controls were from the general population Exposure was based on reported herbicide use. Woods et al 1987 0.99 (0.0) ((-)) 576 cases and 694 random controls from the general population: ever exposed. (forestry herbicide applicator - no cases). ((15 years exposure 15 years prior to diagnosis - a latency response was demonstrated)) * = Significant at the p=0.05 level. - = No association (number not reported). 2492 P - 3-513H-139 HHR iusmk aAnssHeesaslmthe n t i?? TOXICITY/ STUDY POINT ESTIMATE OF RELATIVE RISK >1.0 <=1.0 COMMENT NON-HODGKIN' S Cohort Studies o o o ooo Riihimaki et al 1982 Based on 0 male deaths, AxeIson et al 1980 Based on 0 male deaths Ott et al 1980 Based on 0 male deaths. 2493 H-138 9-6>f Human Epi TOXICITY/ STUDY POINT ESTIMATE OF RELATIVE RISK >1.0 <*1.0 COMMENT NON-HODGKIN'S Hardell 1979 --------- Case-Report-----------------------Pilot study of 17 cases. 14 cases had employment consistent with exposure (farming, forestry, sawmill, painting and building). Hardell, Eriksson et al 1981 --- Case-Control Studies-------------------- 4.8* 169 cases of malignant lymphoma (including 109 non-Hodgkins lymphomas) and 338 controls. Controls were from the general population. Cases and controls with exposure to chlorophenol were excluded. A dose response was observed. SMR is reported for the entire group - it was reported that there was no observable difference in risk between the Hodgkin's and non- Hodgkin 's cases. Hardell 1981 5.5* 169 malignant lymphoma cases (including 109 non-Hodgkins lymphomas) and 154 controls. This is the same case population as above (Hardell & Eriksson 1981), but new controls were chosen from males with colon cancer. A dose response observed. SMR is reported for the entire cohort. Hoar, Blair et al 1986 1.6 (6.0*) 170 cases and 948 controls. Controls were from the general population. Exposure was based on reported herbicide use. (SMR increased to a significant 6.0 for herbicide use of at least 20 times per year). A dose response was demonstrated. Pearce, Smith et al 1986 1.4 83 cases matched with two sets of controls - 168 controls with other cancers and 228 controls from the general population. Woods et al 1987 1.07 576 cases and 694 random controls (4.80*) from the general population: ever ((1.71*) ) exposed. (forestry herbicide applicator). ((15 years exposure 15 years prior to diagnosis - a latency response was demonstrated)) = Significant at the p=0.05 level. 2494 H -137 Riihimaki et al 1982 Axelson et al 1980 Ott et al 1980 + Based on 1 male deaths with (+) only amitrole exposure (with ten year latency period). / Based on 0 male deaths. + = Unquantified excess risk 2495 H-136 9~& ?' Human Epidemiology tau*.-. TOXICITY/ J STUDY POINT ESTIMATE OF RELATIVE RISK >1 . 0 <=1.0 COMMENT HODGKIN'S -Case-Control Studies- Hardell, Eriksson et al 1981 4.8' 169 cases of malignant lymphoma (including 60 Hodgkins lymphomas) and 338 controls. Controls were from the general population. Cases and controls with exposure to chlorophenol were excluded. A dose response was observed. SMR is reported for the entire cohort - it was reported that there was no observable difference in risk between the Hodgkin's and non- Hodgkin's cases. Hardell 1981 5.5' 169 malignant lymphoma cases (including 60 Hodgkins lymphomas and 154 controls. This is the same case population as above (Hardell & Eriksson 1981), but new controls were chosen from males with colon cancer. A dose response observed. SMR is reported for the entire cohort. Hardell & Bengtsson 1983 5.0' 60 cases and 335 controls. Controls were from the general population. Cases & controls with high exposure to chlorophenols were excluded. This is a refinement of the two studies presented above (Hardell 1981 / Hardell et al 1981) Hoar, Blair et al 1986 0.9 71 cases and 984 controls. Controls were from the general population. Exposure was based on reported herbicide use. = Significant at the p=0.05 level. 2496 H -I35 1 HHR iusmk aAnssHeesaslmthe n t TOXICITY/ STUDY POINT ESTIMATE OF RELATIVE RISK >1.0 <1.0 COMMENT . LEUKEMIA Lynge 1985 Manufacturer Cohort 1.11 2.08 1.35 4.0 Riihimaki et al 1982 Herbicide Applicators Axelson et al 1980 Railroad Sprayers + + (+) (+) Ott et al 1980 Manufacturer Cohort* Cohort Studies Based on 5 male cases. Based on 2 female case. Based on 1 male case in phenoxy acid manufacture and packaging. Based on 1 female case in phenoxy acid manufacture and packaging. 0.0 Based on 0 male deaths with ten year latency period. Based on 2 male deaths. Based on 1 male deaths with only phenoxy acid exposure. (with a ten year latency period) Based on 1 male death with phenoxy acid and amitrole exposure, (with a ten year latency period) 0.0 Based on 0 male death. * = Significant at the p=0.05 level. + = Unquantified excess risk. 249^ H-I34 Human Epidemiology TOXICITY/ STUDY POINT ESTIMATE OF RELATIVE RISK >1.0 <=1.0 COMMENT STOMACH CANCER Cohort Studies Lynge 1985 Manufacturer Cohort 1.29 1.36 0.68 0.0 Based on 12 male cases. Based on 1 female case. Based on 2 male cases in phenoxy acid manufacture and packaging. Based on 0 female cases in phenoxy acid manufacture and packaging. Zack & Gaffey 1983 Manufacturer Cohort 0.63 0.0 Based on 1 male death. PRM based on 0 male deaths among 2,4,5-T exposed workers. Riihimaki et al 1.1 1982 Herbicide Applicators Based on 4 male deaths with ten year latency period. Axelson et al 1980 Railroad Sprayers 2.2 3.1 (6.1*) Based on 3 male deaths. Based on 2 male deaths with only phenoxy acid exposure. (with a ten year latency period) 3.1 (5.6) Based on 1 male death with phenoxy acid and amitrole exposure, (with a ten year latency period) 0.0 Based on 0 male deaths with only amitrole exposure. Ott et al 1980 Manufacturer Cohort 0.0 Based on 0 male death. * = Significant at the p=0.05 level. 2498 i?A5?<V H-133 Human Health HRisk Assessment TOXICITY/ STUDY POINT ESTIMATE OF RELATIVE RISK >1.0 <=1.0 COMMENT LUNG CANCER Cohort Studies- Lynge 1985 Manufacturer Cohort 1.19 2.21 2.06* 1.28 Based on 38 male cases. Based on 6 female cases. Based on 11 male cases in phenoxy acid manufacture and packaging/': Based on 1 female case in phenoxy acid manufacture and packaging. Zack & Gaffey 1983 Manufacturer Cohort 1.41 1.68 Based on 14 male deaths. PRM based on 6 male deaths among-'* 2,4,5-T exposed workers. . Riihimaki et al 1.1 1982 Herbicide Applicators Based on 12 male deaths with ten^ year latency period. Axelson et al 1980 Railroad Sprayers 1.4 Based on 3 male deaths. 0.0 Based on 0 male deaths with only phenoxy acid exposure. 1.9 (2.9) Based on 1 male death with phenoxy acid and amitrole exposure (with a ten year latency period) 3.2 (2 .6) Based on 2 male deaths with only amitrole exposure. (with a ten year latency period) Ott et al 1980 Manufacturer Cohort Based on 1 male death. = Significant at the p=0.05 level. 2499 R.132 4-60- Human Epidemiology TOXICITY/ STUDY POINT ESTIMATE OF RELATIVE RISK >1.0 <=1.0 COMMENT OVERALL CANCERS --------- Cohort Studies------------------------- Lynge 1985 Manufacturer Cohort 1.05 0.99 0.88 0.87 Based on all 159 male cases. Based on all 49 female cases. Based on 28 male cases in phenoxy acid manufacture and packaging. Based on 13 female cases in phenoxy acid manufacture and packaging. Zack & Gaffey 1983 Manufacturer Cohort 1.13 0.82 Based on all 35 male deaths. PRM based on 9 male deaths among 2,4,5-T exposed workers. Riihimaki et al 1982 Herbicide Applicators 0.71 0.82 Based on all 26 male deaths. Based on 20 male deaths with ten year latency period. Axelson et al 1980 Railroad Sprayers 1.4 1.1 (1.9) Based on all 17 male deaths. Based on 6 male deaths with only phenoxy acid exposure. (with a ten year latency period) 2.1 (3.4*) Based on 6 male deaths with phenoxy acid and amitrole exposure. (with a ten year latency period) 1.5 (1.5) Based on 5 male deaths with only amitrole exposure. (with a ten year latency period) Ott et al 1980 Manufacturer Cohort 0.28 Based on the 1 male death. = Significant at the p=0.05 level. D2-53-0t>0( H-131 HHuman Health Risk Assessm ent IV. Presentation of Epidemiology Studies by Type of Cancer .-^r Summaries of all cohort studies and relevant case-control studies are prsented below for several types of cancers. Relative risks (risks compared to general population) are presented when available. Relative risks greater than one represents a risk greater than that expected in the general population. All the cohort studies have been included for each cancer to provide c o m -i^ ^ pleteness. In some cases, several small cohort studies, with little information 7"s\j| on their own, combine to present possible patterns of disease. -; \P ^H -I3 0 s -r i Human Epidemiology Zack & Gaffey 1983 USA Manufacturer Cohort Total observed deaths = 163 884 white male hourly workers at Monsanto in Nitro, West Virginia employed at least one year. Exposure to 2,4,5-T was determined only for de ceased Study reports SMR's for the entire cohort and PMR's for the deceased by exposed and unexposed. Only 58 of the 163 deaths were 2,4,5-T exposed. Riihimaki et al 1982 1,971 male herbicide applicators of four employers Finland with at least two weeks exposure to 2,4-D or 2,4,5-T Herbicide Applicators 75% worked less than eight weeks total. Total observed deaths = 144 Axelson et al 1980 Sweden Railroad Sprayers Total observed deaths = 45 348 RR herbicide sprayers with exposure > 45 days Study reports SMR's for the total cohort and three distinct subgroups: phenoxy acid, amitrole and combined exposure. Ou et al 1980 USA Manufacturer Cohort Total observed deaths = 11 204 male workers at Dow Chemical who worked in a 2,4,5-T area for at least one month -157 worked less than one year. ^ III. Case Control Studies Various case-control studies have been conducted to look at risk factors for specific cancers. All the case control studies reported in this section were specifically concerned about associations between phenoxy acid exposures and the cancer being studied. The case control studies are summarized under the headings of the specific cancers being evaluated. 2502 Q.3.t65 H-129 HHuman Health Risk Assessm ent A 9o H-128 8. Reproductive Effects There are no good epidemiology studies of reproductive outcomes associated with exposure to phenoxy herbicides. Much of the informatTotf2^ ^ ? -comes from studies in Vietnam where research conditions and records are poor. The results of the Vietnamese studies, as well as those of U.S. soldiers? exposed in Vietnam and the few other studies, are generally inconsistent. ' ^ 2 The mixed results of studies on reproductive effects could be cxp ecte^ yF -r ~ these effects are very difficult to study. The possibility of some reproductive effects has been raised and should be of concern. ^ 9. Neurologic Effects r While only two small studies are presented, there are numerous case reports of neurologic effects with 2,4-D exposure. 2,4-D should be considered " a potential human neurotoxin. ll.Tables of Cohort Studies The following five cohort studies look at cancer deaths (or incidence) among groups of workers exposed to phenoxy acids. One also evaluates a group exposed to Amitrole. These studies will be referred to throughout this section ' as they pertain to the specific cancer being evaluated. They are presented hertT^r in more detail. The studies are ordered according to the total number of deaths or cases observed. These studies include fairly small cohorts and some rarer diseases may not be represented in their findings. All the studies except that by Lynge (1985) look only at mortality. Lynge used information on the incidence of cancer in his cohort. COHORT STUDIES Lynge 1985 Denmark Manufacturer Cohort Total observed cancer incidence = 208 among 200 individuals 4,459 workers at two factories in Denmark 3,390 males and 1,069 females 940 worked in mfg & pkg of phenoxy herbicides 1,226 worked in manual service functions 1,667 worked in mfg & pkg of other chemicals Remainder worked office and unspecified jobs 59% males and 50% females worked less than 1 year. Study reports results by department and for the entire cohort. Little TCDD contamination. 2503 9 -> Y _ Human Epidemiology A number of small manufacturer cohorts also reported individual cases. A review by Honchar & Halperin (1981) estimated an excess risk of over 40 fold based upon three cases in four cohorts and compared to national statis tics. Additional case reports claim to have found additional cases who worked in manufacture, some possibly from these four cohorts. A total of seven cases diagnosed by pathologists have been reported. STS is a difficult diagnosis even for pathologists. The National Institute o f Occupational Safety and Health (Fingerhut et al, 1983) reviewed these cases. Two pathologists familiar with STS concurred in the diagnosis in only five cases. In addition to the difficulty of diagnosis, there are problems coding STS on death certificates. The International Code for Diseases (ICD) is site ori ented. Thus, an STS o f the stomach may be coded as a stomach cancer. This may be an explanation o f the increased stomach cancers noted in some o f the cohort studies. Of more immediate concern is that the two Swedish case-control studies i._ ,cted their cases using primarily histopathologic characteristics, and did not limit selection by site. The New Zealand and U.S. studies, identified their cases using the more site specific ICD classification of 171 (malignant neo plasm of connective and other soft tissue). Thus, while all the studies used cancer registries and cases confirmed by pathology examination, the Swedish studies probably included more sites (such as STS o f the stomach). The differences between these studies could well be due to different diagnostic criteria. The problems with both diagnosis and coding of STS mean that compari sons using death certificates must be questioned. Thus, while there is some variability of the data, there are some clear difference in technique which could explain these differences. Both case control and cohort studies in various countries have found associations with STS and phenoxy acid expo sures. We conclude that the possibility o f risk for Hodgkin's disease with exposure to phenoxy herbicides has been raised and should be of concern. 7. Summary of Cancer Associations Suggestions o f association with at least five types o f cancer have been found in the epidemiology literature. Each of the five cancers has had both statistically significant associations in some studies and negative findings in others. While there is no conclusive demonstration of any individual associa tion, the suggestion is that phenoxy herbicides in some way initiate or pro mote cancers, and that this is done at a level of exposure experienced in various work settings. One observational studies on sheep exposed through feed treated with herbicide demonstrated a dose-response relationship with intestinal cancer. 2504 H-127 i HHuman Health Risk Assessm ent r y oH -I2 6 O' 3. Leukemia The association between leukemia and phenoxy herbicide exposure has -. not been explicitly studied. Several o f the cohort studies have reported cases : of leukemia, but no clear pattern emerges. ... _ s-- , 4. Hodgkin's Disease Several case-control studies have looked specifically at the occurrence o f ~ Hodgkin's disease and exposure to phenoxy herbicides. Two studies (Hardell,--Eriksson et al, 1979 and Hardell & Bengtsson, 1983), both done in Sweden on J* separate populations, reported statistically significant five fold risks. A recent study in the U.S. (Hoar, Blair et al, 1986) found no excess risk. The differ ences for this disparity is not clear. The studies all appear to have sufficient quality to be given credibility. Given the variability o f the data, we conclude that the possibility of risk for Hodgkin's disease with exposure to phenoxy herbicides has been raised and should be of concern. 5. Non-Hodgkin's Lymphoma Several case-control studies have looked specifically at the occurrence of Non-Hodgkin's Lymphoma and exposure to phenoxy herbicides. Two studies, one in Sweden (Hardell, Eriksson et al, 1981) and one in the U.S. (Hoar,Blair et al, 1986) reported statistically significant five to six fold risks. A recent study in New Zealand (Pearce, Smith et al, 1986) found a non-significant mild increase of risk around 1.4 fold. The authors o f the New Zealand study felt that their findings were not consistent with the other studies, because their study population was likely to have high exposure. Given the variability o f the data, we conclude that the possibility o f risk for Non-Hodgkin's Lymphoma with exposure to phenoxy herbicides has been raised and should be of concern. 6. Soft Tissue Sarcomas Several case-control studies have looked specifically at the occurrence of Soft Tissue Sarcomas (STS) and exposure to phenoxy herbicides. Two studies (Hardell, Eriksson et al, 1979 and Hardell & Bengtsson, 1983), both done in Sweden on separate populations, reported statistically significant five to seven fold risks. Two recent studies, one in the U.S. (Hoar, Blair et al, 1986) and one in New Zealand (Smith, Pearce et al, 1984) found little or no excess risk. STS, a fairly rare tumor, was seen in four of the five cohort studies. In each case this represented an excess. A statistically significant excess of five fold was reported by Lynge (1985) for workers in the manual services (main tenance) category. 250 Human Epidemiology define an exposed population an look for any disease (in this case any can cers) that might occur more frequently than expected. Case-control studies, on the other hand, define the study population by the type o f disease (cancer) being studied, and then look to see if subjects with this disease had more than expected exposure to the chemical (herbicide) of concern. The five cohort studies look at cancer deaths and incidence among groups o f workers exposed to phenoxy acids. One also evaluates a group exposed to Amitrole. These studies will be referred to repeatedly throughout this section as they may be used to evaluate any number of cancers. They will be pre sented in greater detail at the beginning of the following charts, and will be referenced later simply by the name of the author. The cohort studies are ordered according to the total number o f deaths or cases observed. These studies include fairly small cohorts and some rarer dis eases may not be represented in their findings. All the studies except that by Lynge (1985) look only at mortality. Lynge used information on the incidence o f cancer in his cohort. The other studies will be referred to and described only under the heading o f the cancer being evaluated in the tables below. D. Evaluations of A ssociation The following evaluations are based upon all the studies described above and listed in the table below. Due to the fact that very few of the studies evaluated exposure to 2,4-D or 2,4-DP separately from other associated exposures, the extension of these findings to these herbicides must be done with care. Nevertheless, those studies which specifically looked at 2,4-D exposure did not differ greatly in results from the other studies. There is no evidence here that 2,4-D is any less or more toxic than other phenoxy herbicides. A cautious observer would have to conclude that the evidence is suggestive of some carcinogenic effect. 1. Lung Cancer Based upon fairly small studies, there is a suggestion that exposure to phenoxy acids and/or dioxins may cause lung cancer. One difficulty o f applying these findings to the use o f 2,4-D and 2,4-DP is the question o f the role of the TCDD dioxin. It is very difficult to clearly separate these expo sures. However, the only statistically significant increase in lung cancer was reported by Lynge, a study with only minor exposure to 2,4,5-T and the TCDD dioxin. 2. Stomach Cancer Based upon very small studies, there is a suggestion that exposure to phenoxy acids and/or dioxins may cause stomach cancer. 2506 H-125 Q - a b o 7 H Human Health Risk Assessm ent cL 9 Vo$ H-124 Most of the studies involved mixed exposure to various phenoxy cides, chlorophenols and/or other chemicals. Exposure to TCDD, not ated with 2,4-D or 2,4-DP, is of concern in these studies. However, studies involve only minimal confounding with dioxins. These indudejj following: Lynge (1985): a cohort study o f workers exposed primarily to 2,4-D other phenoxy herbicides not contaminated with TCDD. Eriksson et al (1981): a case control study independently analyzed fori 2,4,5-T exposure. Hoar et al (1987): a case-control study independently analyzed use. In addition, an observational animal study showed positive results whii were unchanged by analysis for herbicides contaminated with TCDD and-,: those not contaminated (Newell et al, 1984). Other studies looked primarily at mixed 2,4-D and 2,4,5-T exposures. These include the Swedish studies (Hardell.1981; Harden & Bengtsson, 1983v Harden et al, 1981; Harden & Sandstrom, 1979), as weU as others (Pearce et- al, 1986; Riihimaki et al, 1982; Smith et al, 1984; Smith et al, 1982; Woods ^ al, 1987; Singer et al, 1982). '` StiU other studies looked primarily at 2,4,5-T exposures (Ott et al, 1 Smith et al, 1982; Suskind & Hertzberg, 1984; Zack and Gaffey, 1983), mixtures of chemicals including phenoxy herbicides (Axelsomet al, 1980X FinaUy, reproductive effects were looked at in several ecological studies (Nelson et al, 1979; Thomas, 1980, Field & Ken\ 1979; Hanify et al, 1981; Balarajan & McDowall, 1983). These studies look at the experience o f a general population over time and area, and compare these results to herbicide use levels over the same time and area. The concern about confounding cannot be overcome in many of these studies. However, 2,4-D and 2,4-DP are contaminated with chlorinated dioxins other than TCDD or may have toxic effects o f their own. The assump* "J tion that all the toxicity of phenoxy heibicides is only associated with TCDD exposure does not necessarily follow, and there is evidence that other dioxins may be important factors (Woods, 1987). To ignore the observed human health effects of this group o f herbicides based upon the assumption that all effects are attributable to TCDD would be overly simplistic and not consistent with a conservative approach to assessing human health. C. Study D escriptions The studies evaluated include five worker cohort studies, a number of casecontrol studies, and a few miscellaneous studies. The worker cohort studies 2507 Human Epidemiology Observational Epidemiology I. Discussion A. Strengths & W eaknesses Almost all the human epidemiology information on health effects o f pesti cides is from observational studies. These studies take real life exposure situ ations for evaluation (such as groups of workers) rather than controlled and deliberate exposures (as in animal experiments). This approach has its strengths and weaknesses. The most important strengths in these studies are as follows. First, actual human, as opposed to animal, health effects are being observed. Second, ex posures levels that actually occur in the environment and workplace are being evaluated, as opposed to the very high exposures used in animal studies. And third, exposures to total commercial products, and not just one active ingredi ent, are evaluated. Thus, the questions about "inerts" are reduced, and the need for extrapolation to a different species at much lower exposure levels are eliminated. On the other hand, humans are much less homogeneous than laboratory animals. They differ greatly both in genetic makeup and life environment The actual exposure being evaluated is often associated with other exposures which can confound the results. Thus, it is very unlikely that a worker using or manufacturing pesticides will come into contact with only one pesticide. One of the major concerns in studies relating to the phenoxy herbicides 2.4- D and 2,4-DP is confounding by other phenoxy herbicides, in particular 2,4,5-T. The latter is contaminated with significant amounts of 2,3,7,8tetrachlorodibenzo-p-dioxin (TCDD), a highly toxic compound. The herbi cides 2,4-D and 2,4,5-T were frequently used together and manufactured at the same facilities. Finally, human studies involve many more subjects, take a long time and can be expensive. Almost all o f the sixteen herbicides under consideration have not been evaluated in exposed human populations. The only herbicide group with considerable information is the phenoxy acid herbicides (including 2.4- D and 2,4-DP). B. The Scope of the Studies The studies presented here all involve phenoxy acid herbicides. One study also looks at workers exposed to amitrole. Only for the phenoxy acid herbi cides have sufficient human studies been identified to make even a tentative evaluation. 2508 V -Ojkoi H-I23 Appendix H Human Health Risk Assessment (Qualitative) Section 6 Data for Evaluation of Human Epidemiology 2509 9 2510 O' Journal o f Rural Studies. V0 | 4. No 3. pp. 23J-24T. IV8X Primed ui Great Britain i|7 j.l _ijifr m S3 m.i - ijuij Pcrgamon Press pic Printed with permission from Journal of Rural Studies, c. Shannon Stokes and Kathy D. Brace, "Agricultural Chemical Use and Cancer Mortality in Selected Rural Counties in the U.S.A.," Copyright, 1988, Pereamon Press pic. Agricultural Chemical use ana Cancer Mortality in Selected Rural Counties in the U.S.A.* C. Shannon Stokest and Kathy D. Bracei *Department of Agricultural Economics and Rural Sociology. The Pennsylvania State University. University Park. PA 16802 and i Department of Behavioral Sciences. York College of Pennsylvania. York. PA 17404. U S.A. Abstract -- The relationship between agricultural chemical use and five maior categories of cancer is examined for a sample of rural U.S. counties. County acreages treated with insecticides, herbicides and fertilizers are the variables of primary analytic interest. Findings suggest that agricultural chemical use is related to county cancer mortality. For three of the five categories of cancer included, agricultural chemical use was the best predictor of cancer mortality. Although limitations common to ecological analyses require caution in interpretinc results, the findings are highly suggestive of the need for additional research on possible links between agricultural chemical use and county cancer mortality. Introduction A recent article in Rural Sociology described ruralurban trends and differentials in cancer mortality for the United States between the early 1950s and 1970s (Greenberg. 1984). Rural areas have traditionallyhad lower total cancer rates and lower rates of most siie-specific cancers. During these two decades, historic rural-urban differences in cancer mortality diminished greatly and the trend toward conver gence occurred among almost every type of cancer and among the most rural counties. Although several possible explanations for this convergence have been advanced. Greenberg (1984. p. 149) notes that describing '. . . what has happened is easier than explaining why it happened'. An explanation of such trends and differentials would likely be ad vanced by additional research on factors influencing cancer mortality within both rural and urban en vironments. The purpose of this study is not to explain the convergence of rural-urban cancer mortality differ entials. but to examine the hypothesized impact of "An earlier version of this paper was presented at the annual meeting of the Rural Sociological Society. Salt Lake City. Utah. 30 August 1986. The authors express their appreciation to Michael K. Miller. William B. Clifford. Kenneth P. Wilkinson. Rex H. Warland. Charles W. Pitts and Daniel T. Lichter for helpful comments on an earlier draft. Interpretations of data and any remaining errors are the sole responsibility of the authors. factors which may account for variation in cancer mortality within the rural sector. Work has begun to focus on the possible effects of agricultural activities, type of farming and the resulting exposure to possible carcinogenic substances as factors in the rural environment (Burmeister. 1983: Clark ei al.. 1982: Blair and Thomas. 1979). One of the obvious exposures connected to rural residence in many localities is agricultural chemical use. The amount of chemicals used m agriculture has increased greatly since the early 1950s. resulting in documented gains to agricultural production (Schaub. 1985). U.S. Department of Agriculture researchers have documented this trend noting, for example, that in 1952. 11% of the corn acreage was treated with herbicides: by 1976. 9(1% of tne corn acreage received treatment and in 19S2. 95% was treated (Eichers ei al.. 19"S: Schaub. 1VS51. Herbi cide use increased from ~0.5 million pounds of active ingredient (a.i.) in 196-* to 4 2 0 .4 million pounds a.i. in 1982 (Schaub. 1985. p. I- ). Similarly, the use of insecticides has expanded substantially. The use of chemicals to control insects and diseases on corn and tobacco acreages grew from 1% and 4 7 0 . respec tively. in 1952. to 38% and 76% in 1976 (Eichers ei al.. 1976. p. 14). Earlier research has described the short range impact of agricultural chemical use on the health of rural populations. The more immediate deleterious effects of improper exposure to agricultural chemi- 239 2511 240 C. Shannon Stokes and kathv D. Brace cals has been well documented (Morgan era/., 1980; Swartz. 1975: West. 1964). Reports have indicated a large number of pesticide-related illnesses in fieldworkers (Swartz. 1975: West. 1964). while individual case studies and medical reports illustrate the some times fatal results of incorrect exposure during application (West. 1964). Recognition of these hazards has resulted in a ban on certain substances, product labelling, licensing of those prepared to apply chemicals and the initiation of training sessions by Cooperative Extension personnel in correct handling and application procedures. Ad ditional studies continue to monitor chemically treated fields to determine acceptable re-entry times for workers (Woodrow et al.. 1977). The more immediate effects of these chemicals clearly indicate a need for precautions in application and exposure, but there have also been concerns about the possible long-range effects of exposure since a number of agricultural chemicals have been classified as carcinogenic (Epstein. 1979). What are the long-range effects of these chemicals on the cancer mortality of rural populations? This paper reports the relationship between agricultural chemi cal use and cancer mortality rates of selected rural counties in the US. Agricultural chemical use is examined within a model of county cancer mortality that includes socioeconomic factors implicated in earlier studies. Prior to the convergence in rural and urban cancer mortality rates, total cancer rates among farm residents have been lower ihan among urban popu lations. and some reduced site-specific rates have also been documented (Correa and Haenszel. 1978: Fasal et al.. 1968: Wan and Wright. 1973). Con versely. some higher site-specific cancer rates have also been observed in farm populations and have persisted after factors such as age. sex. race and socioeconomic status were controlled. Some of these unexpected results revealed increased risks of cer tain site-specific cancers for farm workers, higher than expected rates among farm residents and higher than expected rates in some rural counties and regions. Studies of U.S. farmers and farm workers in Washington. Oregon. Iowa. Nebraska and Texas, have all suggested elevated rates for certain types of cancers (Miiham. 1971. 1976: Burmeister. 1983: Blair and Thomas. 1979: Agu er al.. 1980). Higher than expected mortality rates include leukemia, myeloma, stomach, pancreas and prostatic cancers. Elevated rates of leukemia (Fasal et al.. 1968) and cancers of the central nervous system (Choi et al.. 1970) in farm residents have also been reported. For some farm regions, increased rates of lung cancer (Clark er al., 1977. 1982) and of stomach cancer (Hoover et al.. 1975a.b) have been found. Such findings are not restricted to the United States. Zaldivar and Robinson (1973) found excess stomach cancer rates among Chilean farmers and cue similar findings for rural and farm populations in Iceland. Wales. Mexico and Puerto Rico. In Japan. Hirayatna (1976) classified farming as a high-risk occu pation for stomach cancer and leukemia. Rural areas in Finland exhibit increased rates of lip cancer (Lindqvist. 1979). Bulgarian farmers constitute a disproportionate percentage of bladder cancer patients (Chernozemsky et al.. 1977). and testicular cancer rates reveal a higher incidence in predomi nantly agricultural and rural districts in England. Wales and The Netherlands (Talerman et al.. 1974; Lipworth and Dayan. 1969). Swedish research has also suggested a link between herbicide exposure and soft-tissue sarcoma. Hodgkin's disease and nonHodgkin's lymphoma (Hardell and Sandsirom. 1979. as cited in Hoar et al.. 1986). Connections between these cancer patterns and agricultural chemical use have been suggested in some cases, but have not been adequately tested (Burmeister. 1981: Clark era/.. 1977: Miiham. 1971: Lipworth and Dayan. 1969). Agricultural chemical application on a county level was included in one prostate cancer mortality analysis, but no statisti cally significant relationship was reported (Blair and Fraumeni. 1978). Other studies have inferred re lationships between chemical use and site-specific cancers using crop production patterns as a proxy variable, but little research has attempted to test directly the relationship between use of agricultural chemicals and county cancer mortality (Burmeister et at.. 1981: Clark et al.. 1982). A notable exception is the recent case-control study in Kansas which reported a significant link between herbicide use and non-Hodgkin's lymphoma (Hoar er al.. 1986). Procedures Sample counties To test the possible contribution of agricultural chemical use to cancer mortality rates in rural counties, we attempted to identify a set of rural counties whose populations would likely be exposed to varying amounts and types of chemicals. The criteria utilized were also designed to reduce the effects of other environmental and technological factors. After reviewing a variety of measures of rural counties containing substantial agricultural activities and estimating the correlations among a series of these measures, three criteria were used to identify rural counties to be included. Non-metro- 2512 Chemical Use and Cancer Mortality 241 politan counties which met any one of the following criteria were initially included in the analysis: the number of employed persons working in agriculture was equal to or greater than the mean number for all counties: the county had a mean value or greater for land used in farming'; the county had a mean value or greater for the dollar value of all agricultural products sold. Eliminating counties with incomplete or unmatched data. 1497 non-metropolitan counties met one or more of the criteria and were included among the sample counties. 1 Measurement of variables Data for the study were compiled by the National Cancer Institute from data provided by the National Center for Health Statistics (Mason and McKay. 1975). These data contain information on the total number of cancer deaths and age-adjusted cancer mortality rates by race, sex and site of cancer for each county in the contiguous U.S. over the 20-vear penod. 1950-1969. Such data overcome some of the methodological problems intrinsic to the study of degenerative disease. For example, site-specific mortality rates fluctuate widely over short periods of time, particularly among sparsely populated rural areas in which random fluctuations can appear to represent unusually elevated or depressed rates. Partially to offset this problem. 20-vear age-adjusted mortality rates for 1950 to 1969 were used as dependent variables. The 20-vear mortality rates were further grouped into five major categories of related sites (Table 1) to help compensate for both the small number of cancer deaths and small population bases in many rural counties, and the resulting large standard errors associated with their rates. Grouping site-specific cancers results in the loss of some etiological information because combin ing cancers at related bodily sites may not succeed in grouping causally-related illnesses. Nonetheless, the rate stability problem is partially addressed through such a procedure (Greenberg. 1983: 1984). Further, grouping site-specific cancers does recognize the possibility of different etiologies across the five major categories of cancer employed, a distinction not possible when all cancer deaths are combined. Finally, to compensate further for the very small number of cancer deaths in some counties, only those counties reporting 50 or more deaths from a given type of cancer were included in the final analysis. It should be noted that studies of mortality rates tend to underestimate the disease experience of a population because the actual number of people with the disease at any given time is greater than the number dying from it. This has not been an extensive problem for many cancers (Epstein. 1979; Bush. 1984). particularly in comparison to other causes of death. While declines in some site-specific cancers have occurred, statistical reports of in creased survival rates may reflect earlier diagnosis rather than longer survival after onset of the disease (Bush. 1984). In the absence of incidence data for the time period and units of analysis employed, mortality rates were used. Because sex and race are both recognized factors in cancer etiology, only rates for white males are used in this analysis (Cutler and Young. 1975; Epstein. 1979: Greenberg. 1983: Preston. 1976). The small number of non-whites in most rural counties outside the south precluded their inclusion in this study, and the greater occupational exposure of rural males led to the decision to examine female cancer mortality in a subsequent analysis. T a b le 1. Maior groups of cancer Type of cancer ICD code" Genital Prostate (177): testis (178) Urinary Kidney (180): bladder (181) Lymphatic and hematopoietic Hodgkin's disease (201): lymphosarcoma and reticulosarcoma. otner forms of lymphoma (reticulosis)and mycosis fungoiaes 1200. 202. 205): multipie myeloma (203): leukemia and aleukemia (204) Respiratory Nose, nasal cavities, middle ear and accessory sinuses (160): iarvnx (161): trachea, bronchus and iung specified as primary: and lung bronchus, unspecified as to whether primary or secondary (162.163) Digestive Esophagus (150): stomach (151): large intestine except rectum (153): rectum (154): biliary passages and liver stated as to be primary sue (155): pancreas (157) *Source: World Health Organization (1948) Manual of the International Statistical Classification of Diseases. Injuries, and Causes of Death. 6th edn. Vol. 1. Geneva. Switzerland. 2513 24: C. Shannon Stokes and Kathy D. Brace The dependent variables then represent average annual age-adjusted mortality rates (per 100.000) for the 1950-1969 period (Mason and McKay. 1975). Subsequent work will examine lagged models in which cancer rates are viewed as dependent upon chemical use in earlier periods. However, the latency period for many types of cancer has been estimated at 20-40 years (Greenberg. 1984). Thus, data availability limit efforts to test many lagged models, even if the appropriate time interval were known. For example. Census of Agriculture data on county-level chemical use other than fertilizers are not available before 1964. shortly after the midpoint of the period for which the cancer rates are calculated. While earlier measurements on this crucial independent variable would have been desir able. the present effort represents a preliminary attempt to test the hypothesized link between chemical use and cancer mortality in an ecological model. Moreover, the consistency of county agri cultural production patterns from year to year suggests that these indicators of chemical use would likely be strongly related over time. Data for the central explanatory variables, agricul tural chemical use. were obtained from the 1964 Census of Agriculture. Three categories of chemical use were reported: (1) acres of land treated with dry and liquid fertilizers. (2) acres of crops sprayed for control of insects and diseases (insecticides).2 and (3) acres of crops or land treated during the year for control of weeds, grass, and brush (herbicides) (U.S. Bureau of Census. 1966). The percentages of the total county farmland acreage treated with each type of chemical (fertilizer, insecticide, herbicide) serve as the measures of agricultural chemical use. While it would have been preferable to have direct measures of the amount of each chemical that was used, such data were not available. Similarly, the number of applications to a given plot was not known. Thus, the measures are conservative esti mates of chemical use during the period under study and undoubtedly underestimate the use of these three categories of chemicals. Although we would prefer more detailed and precise information on the types and quantities of agricultural chemicals used, the conservative nature of the chemical use data biases the findings toward null results. While no bias is ideal, a conservative bias is clearly preferable to one biased in favor of the research hypothesis. Although the primary focus of this study is on the influence of agricultural chemical use. other factors have been identified as important in earlier research on cancer. The possible effect of manufacturing industries on cancer rates has been widely noted (e.g. Hoover ei al.. 1975: Greenberg. 1983). To assess the relative contribution of this variable to county cancer mortality, the proportion of each county's total 1960 employed population that was employed in manufacturing was calculated (U.S. Bureau of Census. 1962). Similarly, mining has been identified as a high-risk occupation for certain sitespecific cancers (Hoover et al.. 1975: Page ei ai.. 1976). Census data on the proportion of county employees who in I960 worked in mining industries were also obtained. Environmental contaminants previously identified as contributing to explanations of cancer mortality have often been associated with urban locations (Greenberg. 1983). The selection of non-metro politan counties controlled part of the possible effects of urban residence. To further control the impact of urban influence, a measure of ruralitv was constructed using the size of largest place within the county and adjacency to a metropolitan area. Using 1960 SMSAs. counties were coded from those with most urban influence to those that were most rural. The categories were: (1 ) adjacent to a metropolitan county and with an urban place of 10.000 or more. (2) adjacent and with an urban place of 2500-9999. (3) adjacent but entirely rural. (4) non-adjacent but with a place of 10.000 or more. (5) non-adjacent with an urban place of 2500-9999. and (6) nonadjacent and entirely rural. Other variables frequently included in studies of cancer mortality include socioeconomic status and ethnicity. Socioeconomic status has been identified repeatedly as an important factor in individual-level analyses (Correa and Haenszel. 1978: Cutler and Young. 1975: Graham. 1969: Kitagawa. 1977). A variety of measures of this variable have been used, including occupation, education, and income, as well as indices devised from these charactenstics. The potential influence of occupation was included as a risk factor represented oy the manufacturing and mining variables The impacts of education and income were measured through two separate indi cators. Census data on males' median educational levels and median family income (1960) were selected as indicators of county-level socioeconomic status. Finally, several studies have found ethnic back ground to be associated with certain site-specific cancer rates (Graham. 1969: Hoover et al.. 1975b). Consequently, the proportion of the total county population that was foreign stock was included. Foreign stock refers to the proportion of the population that is foreign-born plus those who are native-born of foreign parentage. Multiple regression models are estimated separately for each of the five categories of cancer included. Chemical Use and Cancer Mortality 243 Ordinary least squares equations are estimated using a linear specification in the absence of more com plete information as to expected functional form. The models estimated in Table 2 support the decision to examine separately cancer deaths at related sites. With the exception of the mining and rurality variables that are positively related to cancer mortality in each case where they are statistically significant, the remaining variables reveal contrast ing signs, depending upon the cancer site being examined. Among the agricultural chemical variables, the percentage of farmland treated with herbicides is the most consistently related to cancer mortality. In four of the five models, herbicide use is significantly related to cancer rates. The standardized partial regression coefficients indicate that herbicide use is the strongest predictor in the genital and lymphatic cancer regressions and the second best predictor in the digestive cancer equation. Herbicide use is positively and significantly related to each of these categories of cancer. Surprisingly, herbicide use is also significantly related to respiratory cancer, but in a negative direction, a finding for which we have no ready explanation. It is interesting to note, however, that in the one equation where this reversal of expected sign occurs, the coefficient for insecticide use is large and positive. Insecticide use is not only significantly and positively related to respiratory cancer (Beta = 0.46). it is the best predictor of this type of cancer of the nine variables considered. Use of insecticides is unrelated to urinary, lymphatic or digestive cancers. Genital cancer mortality is negatively related to insecticide use. contrary to expectations. Similar to the respira tory equation in which the anomalous negative effect of one chemical occurred in the presence of a strong positive impact of another, herbicide use emerges as the strongest predictor of genital cancer (Beta = 0.32). Whether these two findings reflect a particular combination of agricultural practices, types of farm ing. soil types, or other exposures which may be related to elevated rates of genital or respiratory cancer could not be ascertained. Given the modest correlation between insecticide and herbicide use (0.3). this finding does not appear to be a statistical artifact of collinearity.'' As a further check on these unanticipated findings, particularly the negative sign for herbicides in the respiratory cancer equation and the negative impact of insecticides in the genital cancer equation, two additional analyses were run (data not shown). First, the limitation to counties reporting 50 or more deaths was dropped and the models were reesti mated on the approximately 1500 counties included in the original sample. Secondly, in an attempt to ascertain whether similar results would obtain within more homogeneous agricultural regions, separate models were also estimated for all counties in seven mid-west states in which com and soybeans pre dominate and where similar chemical use patterns might be expected.4 The findings were consistent with those reported in Table 2. The unexpected signs of the coefficients in the genital and respiratory equations remained the same for the entire sample of counties and for the midwest subsample, although the magnitude of coefficients and levels of significance varied. The consistency of these findings across the different sample configurations suggest that these results are not merely a function of the counties included nor the decision rules employed. Fertilizer use was largely unrelated to cancer mor tality. It failed to exert a significant impact in four of the five regressions, and in the one case where it was statistically significant (digestive cancer), it was negatively related and of marginal size (Beta = -0.09). Manufacturing employment is significantly related in the digestive cancer equation, indicating that an increase in the percentage of the labor force in manufacturing is positively related to this cause of death. It is unrelated in any other regression, perhaps reflecting the small proportion of the labor force employed in manufacturing in this sample of rural counties. Mining, by contrast, was positively related to genital, respiratory and digestive cancer. Its largest impact, as expected, was on respiratory cancer. Notably, however, the impact of mining (Beta = 0.11) in the respiratory equation was only about one-fourth that of insecticide use (Beta = 0.46). The rurality measure was positively related to urinary and lymphatic cancer rates, but not signifi cantly related to the more frequently occurring cancers. The coefficients for income and education are significant in both the respiratory and digestive equations. In each case, their impact is of opposite sign. Education is negatively related to respiratory and digestive cancer, while income exerts a positive influence. Conversely, income reveals a negative coefficient for genital cancer, while education is positively related to lymphatic cancer. Neither vari able is significant in the urinary cancer re gression. 2515 > S K p IC p - SJ C. Shannon Stolces and Kathy D. Brace ~ M 02 V pv P Table 2. Sum m ary of O l.S regressions o f counly -- while male cancer m ortality rales for specific types of cancer on agricultural chemical use and selected ecological variables* Variable Insecticide H erbicide Fertilizer M anufacturing M ining Ruralily M ediatt family income M edian educational level Foreign slock Adjusted K l F-ratio G enital bP --1 129* 12.630 -1286 0 639 10 2951 0 102 - 0 (KM 0 255 7 968 119 8.348 - 0.186 0 320 - 0 057 0.024 0.091 0.051 - 0 237 0.098 0.227 U rin ary bP -3.490 -0315 2.406 1.080 -6.533 0 314 0 001 0 318 6.612 0 156 4.055 0 109 0012 0 169 0 066 0.052 0 225 0.174 0 150 0.275 Lymphatic bP Respiratory bP --4.646 7.009 -0.529 -1.507 -1 640 0 223t -0.000 0 299 1.308 0078 4.558 -0.117 0 221 -0.030 -0.072 -0018 0 134 - 0 046 0 149 0.046 57.488 - 1 9 151 -4.298 -5.635 23.610 0.105 0 002 -0.168 -28.861 0 229 24.993 0 455 - 0 178 - 0 072 - 0 075 0.108 0020 0.283 - 0 185 0.298 Digest ive bp 3.463 21.529* -5.405 8.690 12.330 0 140 0 001 -0.719 42.850 0.363 67.673* 0.026 0 216 -0092 0 119 0 054 0029 0.173 - 0 III) 0 491) *For counties with at least SO d eath s due to specified type of cancer M ean cancer m ortality rates and nutulrct of counties ittclttded are: genital cancer (10.7. = 489). urinary cancer (11.0, = ISO), lymphatic cancer (IR. I , = 381). respiratory cancer (.13.7, = 727) attd digestive cancer (>18.7, = I05S). t/P>===S0IM.0M5.. Chemical Use and Cancer Mortality 245 The coefficients for the percentage of the population classified as foreign stock are substantial and signifi cant in four of the five equations. The impact is particularly noticeable for digestive cancer where foreign stock is the strongest predictor in the equation (Beta = 0.49) and where the best fitting model is found (R2 = 0.36). This finding again confirms the likely influence of ethnicity on digestive cancer (Hoover et al.. 1975). Foreign stock is also significant in the genital, urinary and respiratory regressions. The moderately strong negative co efficient in the respiratory regression contrasts with the positive signs in the other models, again support ing the decision not to examine total cancer mor tality rates, but rather to group cancers at related sites. Whether the negative impact of foreign stock on respiratory cancer reflects different patterns of cigarette consumption or other factors cannot *be determined from these data, but the findings are suggestive of delimited areas for further research. Discussion Significant associations were found between agricul tural chemical use and four of the five categories of cancer examined. For three of the five models, agricultural chemical use was the best predictor of cancer mortality. Herbicides were positively and significantly associated with genital, lymphatic and digestive cancer. Insecticides had a strong positive relationship to. respiratory cancer. In two instances, insecticides in the genital cancer regression and herbicides in the respiratory regression, signs of the coefficients were contrary to expectations. In each of these anomalous cases, a much stronger and positive relationship was exhibited with the other major pesticide. Fertilizer use was largely unrelated to cancer mortality with the exception of a modest negative association with digestive cancer. Of the remaining social, economic and demographic variables, foreign stock exhibited the largest and most consistent influence. Foreign stock was the strongest predictor of digestive cancer, suggesting that ethnicity was positively related to this cause of death. Similarly, foreign stock exhibited positive impacts on genital and urinary cancer, but negative effects on respiratory cancer. Income and education were both significant in respiratory and digestive cancer, but of opposite sign. As expected, mining was important to respira tory cancer, but it also was positively related to genital and digestive cancer. Manufacturing employ ment was significant in one instance (digestive cancer), while ruralitv exhibited positive effects on urinary and lymphatic cancer. Although mixed, the findings are highly suggestive of the need for additional research on possible links between agricultural chemical use and county cancer mortality. However, several limitations of the study must be recognized. Common to ecological studies, direct links between persons exposed to agricultural chemicals and those who died of cancer cannot be made. Thus, as Clark et al. (1982) note, those who died may not have been involved in farming. Conversely, there are multiple pathways through which chemicals are dispersed in the environment and farm workers are clearly not the only persons exposed to potential risks (Glotfelty. 1985: Severn. 1985: Sieber. 1985). Nonetheless, caution must be exened in interpreting these results. A second problem relates to the appropriate time referent for the cancer rates given the long latency periods for many types of cancer. If a 20+ year latency period characterizes the cancer rates examined here, then this analysis may well under estimate the influence of agricultural chemicals. Clark et al. (1982. p. 4) used a 20-vear lag because they `. . . thought that . . . was the only time period for which an association with the use of OC (organochlorine) pesticide could be observed'. Our results indicate that significant associations may be found within shorter time periods. As data for the 1980-1985 period become available, more appro priately lagged models can be estimated. In the interim, we are currently attempting to estimate lagged models for the 1975-1980 period. An additional problem of the study is the lack of detailed data on the types, quantities and frequency of chemical applications, as well as behavioral practices in their application, e.g. use of masks, aerial spraying, etc. In the absence of such data, some investigations have used the proportion of harvested land in a given crop as a surrogate measure of the intensity of chemical use (Clark et al.. 1982). Such procedures are several steps re moved from the indicators necessary to measure exposure more directly. The measures of agricul tural chemical use in this study, percentages of total farmland acreage treated with insecticides, herbi cides or fertilizers, are subject to similar problems. Census of Agriculture data on county-level chemical use are extremely limited and. as noted, may bias findings toward null results. The finding of signifi cant relationships where the epistemic correlations between concepts and measures are likely to be modest encourages further work. In that regard, the consistency between our findings and those of Clark et al. (1982) indicate that observed relationships are not likely to be simply artifacts of the methods employed. 2517 Q. 246 C. Shannon Stokes and K.athv D. Brace Finally, county-level behavioral data on lifestyle factors such as diet, smoking or alcohol consumption are not available for this period. Such factors could possibly confound some of the associations observed in this study. Controls for foreign stock, rurality and socioeconomic status of the population partially address this issue. Moreover, some have argued that similar patterns of alcohol consumption, cigarette smoking and nutrition now characterize both rural and urban America (Greenberg. 1984). Nonethe less. lifestyle differences may remain which are not accounted for in these ecological models. Unless one posits systematic relationships between such lifestvie factors and the variables of primary analytic interest to this study, relationships to our knowledge not yet examined empirically, lifestvie differences remain a possible alternative explanation of indeterminant plausibility. The contribution of agricultural chemicals to farm production is well established (Schaub. 1985). With one estimate of pre- and postharvest commodity losses caused by insects in the United States in 1981 over 20 billion dollars (Klassen and Schwartz. 1985. p. 280). their use is likely to continue. While evaluations of the toxiciry and possible carcino genicity of the substances involved is the proper purview of biological and medical researchers (Epstein. 1977), ecological studies involving demographic, socioeconomic and agricultural factors can and should be monitored by social scientists. Environmental sociologists, demogra phers. geographers and rural sociologists would ail appear to have a role to piav. Notes 1. This procedure produced a much larger number of counties than would have resulted if a more restncted definition of agriculturally-based employment activities had been used fBrown and Beale. 1981). For example, restricting the sample to only those counties with 20 or 25% of the total employed population in agriculture would have identified counties in which agriculture was a dominant industry, but it would also have signifi cantly reduced the sample size. Moreover, farm workers and those in agriculturally-related industnes are not the only persons exposed to agricultural chemicals in the rural environment. Thus, the more inclusive approach was deemed more appropriate to this exploratory effort. 2. Although we use the term insecticides to refer to this category of chemicals, a number of other pesticides are also included. 3. In addition to the modest correlation between these two variables, the SAS collineanty diagnostic pro cedures revealed no collineanty problems involving the chemical variables. Other than the expected correlation between income and education, there was little evi dence of harmful or degrading collineanty in the data matrix. 4. The seven states were Ohio. Indiana. Illinois. Iowa. Minnesota. Michigan and Wisconsin. Counties with 50 or more deaths were included in order to increase the stability of rates within the region. References Agu. V.L'.. Christensen. B.L. and Buffler. P.A. (1980) Geographic patterns cf multiple myeloma: racial and industnal correlates, state of Texas. 196Si--1971. Journal of the national Cancer Institute 65. 735-738. Blair. A. and Fraumeni. J.F.. Jr (1978) Geographic patterns of prostate cancer in the United States. Journal of the National Cancer Institute 61. 1379-1384. Blair. A. and Thomas. T.I. (1979) Leukemia among Nebraska farmers: a death certificate study. 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In A g ric u ltu ra l C h em icals o f the F uture, pp. 15-26. Hilton. J.L. (ed.). Rowman Allanheld. Totowa. NJ. Severn. D.J. (1985) Involuntary exposure to pesticides from agricultural use. In A g ric u ltu ra l C h e m ica ls o f the F uture, pp. 403-409. Hilton. J.L. (ed.). Rowman it Allanheld. Totowa. NJ. Sieber. J.N. (1985) General principles governing the fate of chemicals in the environment. In A g ricu ltu ra l C h e m i cals o f th e F uture, pp. 389-402. Hilton. J.L. (ed.). Rowman & Allanheld. Totowa. NJ. Swartz. J. (1975) Poisoning farmworkers. E n v ir o n m e n t 17. 26-33. Talerman. A.. Kaalen. J.G.A.H. and Fokkens. W. (1974) Rural preponderance of testicular neoplasms. B ritish J o u r n a l o f C ancer 29. 176-178. United States Bureau of the Census (1962) U n ited States C e n su s o f P o p u la tio n : 960. U.S. Government Printing Office. Washington. DC. United States Bureau of the Census (1966) C ensus o f A g ricu ltu re : 1964. U.S. Government Printing Office. Washington. DC. Wan. T.T.H. and Wnght. A. (1973) Occupational differ entials in chronic disabilities. J o u r n a l o f O ccu p a tio n a l M ed icin e 15. 495-498. West. I. (1964) Occupational diseases of farm workers. A r c h iv e s o f E n v ir o n m e n ta l H e a lth 9. 92-98. Woodrow. J.E.. Seiber. J.N.. Crosby. D.G.. Moilanen. K.W.. Soderquist. C.J. and Mourer. C. (1977) Airborne and surface residues of parathion and its conversion products in a treated plum orchard environment A rchives o f E nvironm ental C ontam ination and T oxi c o lo g y 6. 175-191. World Health Organization 11948) M a n u a l o f m e In te r national Statistical Classification o f Diseases. Intim es, a n d C auses o f D eath. Sixth Revision of tne International List of Diseases and Causes of Death. Voi. I Geneva. Switzerland. Zaidivar. R. and Robinson. H. (1973) Epidemiological investigation of stomach cancer mortality in Chileans: association with nitrate fertilizer. Z e its c h r ift fu r K rebsfo r s c h u n g 80. 289-295. 2519 o -30*0-0 J \x*>X-0 02SS GENETIC TOXICOLOGY An Agricultural Perspective Edited by RAYMOND A. FLECK UniversityofCalifornia. Davis Davis. California ALEXANDER HOLLAENDER Associated Universities. Inc Washington. D.C 2521 O* 9^3-2- STUDY OF PESTICIDE GENOTOXICITY M ichael D. W a te rs ,1 Shahbeg S. S andhu,1 Vincent F. Simoon,2 K ristie n E. M ortelmans,2 Ann D. M itc h e ll,2 Ted A. J o rg e n s o n ,2 David C Ruby V a le n c ia ,3 and N eil E. G a r r e tt4 1G enetic T oxicology D iv isio n U.S. Environm ental P ro te c tio n Agency R esearch T ria n g le P ark , NC 2SRI I n te r n a tio n a l Menlo P ark, CA 3WARF I n s t i t u t e , In c . Madison, WI 4N orthrop S e rv ic e s , In c. R esearch T ria n g le P ark , NC INTRODUCTION With a lim ite d supply o f a ra b le land su p p o rtin g an e v e rin c re a s in g human p o p u la tio n , th e t h r e a t o f crop lo s s to a g r i c u lt u r a l p e s ts becomes c o n tin u a lly more a c u te , Thus p e s ti c id e s have become an e s s e n t i a l component o f modem a g r i c u lt u r e . As competing organism s evolve r e s is ta n c e to commonly used a g e n ts , new and more e f f e c ti v e p o iso n s and r e p e l la n t s must c o n s ta n tly be developed. The fundamental problem in p e s tic id e development i s to produce chemicals th a t a c t s p e c ific a lly ag ain st c e rta in organisms w ithout adversely a ffe c tin g o th ers. Because of the s im ila r itie s in th e s tr u c tu r a l, m etabolic and g en e tic components o f a l l l i f e forms, absolute species s p e c ific ity is frequently d if f ic u lt to a t t a i n . F u rth erm o re, such to x ic chem icals im properly used may engender b io lo g ic a l e ffe c ts beyond those fo r which they were o rig in a lly manufactured. 275 280 MICHAEL D. WATERS ET A L T able 2 . G en o to x icity B ioassays Employed D escriptor Organism P ro p erty Examined Reference Point/Gene M utations in Prokaryotes SAL* S. typhim urium (5 s t r a i n s ) WPU* E. c o l i WP2 uvrA Point/Gene M utations in Eukaryotes YER S. c e r e v is ia e D7 L5T Mouse lymphoma L5178Y c e l l s SRI D. m elanogaster Prim ary DNA Damage in P rokaryotes REP* E. c o li polA REV* B. s u b t i l i s ree SAR S. typhimurium uvrB, ree Prim ary DNA Damage in Eukaryotes YE3* S. c e r e v is ia e D3 YEH S. c e r e v is ia e D7 UDH* Human lung f i b r o b l a s t s WI-38 Chromosomal E ffe c ts see Chinese hamster ovary c e lls MNM Mouse bone marrow and cardiac blood DIM Mouse Reverse m utation Reverse m utation Reverse m utation Forward m utation R ecessiv e leth ality D ifferential to x ic ity D ifferential to x ic ity D ifferential to x ic ity Enhanced m ito tic recom bination Gene c o n v ersio n and crossing-over Unscheduled DNA synthesis Sister-chrom atid exchange Chromosome breakage (m icronuclei) Dominant leth ality a) - (2) C27) . (5) ,, (25) (21) (13) (1) (4) (28) , (19) (16, 22) (i7) : (18) 25CG 9 - / I*A b io assay from Che i n i t i a l b a tte ry of screening t e s t s . ichlorfon Ni *'T NT -.f rr mt3t Compound Brornaci1 Point/Gene Mutation __________ DNA Damage__________ Chromosomal Prokaryote Eukaryote Prokaryote Eukaryote E ffe c ts SAL WPU YER L5T SRI. REP REW SAR YE3 YEN UDH SCC MNM DLM _____________________________________ ____ -- ----------- Cacodylic acid D iallate Dicamba Dinoseb DSMA Honuron +* + USUA Pentachlorophenol Propanil Siduron Simazine S ulfallate +* T riallate +* T rifluralin 2 , A-D 2.A-DB 2, A,5-T or _!------------------ro o V c V vs\ t ? v r c rr CIZ.T C c r aKtf 1SET, ted J MLDY OF PESTICIDE GENOTOXICIT Y o. . f Prim ary DHA Damage. A lthough 29 o f th e 35 p o s itiv e p e s tic id e s T caused prim ary DNA damage o n ly 16 caused prim ary DNA damage b u t not p o in t/g e n e m u ta tio n . A unique group of 10 p e s tic id e s was found t h a t caused DNA damage o n ly i n p ro k a ry o tic system s (T able 11); however, te s t in g f o r gene m u ta tio n and chromosomal damage by th e s e compounds i s n o t com plete. A la r g e number o f th ese compounds a re c h lo rin ated arom atics (F igure 10). The halophenoxy h e rb ic id e s 2,4-D, 2,4-DB and 2 ,4 ,5 -T (F ig u re 11) form a subgroup of c h lo rin a te d compounds; evidence of p o s itiv e e u k a ry o tic a c tiv ity fo r the phenoxy cg h e rb ic id e s has been p re s e n te d e lsew h ere (2 6 ). Although te s tin g is incom plete, m -dichlorobenzene and pentachlorophenol were p o s it i v e o n ly f o r DNA damage in a p ro k a ry o tic and a e u k ary o tic system , and fo u r p e s tic id e s (e th y l chrysanthem ate, mancozeb, maneb, and z in e b ) were p o s it i v e only fo r DNA damage in eukaryotic systems (Table 12). The l a s t th re e chem icals in th is group have s im ila r s tru c tu re s (F igure 12) and are c la s s if ie d as ethylenebisdithiocarbam ate fungicides. Since the data in Tables 7 and 8 suggest th a t th e p o s itiv e r e s u l ts o b tain ed in th e S. c e re v is ia e D3 assay (YE3) may be confirm ed in th e L5T system , th e fiv e chem icals in Table 12 should be e v a lu a te d f u r t h e r f o r gene m utatio n in eukaryotes. Chromosomal Damage. A lthough th e i n i t i a l t e s t b a tte r y did not include t e s t s fo r chromosomal damage, nine p e s tic id e s (Tables 7 and 8) were observed to d is p la y t h i s e f f e c t . E ig h t of th ese chemicals caused a p o sitiv e response fo r sister-ch ro m atid exchange in CHO c e l l s (SCC) b u t o n ly t h r e e , c a c o d y lic a c id , monuron, and *1 benomyl, caused m ic ro n u c le i fo rm a tio n in d ev eloping e ry th ro c y te s m of th e mouse (MNM). Each o f th e s e compounds a ls o caused p o in t/g e n e m utations or DNA damage, o r b o th . The a c tiv e gene m utagens, acephate, demeton, monocrotophos, and tric h lo rfo n , were p o sitiv e in e u k a ry o tic gene m u ta tio n and p rim ary DNA damage a ssa y system s except SRL. The f iv e o th e r compounds, d i s u lf o to n , m e th y l-p a ra th io n , cacodylic a c id , monuron, and benomyl, were p o s itiv e in eukaryotic gene o r DNA damage a ssa y s b u t were n e g a tiv e (o r were n o t te s te d ) in th e p ro k a ry o tic p o in t/g e n e a s s a y s . A ll nine o f th e s e chromosome damaging compounds were p o s it i v e in th e L5T system . N egative r e s u l ts were o b ta in e d f o r te n p e s ti c id e s e v a lu a te d in th e mouse dominant le th a l t e s t . S ix of th e s e compounds were p o s itiv e in a t l e a s t two e u k a ry o tic a s s a y s . The s i x a re th e i n s e c t ic id e s azin p h o sm ethyl, m ethyl-parathion, and monocrotophos, the h erb icid e brom acil, and th e fu n g icid es captan and f o lp e t. Comparison o f B ioassay and C arc in o g e n ic ity Data A comparison of th e g en o to x ic ity t e s t r e s u lts w ith carcin o g e n ic ity s tu d ie s o f 15 p e s ti c id e s i s shown in T able 13. Four h erb ic id e s ( d i a l l a t e , monuron, s u l f a l l a t e , and t r i f l u r a l i n ) and one fungicide (captan) evalu ated in th e p rese n t study cause tumors in 2525 9 - / j / T able 11. P e s tic id e s P o s itiv e only f o r DNA Damage in P ro k a ry o tic Systems u KJ Compound Point/Gene M utation Prokaryote Eukaryote SAL WPU YER L5T SRL __________ DNA Damage_________ Prokaryote Eukaryote REP REW SAR YE3 YEH UDH Chlorpyrifos (I) - Chrysanthemic acid (I) - o-dichlorobenzene (I) - 2,4-D (H) - 2,4-DB (H) - Dicamba (H) - Dinoseb (N) - P ro p a n il (H) ttooOJT 2,4,5-T (H) - cn> sec-butylam ine (F) - - +++ - -+ - -- -t - - +- - - - ++- - - +++ - - ++ - -+ - +- - - - MICHAEL D. WATERS ET AI 3 1 4 MICHAEL D. WATERS ET Al 2,4-DB Acid REP ci / \ Cl 2,4, 5-T ci Cl. n \ 0-- CNj----- C -- OH CI Fig. 11. REW T h ree phenoxy h e rb ic id e s t h a t e l i c i t e d p ro k a ry o tic DNA damage. 2527 9 - / 3 3 frtM MICHAEL D. W ATERS ET t Table 13. Comparison o f G enotoxicity and C arcin o g en icity T est f'H R esults P e stic id e s G enotoxicity C arcinogenicity ' M P ositive C arcinogenicity Captan (F) +: SAL, WPU, L5T, SRI, REP, REW, SAR, YE3 UDH, DIM D ia lla te (H) +: SAL, L5T, SRL, YE3 WPU, YER, YEH Monuron (H) +: L5T, SCC, MHM 9 tests S u l f a l la t e (H) (m utagenicity te stin g incom plete) + : SAL 4 tests T r i f l u r a l i n (H) 7 tests Mice m/f +/ Rats m/f Ref. (9) * H /+ / u + + d i) +/+ +/+ (9) -/+ (9) Possible C arcinogenicity Azinphos-methyl (I) +: L5T, YE3 10 t e s t s Fenthion (I) 5 tests Paratbion (I) 8 tests / /t/t (9) (9) (9) Negative C arcinogenicity Diazinon (1) 4 tests Endrin (I) -: 6 tests M alathion (1) -: 8 tests Methoxychlor ( I) 5 tests M ethyl-parathion (I) +: L5T, YE3, SCC 8 tests PCNB (F) ` v ; 6 tests" 2,4-D and e s t e r s (H) +: REV, REP 5 tests (9) (9) (9) (9) (9) (9) * (12) + = p o sitiv e response, = equivocal, " = negative response (under conditions o f'b io assay ; not n ecessarily non-carcinogenic). 2528 2529 f / & I2tg particularly on smaller farms where the farmer is more likely to have personally engaged in herbicide application. This expo sure-response gradient persisted despite study limitations in Herbicides and Non-Hodgkin's exposure assessment that would tend to mute any exposure-re-' sponse effect. For example, acres sprayed is only a surrogate Lymphoma: New Evidence measure for delivered dose--a farmer's use of herbicides in 1970 may not be representative of use in other years, and a large From a Study of Saskatchewan proportion of subjects are likely to have ceased farming since 1970. Farmers Third, the exposure information available in this cohort, although less thanthat available in case-control studies, would be less affected by accuracy of respondent recall, a major criticism Aaron Blair of case-control studies. In the cohort study presented here, the information on herbicide use in 1970 is probably reasonably accurate, but it is unclear how well herbicide use during this year represents farmers' use inother years. The results from the cohort The lifestyle of farmers is usually perceived as healthy because study are also unlikely to be due to case-response bias, an issue it includes hard work, clean air, fresh food, and avoidance (at often raised in regard to case-control studies. When based on least to some degree) of unhealthy habits such as tobacco and analysis of deaths that occurred after 1981, the association alcohol use. The epidemiologic literature supports this perception between the use of herbicides and the risk of non-Hodgkin's and has consistently shown that farmers have a more favorable lymphoma among farmers persisted for years after the determina mortality experience than the general population (7). Despite a tion of exposure in 1970. This minimizes the possibility that the lower mortality from all combined causes and from most major results are due to response bias among non-Hodgkin's lymphoma causes of death, farmers may experience elevated risks forcertain 'cases.' .. -cancers, particularly cancers of the stomach, connective tissue, -- Finally, die association was specific. Among these farmers, an skin, brain, prostate, and lymphatic and hematopoietic system. association with herbicide use. was limited to non-Hodgkin's 'Although some investigators disagree whether the factors in the ________ andjcould not be explained by education, income, agricultural environment may account tor these excesses 'ethnicityi expenditures on fuel, or use of fertilizers or insecti potential exposures to herbicides have received considerable cides. attention (3 -8 ), particularly in regard to lymphoma and soft- Wigle et al. (9), through prudent use of readily available data tissue sarcoma.- ------ 7 : Vresources, have provided new information that supports the Inthis issue of the Journal, Wigle et al. (9) present results from hypothesis that contact with herbicides increases the risk of a mortality study of 69,513 Saskatchewan farmers, age 35 years non-Hodgkin's lymphoma among farmers. Case-control studies orolder, which provide further evidence that the use of herbicides have observed non-Hodgkin's lymphoma associated with phe- is associated with the risk of non-Hodgkin's lymphoma. Mortal noxyacetic acid herbicides (3 -7 ) and, in particular, the phenoxy- ity among Saskatchewan farmers was considerably lower than acetic acids 2,4-D (3,4). This study did not contain information that of the general population: -Deficits were also ubsei ved~for on the specifichcrbicides used by the study subjects; therefore, it diseases of ihe circulatory-system, all malignant neoplasms, wasimpossible t&directly evaluate risks associated withpotential accidents, poisoning, and violence. Although no cancer showed a exposure to specific chemicals. The authors note, however, that statistically significant excess among farmers overall, Poisson the phcnoxyacetic acid herbicide 2,4-D accounted for 75%of the "regression modeling indicated that acres sprayed with herbicides weight of all herbicide-active ingredients used agriculturally in and expenditures on fuel in 1970 were independently associated Saskatchewan in 1970 and a greater percentage in 1960. with non-Hodgkin's lymphoma. Further, relative risks rose to Excesses of non-Hodgkin's lymphoma have been reported over twofold among those farmers who spent $900 or more on among farmers in various countries (1). The epidemiologic fuel or among those farmers who sprayed 250 or more acres, e.g., evidence points toward involvement of phenoxyacetic acid her among farmers with operations of less than 1,000 acres. These bicides and, in particular, 2,4-D, but there are inconsistencies. excesses could not be explained by education, income, ethnic The experimental evidence is unimpressive. The International background, production of specific crops, or use of fertilizers or Agency for Research on Cancer concluded that the evidence for insecticides. carcinogenicity of 2,4-D and 2,4,5-T in animals is inadequate This investigation makes a substantial contribution to the (10). This presents a dilemma to the scientific community in how understanding of cancer mortality patterns and various agricul to draw conclusions regarding carcinogenicity of a substance tural practices for several reasons. First, the association between when the epidemiologic and experimental data do not agree, the use of herbicides and the risk of non-Hodgkin'sJymphoma especially in situations where the epidemiologic evidence is :among:Jannax^en in.riris.cohort .study, relianceon --fositiv^and experimental evidence is not. relatively crude census and mortality data, is consistent with findings from most (3 -7 ), but not all (8), case-control studies designed to investigate this issue. Second, mortality from non-Hodgkin's lymphoma rose signif icantly with increasing number of acres sprayed with herbicides, Received February 27,1990; accepted February 28,1990. Occupational Studies Section, National Cancer Institute, Executive Plaza North, Rm. 418, Betfaesda, MD 20892. 544 Journal o f the National Cancer Institute 2% 2T r Ai our research focus in carcinogenesis turns from substances that (lamage the DNA to those that may operate through epige netic mechanisms, perhaps we should anticipate more and more situations as with phenoxyacetic acid herbicides that show exper imental and epidemiologic inconsistencies. The challenge in the future will be to design studies in the laboratory that mimic the human condition and to incorporate biochemical procedures into epidemiologic studies to obtain information on mechanisms. Experimental investigations of pesticides should utilize dermal exposure, the principal route of occupational exposure in hu mans. Although epidemiologic studies that incorporate biochem ical measures are needed to improve assessment of exposure, the study by Wigle et al. (9) demonstrates that traditional approaches linking data collected for other purposes can be valuable, partic ularly when they include some surrogate for dose. References ( /) Blab A, M alker H, Cantor KP, eta l: Cancer among farmers: A review. Scand J Work Environ Health 11:397-407,1985 (2) Bono GG, Boone KM, Cook RR: Phenoxy herbicides and cancer Insufficient epidemiologic evidence for a TM u i relationship. Fundam Appl Toxicol 12:172-188,1989 (3) Hardell L, Eriksson M, Lo w er P, et a u Malignant lymphoma and exposure to chemicals especially organic solvents, cfalorophenols, and phenoxy acids: A case-control study. Br J Cancer 43:169-176,1981 (d) Hoar SK, Blair A, Holmes FF, et al: Agricultural herbicide use and risk of lymphoma and soft-tissue sarcoma. JAMA 256:1141-1147,1986 (5) W oods JS, Poussar L , Severson RK, et al: Soft tissue sarcoma and non-Hodgkin's lymphoma in relation to phenoxyberbicide and chlorinated phenoi exposure in western Washington. JNCI 78:899-910,1987 (6) Persson B, Dahlander A, Fredrdcsson M, et al: Malignant lymphomas and occupational exposures. BrJlnd Med 46:516-520,1989 . (7) L a Vecchia C, Negri E, D 'A vanzo B, et al: Occupations and lymphoid neoplasms. Br J Cancer 60:385-388,1989 (8) Pearce NE, Sheppard RA, Smith AH, et al: Non-Hodgkin's lymphoma and fanning: An expanded case-control study. Int J rnrw 39:155-161. 1987 (9) W igle DT, Semenctw RM, W ilkins K, eta l: Mortality study of Canadian male farm operators: Noo-Hodgkin's lymphoma mortality and agricultural practices in Saskatchewan. J Natl Cancer Inst 82:575-582,1990 (10) International Agency for Research on Cancer: Evaluation of carcino genic risks to humans. Overall evaluations of carcinogenicity: An update. IARC Monogr Eval Carcinog Risk l-42(Suppl 7), 1987 Cancer Treatments: Consider the Possibilities An easy-to-read brochure designed to make patients aware of clinical trials as a treatment option. Better Cancer Treatment M eans Improved Survival What are Clinical Trials A ll About? A 24-page booklet with information to help patients make informed decisions about participating in cancer clinical trials. Order these free publications by calling 1-800-4-CANCER or write to: Department CT National Cancer Institute Building 31, Room 10A24 Bethesda, Maryland 20892 Voi. 82, No. 7, April 4, 1990 I NCER ITUTE Cancer clinical trials provide the most up-to-date treatment available. You can use these publications from the National Cancer Institute to help your patients leam about this important treatment option. Please send me: _____ Cancer Treatments: Consider The Possibilities _____ What Are Clinical Trials AU About? Name________________________________________________ fWpnmrinr Address______________________________________________ C iry . 2531 EDITORIALS 545 2532 L 2. Environmental Health Monthly Voi. 2, NO. 6 March, 1990 Editorial Review Board L ob M arie Gibbs Arlington, VA Gary G illen, M.D. Circleville, O H Robert G lnsbarg, Ph.D. Chicago, IL M arc Lappe, Ph.D. Chicago, IL Penny Newman Riverside, CA Beverly Paigen, Ph.D. Bar Harbor, ME David Oxonoft, M.D. Boston, MA Jenette Sberm an, M.D. Alexandria, VA Managing Editor Stephen Lester Arlington, VA ABSTRACT Since the 1950s, marked differences between cancer mortality rates in rural and urban areas have been diminishing. One explanation is the dramatic increase in agricultural chemical use since the early 1950s. In this paper, C. Shannon Stokes and Kathy D. Brace examine the relationship between agricultural chemical use and five major categories of cancer mortality in rural U.S. counties. The authors identified and selected 1497 counties whose populations were likely to be exposed to agricultural chemicals if they met any one of the following factors: 1) the number of employed persons working in agriculture was equal to or greater than the mean number for all counties; 2 ) the county had a mean value or greater for land used in farming; or 3) the county had a mean value or greater for the dollar value of all agricultural products sold. Cancer rates for the 20-year period 1950-1969 were selected from data compiled by the National Cancer Institute from data provided by the National Center for Health Statistics. Cancers were groups into 5 categories: genital; urinary; lymphatic and hematopoietic; respiratory; and digestive. Only rates for white males were used in this study. Different variables were analyzed for each county including total acreage treated with insecticides, herbicides and fertilizers; percentage of labor force in mining; in manufacturing; rurality; median family income; median educational level; and the percentage of the total county population that was foreign-bom. Findings indicate that agricultural chemical use is related to cancer mortality. For three of the five cancer categories, agricultural use was the best predictor of cancer mortality. Herbicides were positively and significantly associated with genital, lymphatic and digestive cancer; insecticides had a strong positive relationship to respiratory cancer; fertilizer use was largely unrelated to cancer mortality with the exception of a modest negative association with digestive cancer. The authors discuss limitations in their study but also point out that cancer mortality rates tend to underestimate the disease experience of a population because the actual numbers of people with the disease at any given time is greater than the number of people who have died from it. These limitations do not diminish the primary findings that there is a significant relationship between agricultural chemical use and cancer mortality. Printedon Recycled Paper Citizens Clearinghouse for Hazardous Wastes, Inc. P.O. Box 926, Arlington, Virginia 22216 (703) 276-7070 2 534 1 3 Q' .. ^ \ 1 j t m + y \r i1 I i \n ,i i; ! !! *! i r i r \ I / \ >nr I! \ \ 1 .1 5%7- OF THE N A T I O N A L \ &Esag&Bsa April 4, 1990\ Volume 82 Number 7 CANCER INSTITUTE It****. Editorials News Commentary Review Articles r-4 T. Reports Contents In This Issue Dose-Intense Adjuvant Treatment of High-Risk Breast Cancer G. Bonadonna, P. Valagussa Herbicides and Non-Hodgkin's Lymphoma: New Evidence From a Study of Saskatchewan Farmers A. Biair 541 542, .544 Scientists Navigate Bermuda Triangle of Technology Transfer Search for NIH Director--Changes for NCI? Preconception Notion: Childhood Leukemia Risk Linked to Paternal Exponre Pap Smear System OK'd * Killer Antibodies Enter Clinical Trial Against Ovarian Cancer PDQ Osage Op Sullivan Criticizes Company for Courting Smokers at Tennis Matches Awards, Appointments, Announcements . V. .546 y Biomarkers as Intermediate End Points in Chemoprevention Trials S. M. Lippman, 1. S. Lee, R. Lotan, W. Hittelman, M. J. Wargovich, W. K. Hong 555 Dietary Factors and Risk of Breast Cancer Combined Analysis of 12 Case Control Studies G. R. Howe, T. Hirohata, T. G. Hisiop, J. M. Iscovich, J.-M. Yuan, K. Katsouyanni, etaL -,-561 Sixteen-Week Dose-Intense Chemotherapy in the Adjuvant Treatment of Breast Cancer M. D. Abeloff, R. A. Beveridge, R. C. Donehower, J. H. Fetting, N. E Davidson, G. G. Gordon, etaL Mortality Study of Canadian Male Farm Operators: Non-Hodgkin's Lymphoma Mortality and Agricultural Practices in Saskatchewan D. T. Wigle, R. M. Semenciw, K. Wilkins, D. Riedel, L Ritter, R I. Morrison, et a l - ,5 7 . .'. W* . .. . '>-'575 Highly Specific Prediction of Antineoplastic Drug Resistance With an In Vitro Assay Using Suprapharmacoiogic Drug Exposures D. H. Kent, L M. Weisenthal \.V 582' _:r rrT Inhibition of CoUagenotytic Activity and Metastasis of Tumor Cells by a Recombinant Human Tissue - Inhibitor of Metalloproteinase* 0 . A. Alvarez, D. F. CarmichaeL Y. A. DeClerck i-.f Subcellular Distribution of Cyclic Adenosine 3'^'-Mooophosphate-Bmding'Protein and Estrogen Receptors in Control Pituitaries and Estrogen-Induced Pituitary Tumors G. Piroli, L S. Weisenberg, C. Grillo, A. F. Dc Nicola V `r -r * * # 5 9 6 : Expression of the Progestin-Induced Fatty Add Synthetase hi Benign Mastopathie! and Cancer as Measured by RNA In Situ Hybridization D. Chalbos, C Escot, C. Joyeux, M.-J. Tissot-Canyon, A. Pages, H. Rochefort ' v--;*r -.Svci"; *'if?*'l*&J' 1a- _^. Overexpression of P-glycoprotein in Mammalian Tumor Cell Lines After Fractionated X Irradiation In Vitro & T. Hill, K. Deuchars, L K. Hosking, V. Ling, R. D. R Whelan Lymphocytes Stimulated With Recombinant Human Interleukin-Z: Relationship Between Motility 2535Into Protein Matrix and In Vivo Localization in Normal and Neoplastic Tissues of Mice S. Rainer , 612 (Comenu continued on back cover) Q - 2 3 P-a-t,2>Cp - - S 4 V ^ B P - f fca a.tr- . a. Mortality Study of Canadian Male Farm Operators: . Jon-Hodgkin's Lymphoma Mortality and Agricultural Practices in Saskatchewan Donald T. Wigle,* Robert M. Semenciw, Kathryn Wilkins, Dieter Riedel, Leonard Ritter, Howard I. Morrison, Yang Mao A cohort study of the mortality experience (1971-1985) of male Saskatchewan farmers has been conducted. This study involved linkage of records of the almost 70,000 male farmers identified on the 1971 Census of Agriculture and the corre sponding Census of Population to mortality records. Pesticide exposure indices for individual farm operators for the year 1970 were derived from the 1971 Census of Agriculture records. Although the cohort as a whole had no excess mortality for any specific causes of death, including nonHodgkin's lymphoma, significant dose-response relation ships were noted between risk of non-Hodgkin's lymphoma and acres sprayed in 1970 with herbicides, as well as with dollars spent on fuel and oil for farm purposes in 1970. Using Poisson regression modeling, we found that relative risks for ' ' highest level of herbicide use (>250 acres sprayed) and .1 purchased in 1970 (>$900) on farms less than 1,000 acres total area were 2.2 (95% confidence interval = 1.0-4.6) and 2.3 (95% confidence interval = 1.1-4.7), respectively. [J Natl Cancer Inst 82:575-582,1990] As an occupational group, farmers experience low overall mortality (/). However, fanners and rural populations have been reported to be at increased risk of developing cancers of the stomach, prostate, lip, brain, and skin; Hodgkin's disease; leuke mia; multiple myeloma; and non-Hodgkin's lymphoma (2-14). Farmers are exposed to a number of potential health hazards that require evaluation. These include zoonotic viruses, solvents, fuels and oils, paints, farm machinery, dust and molds, waste gases, etc. In addition, farmers are the largest population with direct occupational exposure to pesticides. Excess risk to farmers for non-Hodgkin's lymphoma has been reported from several studies (4 -6 ,1 1 -1 4 ). Death certificate case-control studies from Wisconsin (6) and New Zealand (5) found that risk was highest among younger farmers, while case-control studies in Iowa (8) and Tasmania (9) found the opposite. Of particular interest in this context is the case-control study of Schumacher (12), which indicated that the lymphocytic form of non-Hodgkin's lymphoma accounted for most of the risk in older fanners. A recent case-control study of Kansas farmers found a significant relationship between exposure to chlorophenoxy herbicides and risk of non-Hodgkin's lymphoma. The purpose of the Mortality Study of Canadian Male Farm Operators is to investigate the relationships between various farming practices and specific cancers. The cancers selected for study were those that have been implicated in previous investiga tions of farmers and other workers exposed to agricultural pesticides. Using data for Saskatchewan males, this initial paper presents analyses that focus on the relationship between agricul tural substances and practices and the risk of death from nonHodgkin's lymphomas. Saskatchewan was the first province in this Canada-wide study for which data were produced; mortality analyses for other Canadian provinces are under way. Methods Data Sources The four key data bases used in this linkage study were the 1971 Census of Agriculture, the 1971 Central Farm Register, the 1971 Census of Population, and the Canadian Mortality Data Base. The Census of Agriculture is an inventory of Canadian agricul ture taken every 5 years. In 1971, all farm, ranch, or other agricultural holdings of 1 acre or more with sales of agricultural products of at least $50 in the year previous to the census were included. A farm operator was defined as the person directly responsible for the agricultural operation of the farm, regardless of whether that individual was the owner. Incases of partnership, only one partner was considered to be the operator. The total number of farm operators in Saskatchewan in 1971 was 76,668, of whom 73,538 were male. The 1971 Census of Agriculture included some questions applicable to 1970. These questions included the number of acres Received June 26.1989; revised Novem ber 27, 1989; accepted Decem ber 22, 1989. . Laboratory Centre for Disease Control, Ottawa, ON. Canada. We thank Dr. David Bray, John Silins. Martha Fair, Deborah Jordan-Simpson. and Christine Poliquin of the Health Division. Statistics Canada; Ray Bollman, formerly of the Agriculture Division, Statistics Canada; Dr. John Davies and Joan Lindsay of the Bureau o f Chronic Disease Epidemiology, Laboratory Centre for Disease Control. Department of National Health and W elfare; Diane Robson of the Saskatchewan C ancer Registry; and the Provincial Registrars of Vital Statistics. Correspondence to: Donald T . W igle, M .D ., Laboratory Centre for Disease Control, Ottawa, ON, Canada K IA 0L2. Voi. 82, No. 7, April 4, 1990 2536 Vn ' l Y Q ' ^ARTICLES 575 5 sprayed with herbicides and insecticides, and expenditures paid for pesticides and for fuel and oil for farm operations. Questions in the Census of Agriculture applicable to 1971 related to the total acreage of land operated, the numberof acres of crops planted and acres fertilized, amount of livestock holdings, and farm machin ery owned. Data on direct exposure to pesticides were not available from the 1971 Census of Agriculture. Surrogates used were: (a) number of acres sprayed for the control of insects; (b ) number of acres sprayed for die control of weeds; and (c) cost of agricultural chemicals purchased. The 1971 Central Farm Register was created as a mailing list for agricultural questionnaires. It contains all farm operators identified on the 1971 Census of Agriculture. In addition to several agricultural variables used to target surveys, the Central Farm Register contains personal identifying information. Similar registers were created for the 1976 and 1981 Censuses of Agriculture. Linkage to the 1981 register allowed a live follow-up of farmers who had been identified on the 1971 Census of Agriculture. The Census of Population is a complete inventory of Canada's population taken every 5 years. The 1971 Census of Population consisted of two types of questionnaires: form 2A (short) and form 2B (long). The short form was administered at random to two thirds of the population, with the remaining one third receiving the long form. The short form contained 19 questions; six of these concerned population variables. The long form, in addition to the 19 questions found on the short form, included 50 questions related to socioeconomic conditions and 20 questions related to housing. Variables selected from the 1971 Census of Population included age and mother tongue (2A) and education and income (2B). The Canadian Mortality Data Base is a computerized file that contains information on all deaths that have occurred in Canada since 1950. Some information is also received that relates to Canadian residents who die in the United States. Record Linkage The assemblage of data related to the mortality experience of the farmer cohort involved the computerized record linkage of data from the Central Farm Register, the Census of Agriculture, the Census of Population, and the Canadian Mortality Data Base using the Generalized Iterative Record Linkage System (15) (GIRLS) of Statistics Canada. This linkage involved three steps: 1. Linkage of the 1971 Census of Agriculture, the 1971 Census of Population, and the 1971 Central Farm Register to unite agricultural, population, and per sonal identifying information on cohort members. 2. Linkage of the 1971 Central Farm Register to the 1981 Central Farm Register as a live follow-up of cohort members. 3. Linkage of the cohort file to the Mortality Data Base (1971-1985) to determine mortality. The objective of the live follow-up by linkage of the 1971 Central Farm Register to that of 1981 was primarily to improve the accuracy of the probabilistic death linkage. The rules for linkage incorporated the occurrence of any discrepancies in vital status between information in the Mortality Data Base and information in the 1981 Farm Register. The overall likelihood of a linkage being "true" would thus be lowered if the Mortality Data Base contained a record of a farm operator's death before 1981 while the FarmRegister of 1981 contained information pertaining to the farm operator. Statistical Analysis Results of this report are based on the mortality experience of male Saskatchewan farmers identified in the 1971 Censuses of Agriculture and Population, whose age was at least 35 years at some point during the follow-up period (June 1971 through December 1985). A total of 69,513 men met these criteria. The age 35 limit was imposed because there were no deaths due to non-Hodgkin's lymphoma among younger farm operators. Also, only 6% of such deaths among all Canadian males occurred before age 35. Standardized mortality ratios (SMRs) were calculated using external (Saskatchewan males) age-specific mortality rates with confidence intervals (CIs) based on the Poisson distribution (16). Internal comparisons used the Mantel-Haenszel risk ratio with CIs based on Cornfield's method (17,18). Tests for trend in relative risk (RR) with increasing exposure were performed by regressing the observed minus expected differences in exposure (16). Four exposure categories were created for continuous variables based on either exposure quartiles or no exposure plus exposure tertilcs. Models were fitted to the grouped data using Poisson regres sion analyses (1 9 ,2 0 ). This method models the logarithm of the mortality rate as a linear regression of the independent variables including interactions if necessary. The regression coefficients provide estimates of the RRs for the independent variables. Age and year of death were considered a priori to be confound ing variables. A number of farmpractices other than herbicide use or fuel expenditures and sociodemographic variables were eval uated for confounding, although none was known to be an independent risk factor. Farm practice variables that were evalu ated included the following: (a) acreage sprayed with insecti cides, (b) acreage treated with fertilizers, (c) expenditures on agricultural chemicals, (d ) number of agricultural workers em ployed, (e) acreage in small grains, ( / ) acreage in hay and fodder, and (g) total animal holdings. Results Farming Practices Major crop groups planted in Saskatchewan in 1971 included, in order of acreage, small grains, hay, other fodder crops, canola, and mustard seed. About 75% of farms reported growing 130 or more acres of small grains (table 1). Hay and other fodder crops as well as canola and mustard seed were reportedly grown in that year on about 35% of farms. Only 5% of farms reported spraying insecticides in 1970, whereas 49.4% of farms reported spraying herbicides. For farms over 300 acres, about 30% reported spraying herbicides in 1970 on more than 20% of total acreage (table 2). No expenditure for pesticides was reported by 46% of farms. Mortality: Overview Afterthe Central Farm Register and the linkage of the Censuses of Agriculture and Population were preprocessed, records of 2537 f - z f o - x - *i- ^ .Journal of the National Cancer Institute T ab le 1. D istribution o f acres planted in m ajo r cro p groups. Saskatchew an. 1971 A cres Farm s % '1 3 0 10-229 230-379 380+ None <30 30-69 70+ None <65 65-119 120+' - Small groins 17,592 17,298 17,964 17,245 Hay and other fodder crops 45.844 9,679 1222 7,354 Canola and mustard seed 46,232 8,902 7.632 7.333 25.1 24.7 25.6 24.6 65.4 13.8 10.3 10.5 66.0 12.7 10.9 10.5 70,099 male farm operators were available for the mortality linkage (95.3% of the male farm operators active in Saskatch ewan in 1971). Mortality rates among the 69,513 farm operators aged 35 or more for major causes of death were significantly below those for males in the province as a whole (table 3), with an SMR for all-cause mortality o f 0.74. The observed numbers of deaths among the farm operators were not significantly higher than expected for melanoma, brain cancer, multiple myeloma, and non-Hodgkin's lymphoma with SMRs of 1.05, 1.03, 1.02, and 0.92, respectively. Non-Hodgkin's Lymphoma RR estimates for such sociodemographic variables as mother tongue, education, and income and non-Hodgkin's lymphoma were calculated (table 4). The RR for German as mother tongue was 1.4 (95% Cl, 0.9-2.3), and for Ukrainian the RR was 1.6 (95% Cl, 0.9-2.7). Lower RRs were observed for the two thirds T otal farm size (acres) 0-49 50-299 300-599 600-999 ,0 0 0 + All farm s Tabic 2. No. o f farm s by % of total area sprayed with herbicide and total farm size, Saskatchewan, 1970* % total area sprayed 0 1-19 20-39 40-59 60-79 80+ 958 (96.0) 4,963 (68.8) 11307 (52.2) 10,776 (46.0) 7,458 (44.3) 35,462 (50.6) 1 (0.1) 418 (5.8) 3,101 0 4 .3 ) 4,974 (21.3) 4377 (27.2) 13.071 (18.6) 2 (0.1) 943 0 3 .1 ) 4.786 (22.1) 5,658 (24.2) 3.618 (21.5) 15.007 (21.4) 4 (0.4) 664 (9.2) 2,096 (9.7) 1,761 (75) 1,015 (6.0) 5540 (7.9) "2 (0.2) 141 (2.0) 275 0 .3 ) 183 (0.8) 116 (0.7) 717 0 .0 ) 31 (3.1) 87 0 .2 ) 81 (0.4) 53 (0.2) 50 (0.3) 302 (0.4) * V alues in parentheses = % o f farm s. T o ta l 998 (100.0) 7,216 (100.0) 21,646 (100.0) 23,405 (100.0) 16,834 (100.0) 70.099 0 0 0 .0 ) Table 3. Observed and expected No. of deaths am ong Saskatchewan farm ers aged 35 years or more. 1971-1985 Cause of death O bserved Expected* SMR Lower lim it 95% Cl Upper lim it All causes infective and parasitic All m alignant neoplasm s S tom ach T rachea, bronchus, lung Connective tissue M elanoma " P r o s t a t e .............. B rain Lym phoidt N on-H odgkin's lymphomas} L eukem ias M ultiple myeloma D iseases o f the circulatory system A ccidents, poisonings, violence 11.829 27 3.198 246 833 18 24 441 96 191 103 138 70 5,864 866 16.042.9 66.7 3.953.2 274.5 1,169.4 20.2 22.8 462.0 93.6 200.0 112.1 156.2 68.5 7,895.5 1.098.7 0.74 0.41 0.81 0.90 0.71 0.89 1.06 0.96 1.03 0.96 0.92 0.88 1.02 0.74 0.79 0.72 0.27 0.78 0.79 0.67 0.53 0.68 0.87 0.83 0.83 0.75 0.74 0.80 -0 .7 2 0.74 0.75 059 0.84 1.02 0.76 1.40 1.56 1.05 1.25 1.10 1.11 1.04 1.29 --U 6 6.84 'E x p ec te d No. of deaths based on age- and period-specific m ortality rates for Saskatchew an males, 1971-1985. 11CD (International Classification of D iseased, 200-203. 41CD9. 200, 202. 1CD 9, 2 0 4-206. 207.0, 207.2, 207.8. 208. Voi. 82, No. 7, April 4, 1990 2538 ARTICLES 577 T able 4. Analysis o f sociodem ographic variables and non-Hodglcin's lym phom as, based on internal standardization, for Saskatchew an fanners aged 35 years or m ore. 1971-1985 V ariable 1970 Incom e (S) <1300 7 ,5 0 0 -2 3 ,9 9 9 24,000-47,999 4 8 ,0 0 0 + Unknown Education (grades completed) 12+ 9-11 <9 ' Unknown M other tongue English French G erm an U k ra in ia n O ther Person years 76.352 80.025 70,490 78,105 573,006 95.672 162,916 46,384 573,006 510,436 38.932 140,794 95.177 92,640 O b serv ed deaths 9 14 17 13 50 12 30 11 50 51 3 22 16 11 RR** 1.0 0.77 0.60 0.84 0.43 1.0 1.15 0.88 0.52 1.0 0.78 1.43 1.56 0.96 Lower lim it 95% Cl Upper lim it 0.38 0.27 0.41 0.25 0.59 0.36 0.28 0.26 0.86 0.89 0.50 1.54 1.31 1.76 0.74 2.24 2.19 0.98 2.35 2.33 2.71 1.83 * M antel- H aenszel RR estim a te adjusted for age an d c a le n d a r yr. of persons for whom information on education and income was not available. The RR for unknown income was 0.4 (95% Cl, 0.3-0.7). However, the internal SMR for unknown income or education (those farmers who filled out the 2A census form) for all causes of death was 0.97. The results of univariate analyses of the risk of death due to non-Hodgkin's lymphoma, based on internal standardization, according to farm practices are presented in table 5. The RR estimates according to dollars spent in 1970 on fuel and oil for farm purposes indicated a significant trend with increasing expen ditures. The RR was 1.8 in the category $900 or more. No increase was noted according to the number of acres fertilized or to the number of acres in small grains, hay-other fodder crops, or canola-mustard (data not shown). RR estimates of 1.1,1.5, and 1.3, respectively, were observed for the categories 1-99, 100-249, and 250 or more acres sprayed T able 5. D ose-response analysis o f 1970-1971 fanning practices and non-H odgkin's lymphom as, based on internal standardization, for Saskatchewan farm ers aged 35 years or more, 1971-1985 Farm ing practice Person years O bserved deaths RR* Lower limit 95% Cl Upper limit Acres sprayed with herbicides. 1970T 0 1-99 100-249 250+ Dollars spent on pesticides. 1970t 0 1-49 50-109 110+ D ollars spent on fuel and oil for farm purposes, 1970 060 360-599 600-899 900+ 438.341 112.446 197,199 129,992 394,322 150,443 170,616 162,597 205,209 217,872 221,555 233.342 ' 46 14 28 15 44 15 25 19 22 23 27 31 1.0 l.l 1 1.47 1.34 1.0 0.88 1.49 1.19 1.0 1.18 1.45 1.83 0.62 0.94 0.74 0.49 0.92 0.70 0.66 0.81 1.03 2.00 2.41 2.38 1.57 2.45 2.04 2.13 2.55 3.25 578 * M antel-H aenszel RR estim ate adjusted for age and calendar yr. f < t T e s i fo r tren d ch i-sq u are 11 d f (degree o f freedom )) = 2 .3 1 , o n e -sid e d /* = .064. $ T e s t for tren d ch i-sq u are (1 d f) = 1.11, o n e-sid ed P = .146. v__________ T est for tren d c h i-sq u are (1 df) = 5.78, o n e-sid ed P = .008. 2539 Journal of the National Cancer Institute with herbicides. The use of insecticides was limited and only two non-Hodgkin's lymphoma deaths were observed in the group that reported spraying. Interaction was noted between size of farmand acres sprayed with herbicides. An insignificant decreased risk was noted for operators of farms greater than 1,000 acres. A itive dose-response relationship between acres sprayed with ,,oicides and risk of dying of non-Hodgkin's lymphoma was evident when the analysis was restricted to farms under 1,000 acres. The test for trend with increasing acres sprayed with herbicides was significant (one-sided P value = .002) (table 6). To further study the relationship between non-Hodgkin's lymphoma mortality and acres sprayed with herbicides, we calculated attributable risks. On farms smaller than 1,000 acres, the amount of non-Hodgkin's lymphoma associated with herbi cide spraying among farm operators was 27% and on all farms it was 22% (21). To adjust for the possible effects ofjoint confounding, we used Poisson regression modeling. Data presented are based on a model including strata for the following categories: number of acres sprayed with herbicides, area of farm, expenditures on fuel and oil, age of farm operator, and calendar year. The multiplica tive model provided a superior fit compared to an additive model and was consequently used for the Poisson regression analyses. RR estimates for farms of less than 1,000 acres are presented in table 7. Estimates for 100-249 and 250 or more acres sprayed with herbicides were 1.9 (95% Cl = 1.2-3.3) and 2.2 (95% Cl = 1.0-4.6), respectively. The highest fuel and oil expendi tures category was associated with an RR of 2.3 (95% Cl = 1.1-4.7). Trend tests obtained using a continuous exposure variable were significant for the number of acres sprayed with `--rbicides [chi-square (1 df) = 6.5, one-sided P = .005] and A of farm fuel and oil [chi-square (1 df) = 10.99, one-sided r < .001]. In the time period 1981-1985, theRR was 1.6, which was higher, but not significantly, than in the time periods T able 6. O bserved deaths and RR* due to non-H odgkin's lymphom a 1971-1985, by farm size and acres sprayed with herbicides in Saskatchew an, 1970-1971 Acres sprayed Farm size < 1,000 acres >1,000 acres All farm s 0 D eath s RR 1-99 D eath s RR (95% C l) 100-249 D eath s RR (95% CD 250+ D eath s RR (95% CD hi-square for trend 'o n e -ta ile d ) 35 1.0 14 1.31 (0 .7 1 .2 .4 0 ) 28 1.92 (1.18, 3.18) 10 2.14 (1 .0 5 ,4 .2 4 ) 8.32 .002 11 1.0 0 0.00 (0.00, 2.85) 0 0.00 (0.00, 1.01) 5 0.60 (0.22. 1.68) 1.00 .159 46 1.0 14 1.11 (0.62. 2.00) 28 t .47 (0 .9 4 ,2 .4 1 ) 15 1.34 (0.74, 2.38) 2.31 .064 * M antel-H acnszel RR estim ate adjusted for age and calendar yr. T able 7. RRs (95% C l) from m ultivariate Poisson regression analysis of non-H odgkin's lym phom a, restricted to farm s less than 1.000 acres, Saskatchewan farmers. 1971-1985 RR 95% Cl Variable fuel cost, 1970 <S360* S360-S599 S600-S899 $900+ na _u_u_ _)_U__i__y_cju wiiii 1iiciuiciuc, %i7n#nnv 0* 1-99 100-249 250+ "Year 1971-1975* 1976-1980 1981-1985 Area o f farm . 1971 < 3 0 0 acres* 300-599 acres 600-999 acres 1.0 1.28 1.87 2.29 1.0 1.31 1.93 2.17 . 1.0 0.96 1.64 1.0 0.65 0.50 0 .6 9 .2 .3 9 0.98. 3.58 1.11,4.73 0.70,2.43 1.15, 3.25 1.02,4.62 0 .5 1 ,4 .6 2 0.93, 2.89 0 .3 4 , 1.23 0.25, 1.04 R eference category. 1971-1975 and 1976-1980. RR estimates for acres sprayed with herbicides on farms of 1,000 acres or more were less than 1.0. A test for multiplicative interaction showed the interaction of the RR estimates according to expenditures on agricultural chem icals with farm size to be weaker than the interaction between acres sprayed with herbicides and farm size, and was insignifi cant. When restricted to farms under 1,000 acres, the dose-re sponse relationship remained insignificant. For all farms, the RR estimates for the third and fourth quartiles were 1.4 (95% Cl = 0.9-2.4) and 1.2 (95% Cl = 0.7-2.1), respectively. Models were also constructed to include sociodemographic variables (education, income, and mother tongue). Results were similar to those in which these terms were dropped. Accordingly, as they were not found to confound the exposure-disease relation ship,.the final models dropped these variables in order to increase precision. Mortality rates for other cancers (as listed in table 3) were examined at the four levels of the two variables: number of acres sprayed with herbicides and expenditures for fuel and oil. No other positive associations were observed. Significant negative trends in lung cancer mortality were observed with increasing levels of numbers of acres sprayed with herbicides and with increasing fuel expenditures. Discussion In this study of Saskatchewan farm operators, overall death rates were considerably lower than for males in the general population of the province. This result is consistent with previ ously reported lower overall mortality rates among farmers (7). This finding probably reflects several factors: a "healthy worker" effect, the low prevalence of smoking among Canadian farmers (unpublished tabulations from the National Farmers Survey, 1984, Statistics Canada Agriculture Division), and a failure to identify all deaths in the Mortality Data Base. It was assumed that if the record of a person's death was not found through comput- V ol. 82, N o. 7 , April 4 , 1990 2540 ARTICLES 579 erized record linkage in the Mortality Data Base, then the person was still alive. This might be false because either the person died outside of Canada and his death record was not forwarded to Statistics Canada, or, more likely, inadequate personal identifiers on the census records resulted in the failure to link mortality records to input records. From the results of a recent evaluation of linkage error in another study, based on the number of personal identifiers available (22), we expect that in the present study we missed up to 10%-15% of the deaths that occurred. However, because internal comparisons were used to further study mortality patterns, incomplete follow-up should not have affected the results because there is no reason to expect that loss to follow-up was associated with the variables of interest. Investigation of mortality patterns within the group of farm operators revealed a significant dose-response relationship be tween exposure to certain farming-related practices in 1970-1971 and subsequent death due to non-Hodgkin's lymphoma. NonHodgkin's lymphoma mortality was significantly associated with increases in levels of two exposure variables: the number of acres sprayed with herbicide and expenditures on fuel and oil in 1970. While increased risks were associated with increased numbers of acres sprayed for weeds, increased risks were not noted in relation to total expenditure on agricultural chemicals. This inconsistency might be due to the crudeness of the latter as an index of herbicide exposure. In addition, agriculture production statistics indicate that wheat production in Saskatchewan in 1970 was 52% lower than in 1969; sales of herbicide and fertilizer materials, for example, were correspondingly below the level of 1969, reflect ing the decrease in seeding and production for 1970 (22-24). Throughout the 1960s and 1970s, respectively, the chlorophenoxy compound 2,4-D constituted over 90% and 75%, by weight of all herbicide active ingredients used agriculturally in Saskatch ewan. The herbicide 2,4,5-T was apparently used infrequently in agriculture in Saskatchewan at this time, although it was in regular use for brush control on non-crop land (25,26). Until the 1950s, sodium chlorate, sodium arsenite, sulfuric acid, and dinitrophenols were also used as agricultural herbicides. Herbi cide treatments in grain crops have also included other chemicals such as bromoxynil, cyanazine, dicamba, linuron, metribuzin, and propanil (27). Furthermore, solvents such as kerosene have been used in some herbicide formulations (26). The use of tractors or other automotive equipment in spraying operations would result in the simultaneous exposure of the applicators to exhaust emissions as well as to pesticide-laden dust or pesticide spray droplets. This dual exposure, along with the limited spraying indices available in this study, makes it difficult to assess the separate contribution of each to the outcome. It is noteworthy, however, that there was no elevation of risk of non-Hodgkin's lymphoma mortality associated with fertilizer application, most of which is done by tractor. In addition, no increase in lung cancer mortality was associated with the surro gate variable for fuel exposure, as might have been expected from the findings of other studies (28,29). Interpretation of the findings of the present study is somewhat complicated by the lack of consistent results of animal experi mentation. An increased incidence of splenic malignant lym phoma has been observed among rats exposed to diesel exhaust fumes (30). Also, 1,6-dinitropyrenc, a diesel fuel combustion product, has caused malignant fibrous histiocytomas in mice (31). However, in a series of studies on rats exposed to diesel exhaust or fractions thereof, most did not show any evidence of lymphoid malignancies (32). Similarly, no increase in lymphoid tumor incidence occurred among rats exposed to the 2,4-D acid used in herbicides, although the incidence of astrocytoma brain tumors increased (Serota DG, et al: unpublished data in the report, "Combined toxicity and oncogenicity study in rats--2,4dichlorophcnoxyacclic acid," submitted to Industry Task Force on 2,4-D Research Data, May 29,1986). The differential effect of herbicide spraying according to farm size raises several questions related to farming practices. The RR of non-Hodgkin's lymphoma as a function of farm size declined sharply for farms larger than 1,000 acres, although on farms smaller than 1,000 acres there was a significant increase in risk for non-Hodgkin's lymphoma when expressed as a function of acres sprayed for weeds. The causal significance of these obser vations cannot be fully assessed due to the paucity of data on the use of hired applicators to carry out weed spraying operations. Moreover, on large farms, an appreciable proportion of pesticides might be applied by aircraft. The major limitation of this study is the potential to misclassify exposure status. Several factors may have contributed to this limitation. Analysis was based only on self-reported fanning exposure data from 1970-1971, though about 25% of the farm operators also reported income from off-farm work in that year. However, there was not a significant difference in the SMR of non-Hodgkin's lymphoma deaths between those farm operators who reported working off the farm and those who did not. Departure from fanning and year-to-year variation of farm practices also contributed to misclassification of exposure. It is estimated that 30% of males who were farm operators in Saskatchewan in 1966 had left farming by 1976 (33). In addition, herbicide use was lower in Saskatchewan in 1970 than in the years prior to and following that year due to a grain surplus and federal incentives to reduce production (24,25). Therefore, the extent to which the 1970 exposure estimates reflect long-term environmen tal exposure responsible for the observed elevated risks is not known. Fifty percent of the farm operators reported no use of herbicides in 1970, but it is virtually certain that many of these men did use herbicides in previous and subsequent years.. The effect of non-differential misclassification of exposure is to bias the RR estimate toward unity. The true risk to farm operators, then, is likely to be larger than that observed. Missed mortality links would result in lower estimates for the cohort as a whole but should not cause a bias in comparisons within the cohort. Misclassilication with regard to disease status was considered, as ascertainment was by way of death certificates rather than through histologically confirmed incident cases. In order to check for " false positives" among the 103 deaths attributed to nonHodgkin's lymphoma, the non-Hodgkin's lymphoma death records used in this study were linked to records of the Saskatch ewan Cancer Registry. In 98 of the 103 cases, diagnosis of non-Hodgkin's lymphoma was noted in the registry records. Of the remaining five persons, lymphoid leukemia had been diag nosed for two, and a variety of other cancers were noted in the records of the other three. Therefore, in the present study, false positive misdiagnosis would not be expected to affect more than about 5% of the deaths attributed to non-Hodgkin's lymphoma. 2 5 4 1 p, y q80 Journal of the National Cancer Institute Efforts were also made to check, at least partially, for the ' possibility of " false negatives," i.e., deaths due to non- Hodgkin's lymphoma that were misdiagnosed as another cancer. All records attributing death to chronic lymphoid leukemia, a disease with which non-Hodgkin's lymphoma might reasonably be diagnostically confused, were compared with cancer registry records for possible diagnoses of non-Hodgkin's lymphoma. No such diagnoses were recorded for the 44 males in the analytic file whose death was attributed to chronic lymphoid leukemia. Thus, it seems reasonable to conclude that misclassification with regard to disease status was not a major source of bias in this study. Several previous investigations have been carried out as casecontrol studies and can be criticized for possible recall bias. The design of the present investigation as a cohort study obviates recall bias as a concern. There is little reason to believe that the extent of herbicide- or fuel-related exposure, or the accuracy of reporting such exposure-related information in the 1971 census, would have been affected by the subsequent mortality experience within this cohort. Case response bias would occur if exposure were differentially reported by farm operators with prevalent non-Hodgkin's lymphoma in 1971. However, in the period 1981-1985, the risk estimate was actually higher than in the earlier periods, and restriction of the analysis to deaths that occurred after 1976 resulted in increasing the magnitude of the risk estimates. These results suggest that the reported level of herbicide exposure was not associated with the prevalence of disease. An increased risk of non-Hodgkin's lymphoma to farmers has been reported by several studies from Australia, Canada, Europe, New Zealand, and the United States {4 -6 ,1 1 -1 4 ). A casecontrol study conducted in western Washington found RRs of incident cases of non-Hodgkin's lymphoma of 1.3 (95% Cl = 1.0-1.7) among men who had worked as farmers (77), though no association between increased risk and exposure to herbicides was observed. A study carried out in Kansas, however, found a strong dose-response association between frequency of herbicide use and incident non-Hodgkin's lymphoma, increasing from an odds ratio of 1.4 among farmers exposed between I and 5 days per year to 6.0 among those exposed for 21 days or more per year (4). The percentage of non-Hodgkin's lymphoma risk attributable to herbicide exposure was calculated as 11%, which was some what lower than the attributable risk estimates in the present study of 27% and 22%, respectively, among farmers on farms smaller than 1,000 acres and on all farms. In contrast to findings of the present study, no association was observed in the Kansas study between non-Hodgkin's lymphoma risk and acreage sprayed with herbicides. Perhaps such discrepancies in results between the two studies reflect differences in design. A subsequent investigation in Nebraska revealed a non-signif icant 50% increase in risk of non-Hodgkin's lymphoma among men who had used the herbicide 2,4-D in agriculture {34). In a case-control study in New Zealand, the case group contained a significant excess of the occupational category involving agricul ture and forestry (odds ratio = 1.3,95% Cl = 1.0-3.0) (5). No association was seen in the New Zealand data, however, between non-Hodgkin's lymphoma and either duration or frequency of phenoxy herbicide use {35). A Swedish case-control study of non-Hodgkin's lymphoma noted increased risks to workers ex posed to phenoxyacetic acid herbicides and chlorophenols {36). A more recent study confirmed the association with phenoxy acids and also identified occupational exposure to solvents, creosote, and wood-working as risk factors {37). The Kansas study revealed a rising risk of non-Hodgkin's lymphoma with increasing time since first exposure to herbicides {4). The authors noted that it is not known whether this risk pattern reflects a long induction period between exposure and disease, possibly dependent on the presence of carcinogenic impurities in the early formulations of herbicide, or a shorter induction period combined with increased herbicide exposure during recent years. Unfortunately, latency issues could not be addressed in the present study because year of first exposure and length of exposure were not available. On the whole, the findings of this and previous studies are consistent with a hypothesis of increased risk of non-Hodgkin's lymphoma in association with spraying herbicide formulations. This is the first study to report an association between nonHodgkin's lymphoma and exposure to fuel and oil. On this basis, it would seem prudent to educate farm families in the safe handling of these substances. The magnitude of risk for Saskatchewan farmers is probably greater than that reflected in the estimates in this study, due to the likelihood of misclassification of exposure. There is a particular need for further studies in this area to improve the quantification of farming-related exposures, and to study the exposure history of individuals who develop non-Hodgkin's lymphoma. References ( / ) Bi.air A, Malker H . Cantor K P, et al: C ancer am ong fanners: A review. Scand J W ork Environ H ealth 11:397--407, 1985 (2) Blair A , White DW-. Leukem ia cell types and agricultural practices in Nebraska. Arch Environ Health 40:211-214,1985 (3) M ilham S: Leukem ia and multiple myeloma in farm ers. Am J Epidemiol 94:207-210.1971 (4) Hoar SK , Blair A , Holmes FF , et al: Agricultural herbicide use and risk o f lymphoma and soft-tissue sarcom a (published erratum appears in JAM A 256:3351, 1986). JA M A 256:1141-1147, 1986 (5) Pearce NE, Smith A H , Fisher DO: M alignant lym phom a and multiple myeloma linked with agricultural occupations in a New Zealand Cancer Registry-based study. A m J Epidem iol 121:225-237, 1985 (6) Cantor KP: Farm ing and m ortality from non-H odgkin's lymphoma: A case-control study, lnt J C ancer 29:239-247, 1982 (7) Burmeister L F, Van L ier SF, Isacson P: Leukem ia and farm practices in Iowa. Am J Epidemiol 115:720-728,1982 (5) Burmeister LF. Everett GD, Van Lier SF, et al: Selected cancer m ortality and farm practices in Iowa. Am J Epidemiol 118:72-77, 1983 (9) Giles GG. Ljckiss JN , Baikie M J, et al: M yeloproliferative and lym- phoproliferative disorders in Tasmania, 1972-80: Occupational and familial aspects. JNCI 72:1233-1240,1984 (10) Delzell E, Grufferman S: M ortality among white and nonwhite farmers in North C arolina, 1976-1978. Am J Epidem iol 121:391-402, 1985 (11) W oods JS , Polissar L , Severson RK, et al: Soft tissue sarcom a and non-H odgkin's lym phom a in relation to phenoxyherbicide and chlorinated phenol exposure in w estern W ashington. JN CI 78:8 9 9 -9 1 0 , 1987 (12) Schumacher MC: Farm ing occupations and m ortality from non-H odgkin's lym phom a in Utah. A case-control study. J O ccup Med 27 :5 8 0 -5 8 4 , 1985 (13) Buesching D P, Wollstadt L: L e tte r C ancer m ortality among farmers. JNCI 72:503-504, 1984 (14) Gallagher R P, Threlfall W J, Jeffries E , et al: C ancer and aplastic anemia in British C olum bia fanners. JNCI 72:1311-1315, 1984 (15) Howe G R . Lindsay J: A generalized iterative record linkage computer system for use in medical follow-up studies. Comput Bioincd Res 14:327-340, 1981 (16) Breslow NE, Day N E: Statistical M ethods in C ancer R esearch. Volume II: The Design and Analysis o f Cohon Studies. 1ARC Sci Publ No. 82. Lyon: ' IARC, 1988, pp 82-118 (17) Kleinbaum D G , Kupper L L , Morgenstern H: Epidem iologic Research. Belmont, CA: Lifetime Learning, 1982, pp 321-376 V ol. 82, N o. 7 , April 4 , 1990 2542 ARTICLES 58 9-ti (S) Guess H A , L ydick E G . Small R D , et al: Epidem iologic programs for computers and calculators. Exact binomial confidence intervals for the relative risk in follow-up studies with sparsely stratified incidence density data. Am J Epidem iol 125:340-347, 1987 (79) Breslow N E . Day NE: Statistical M ethods in Cancer Research. Volume II: The Design and Analysis o f Cohort Studies. 1ARC Sci Publ No. 82. Lyon: IARC, 1988, pp 120-176 (20) Numerical Algorithms Group, Ltd : The GLIM System , release 3.77. Oxford: Num erical Algorithm s G roup, L td., 1987 (21) Ki-Einbaum DG, Kupper L L. Morgenstern H: Epidemiologic Research. Beim oni, CA: Lifetim e Learning, 1982, p 163 (22) Fair M E, LaLonde P: M issing Identifiers and the Accuracy o f Individual Follow-up: Statistics Canada Symposium on Statistical Uses of Administra tive D ata. N ovem ber 1987. Ottawa: Statistics Canada. 1987 (23) Dominion Bureau oi: Statistics: Quarterly Bulletin of Agricultural Statis tics, O ctober-D ecem bcr 1970. Cat No. 21-003. Ottawa: Information C an ada. 1971 (24) Dominion Bureau of Statistics: Quarterly Bulletin o f Agricultural Statis tics, A pril-June 1971. Cat No. 21 -0 0 3 . Ottawa: Information Canada. 1971 (25) Manitoba Department of Agriculture: Agricultural Statistics: Annual Herbicide Use Surveys, 1955-1986. Winnipeg: Manitoba Dept of Agricul ture (26) Control Products Section, Agriculture Canada: Summaries o f Uses for 2,4-D and 2,4,5-T and Fenoprop Registered Under the Pest Control Products Act. Ottaw a: Agriculture C anada, 1978 (27) National Executive Expert Committee on Welds: A Statement of the Expen Committee on Weeds: Position on Herbicide Use. Ottawa: Agricul ture Canada, 1980, pp 6 -7 (28) McDuffie HH, Klaassen DJ, Cockroft DW. et al: Farming and exposure to chemicals in male lung cancer patiente and their siblings. J Occun Med 30:55-59,1988 (2V) Stt-.MiATYCKi J. GF.rin M. Stewart P, et al: Associations between several sites of cancer and ten types of exhaust and combustion products. Scand J W ork Environ Health 14:79-90, 1988 ( 50) Iwai K. Udagawa T . Vamagishi M, et al: Long-term inhalation studies of diesel exhaust on F344 SPF rats. Incidence o f lung cancer and lymphoma, /n Carcinogenic and Mutagenic Effects o f Diesel Engine Exhaust (lshinishi N, Koizumi A. McClellan RO, et al. eds). Amsterdam: Elsevier, pp 349-360 1986 ( 3 1 ) Tokiwa H. Orol tiJi T. Nakagawa R, et al: Dinitro derivatives o f pyrene and fluoranthene in diesel emission particulates and their tumorigenicity in mice and rats. In Carcinogenic and Mutagenic Effects of Diesel Engine Exhaust (lshinishi N, Koizumi A, McClellan RO, et al, eds). Amsterdam: Elsevier. 1986. p 263 (22) IsitiNisiii N. Koizumi A . McClellan RO. et al, eds: Carcinogenic and Mutagenic Effects of Diesel Engine Exhaust. Amsterdam: Elsevier. 1986 (32) Bollman R. Steeves AD: The stocks and flows o f Canadian census farm operators, 1966-76. Can Rev Soc Anthropol 19:576-590, 1982 (34) Hoar Zaiim S, Weisenburger DD, Babbitt PA , et al: A case-control study of non-H odgkin's lymphom a and agricultural factors in eastern Nebraska. Am J Epidem iol 128:901, 1988 (35) Pearce N: Letter: Phenoxy herbicides and non-H odgkin's lymphoma in New Zealand: Frequency and duration o f herbicide use. Br J Ind Med 46:143-144, 1989 (36) Hardeu. L. Eriksson M. Lenner P. et al: Malignant lymphoma and exposure to chemicals, especially organic solvents, chlorophcnols and phenoxy acids: A case-control study. Br J C ancer 43 :169-176, 1981 (37) Persson B. Daiilander A-M , Fredriksson M , et al: Malignant lympho m as and occupational exposures. Br J Ind Med 4 6 :5 1 6 -5 2 0 . 1989 Highly Specific Prediction of Antineoplastic Drug Resistance With an In Vitro Assay Using Suprapharmacologic Drug Exposures David H. K ern* Larry M. Weisenthal Bayes' theorem has been used to describe the relationship between the accuracy of a predictive test (posttest probabil ity) and the overall incidence of what is being tested (pretest probability). Bayes' theorem indicates that laboratory assays will be accurate in the prediction of clinical drug resistance in tumors with high overall response rates (c.g., previously untreated breast cancer) o n ly when the assays are extremely (>98%) specific for drug resistance. We developed a highly specific drug-resistance assay in which human tumor colonics were cultured in soft agar and drugs were tested at high concentrations for long exposure times. Coefficients for con centration x time exceeded those reported in contemporane ous studies by about 100-fold. We reviewed 450 correlations between assay results and clinical response over an 8-year period. Results were analyzed by subsets, including different tumor histologies, single agents, and drug combinations. Extreme drug resistance (an assay result > SD below the median) was identified with greater than 99% specificity. Only one of 127 patients with tumors showing extreme drug resistance responded to chemotherapy. This negligible posttest probability of response was independent of pretest (ex pected) probability of response. Once this population of patients with tumors showing extreme drug resistance had been identified, posttest response probabilities Tor the re maining cohorts of patients varied according to both assay results and pretest response probabilities, precisely accord ing to predictions based on Bayes' theorem. This finding allowed the construction of a nomogram for determining assav-predictcd probability of response. IJ Natl Cancer Inst 82:582-588,1990] Perhaps the major reason cancer chemosensitivity testing has not become routine clinical practice is the perception that the Received November 7 ,1 9 8 9 ; revised Decem ber 18,1989; accepted Decembe: 26.1989. Supported by Public Health Service grant CM -57710 from the National Cance Institute. National Institutes of Health. Department o f Health and Humai Services, and by the Veterans Administration. Oncotech. Inc.. Irvine. CA. We thank lan Tannock and Donna Neuberg for their helpful suggestions. Correspondence to: David H . K em . P h .D .. O ncotech. In c .. 1791 Kaiser Ave Irvine. CA 92714. 2543 9 - s i *Journal o f the N ational C ancer Institut ti 2544 IH o -^ Federated Mutual began investigating the fire and notified LPC that it intended to pursue subrogation claims. When Federated Mutual later tried to examine the equipment that had allegedly caused the fire, it learned that the equipment had been discarded. Federated Mutual did not pursue the subrogation claim. However, it sued LPC and its insurer's attorneys, who had arranged for storage of the destroyed equipment. Plain tiff alleged, in part, negligent and intentional spoliation o f evidence. Defendants moved to dismiss, claiming that Minnesota did not recognize a cause o f action for spoli ation o f evidence. The trial court denied the motion. However, it certified to the state supreme court the ques tion o f whether claims for negligent or intentional spoli ation o f evidence could be brought in the state. The Supreme Court o f Minnesota declined to recognize the torts given the procedural posture o f the case. Noting that a tort does not become actionable until wrongful conduct causes an injury, the court concluded that a party bringing a spoliation action must first adjudicate its under lying claim to prove that it has sustained a cognizable in jury. The court reasoned that it would be inappropriate to award damages for the destruction o f evidence that would not have been helpful in establishing a claim. Moreover, the court observed that a party can some times avoid injury by using traditional remedies for the destruction o f evidence As an example, it cited an eviden tiary rule permitting a fact finder to infer that evidence destroyed while in one party's possession was adverse to that party. Here, the court reasoned, plaintiff might have prevailed on its subrogation c la im had it used that adverse inference and other traditional remedies. Given the lack o f precedent in the state for a spoliation cause o f action and plaintiff's failure to first adjudicate the subrogation claim, the court concluded that the trial court should have dismissed the case. Nonmedical expert witness with adequate train ing, education, and experience could express novel cancer-causation theories. Bubanick v. Witco Chcm. Corp., 576 A .2d 4 (N.J. Super. Ct. App. Div. 1990). Two men died from colon cancer after they were exposed to PCBs at work. Their survivors sued their employer and the company that had sold the PCBs. In support o f their claim that the PCBs had caused the cancer, plaintiffs planned to call Balis, a biochemist who had done exten sive research in cancer causation. At an in limine hearing addressing challenges to Balis' competence and qualifications, the court determined that Balis could only give his opinion as to human carcino genesis in general. Because he was not a physician, the court found that he was not qualified to testify about the cause o f the men's cancers because he lacked the requisite education, training, and experience. Moreover, the court ruled that he could not testify that PCBs had caused the cancers because his theory was a novel scientific opinion that had not been accepted by at least a substantial minor ity o f the scientific community. The court then granted defendants' summary judgment motion, concluding that plaintiffs would be unable to prove their case without this testimony. A New Jersey appellate court reversed, finding that the trial court had improperly usurped the jury's prerogative as a fact-finder. It held that Balis' knowledge, training, and experience qualified him to testify on cancer develop ment and related scientific matters. It determined that the jury must decide the weight given to any deficiencies stemming from his lack o f a medical degree or experience in treating cancer patients. The court also found that the jury should have been permitted to evaluate Balis' causation theory. The court said that when a qualified expert presents a well-reasoned causation theory based on his or her education, training, and experience, and developed in accordance with sound methodology, it is not necessary that the opinion be gen erally accepted in the scientific community. It concluded that an expert's testimony is admissible as long as the theory is not so outlandish, illogical, or totally speculative that no reasonable jury could accept it. Lack o f agreement within the scientific community goes to the weight o f the testimony--not its admissibility. Plaintiffs' Counsel: Alfred A. Russo, Trenton, N.J. Timothy M. Casey, Trenton, N.J. Expert's testimony was admissible despite the lack o f epidemiological evidence linking chemical ex posure to colon cancer. Christophmen v. AUied-Signal Corp., 902 F.2d 362 (5th Cir. 1990). Christophcrsen, who was allegedly exposed to nickel and cadmium fumes at work, developed colon cancer. After he died, his survivors sued his employer and its chemical suppliers, alleging that Christophersen's cancer had been caused by the exposure. Plaintiffs' expert, Miller, prepared an affidavit supporting that causation theory. Defendants moved to dismiss, claiming that Miller's opinion, which was essential to plaintiffs' claim, was unreliable because it was not supported by epidemiological studies showing a statistically significant link between nickel and cadmium exposure and colon cancer. The trial court granted the motion. The Fifth Circuit Court o f Appeals reversed, finding that, generally, expert testimony regarding causation need not be backed by epidemiological evidence showing a sta- 33 LAW REPORTER 2545373 NOVEMBER 1990 Q. nstically significant relationship between exposure and ill ness. The court refused to extend Brock v. Merrell Dow Pharmaceuticals, Inc., 874 F.2d 166 (5th Cir. 1989), 9 PLLR26 (Mar. 1990), which had required a plaintiff to show such epidemiological proof linking Bendectin with abnormal human developm ent. Characterizing that case as an exception to the general rule, the Fifth Circuit ob served that the Brock court had specifically declined to hold that epidemiological proofwas a necessary element in all toxic tort cases. Here, the court found that a medical expert's opinion in a toxic tort case is admissible as long as it is based on well-founded methodology. Noting that Miller had based his conclusion on m ethodologies traditionally used by physicians to determine the cause o f a patient's cancer, the court held that his testimony should have been pre sented to a jury. Plaintiffs' Counsel: Paul Colley, Jr., Tyler, Tex. [Comment. For a similar result, seeDrnlttn v. Indian Head Cranberries, Inc. (Mass., Plymouth Countv Superior Court, Feb. 26, 1990) (unpublished), 9 PLLR110 (July 1990), in which a trial court permitted toxicological studies link ing pancreatic cancer with pesticide exposure over defen dants' protests that the studies were not adequately sup ported by epidemiological data.) Expert's failure to use a specific term did not pre clude a finding th at asbestos exposure had sub stantially contributed to a cancer death. Abbott v. Babcock i f Wilcox Co., 905 F.2d 201 (8th Cir. 1990). Abbott was allegedly exposed to asbestos at work. After he died o f lung cancer, his family sued an asbestos manu facturer, claiming that his cancer had been caused by as bestos exposure. At trial, plaintiffs' expert, Tutcur, testi fied that A bbott's exposure had been a " contributing factor" to his lung cancer death. Defendant moved for a directed verdict, arguing in part that Missouri law requires that a contributing factor " sub stantially" contribute to a death before liability attaches. It claimed that Tuteur's testimony could only support a finding that the asbestos had been a cause and not a substantial cause o f Abbott's death. The trial court denied the m otion, and the jury awarded damages. The Eighth Circuit Court o f Appeals affirmed. The court stated that even if proof that a factor substantially contributed to a death is required to incur liability under Missouri law, it is not necessary for an expert to use the term " substantially contributing factor" to satisfy that standard. It was for the jury to evaluate the expert's testi mony to determine whether it demonstrated that defen dant's product had been a substantial cause o f death. The court concluded that Tutcur's testimony had been suffi cient to support the jury verdict. Plaintiffs' Counsel: Thomas H . Kart, III, Saint Croix, V.I. [Plaintiffs' appellate brief is available through the Offer ings section at p. 398, courtesy o f Mr. Hart.] Fa m il y L a w Supporting spouse was entitled to reimbursement o f contributions to her husband's education th at exceeded her minimum legal support obligations. Bold v. Bold, 574 A .2d 552 (Pa. 1990). While Mr. Bold was in college, he received about $32,000 in educational benefits and earnings, and Ms. Bold earned about S97,000. Shortly after Mr. Bold completed school, he asked Ms. Bold to move out o f their home. When they were later divorced, the court ordered Mr. Bold to pay Ms. Bold $33,000 as equitable reimbursement for the amount that her financial contributions to the family had exceeded his during the time he was in school. The appellate court reversed, finding that equitable re imbursement was only available where one spouse had been unjustly enriched by the financial contributions o f the other spouse that exceeded the support required by law. The court reasoned that because Ms. Bold had not paid any o f Mr. Bold's academic expenses, and her con tributions had not exceeded those that she was required to make, she was not entided to reimbursement. Reversing, the Supreme Court o f Pennsylvania noted that the Bolds had separated just as Mr. Bold had begun to realize the earning potential gained from his education. The court reasoned that in such a case, a supporting spouse justifiably feels exploited and is entided to reim bursement. However, the court found that the enridem ent must be balanced against that spouse's legally im posed support obligadon. Thus, the court held that a supporting spouse is entided to equitable reimbursement to the extent that his or her contribution to the educa tion, training, or increased earning power o f the other spouse exceeded the bare minimum that the supporting spouse was legally obligated to contribute to the marriage. The court commented that in determining whether a supporting spouse should be reimbursed, a trial court should consider the length o f time that the parties were married after the supported spouse began to realize his or her earning capacity and the use to which such earnings were put during that rime. It then remanded the case for a determination o f the amount by which Ms. Bold's con tributions had exceeded the legally imposed minimums. M s. Bold's Counsel: John R Greisamer, Allentown, Pa. NOVEMBER 1990 374 33 LAW REPORTER 2546 a * . * 2547 II B ritish Jo u rn a l o f in d u stria l M edicine 1991;48:173-178 173 M ortality and incidence of cancer at four factories making phenoxy herbicides NOTICE j D avid Coggon, Brian Pannen, Paul W inter THIS MATERIAL MAY BE PR0TECTE9 ETY COPYRIGHT LAW TITLE 17 U.S. C00E Abstract users, and those eating contaminated foods. Judge To assess the possible carcinogenicity o f phen ments about the toxicity of new compounds in man oxy herbicides and related chlorophenols and dioxins, the International Agency for Research on Cancer is coordinating an international collaborative study of workers exposed to these are usually based on extrapolation from laboratory experiments in vitro and in animals. Many pesticides have now been in use long enough, however, that it is possible to assess even their chronic effects more compounds in their production or use. Four directly. Such assessment is important because B ritish cohorts o f chem ical manufacturers laboratory investigation may not always reliably which have been recruited to the survey are predict toxicity in man. described. They comprise a total o f 2239 men One group of compounds that have attracted em ployed during 1963-85. These subjects were particular attention are the phenoxy herbicides (for traced to 31 Decem ber 1987 through the example, 2,4,5-trichlorophenoxyacetic acid (2,4,5- National Health Service Central Register and T), 2,4-dichlorophenoxyacetic acid (2,4-D), the National Insurance Index, and their m or 2 methyl-4 chlorophenoxyacetic acid (MCPA)). Dis tality compared with that in the national covered in the 1940s, these chemicals have found population. Two deaths were from non- extensive worldwide use in agriculture and forestry, Hodgkin's lymphoma with 0-87 expected. Both as well as being sold on a smaller scale for domestic deaths occurred more than 10 years after first application in gardens. Initial case-control studies in exposure to phenoxy compounds. One further Sweden suggested that exposure to phenoxy com non-Hodgkin's lymphoma was registered in a pounds and structurally related chlorophenols might living subject with probable exposure to phen carry an increased risk of soft tissue sarcoma12 and oxy compounds. No cases of soft tissue sarcoma lymphoma.' This idea was supported by the findings or Hodgkin's disease were recorded. A non of four cohort studies of chemical manufacturers in significant excess o f lung cancer (19 deaths the United States.4"7 Subsequent investigations, observed, 14-2 expected) is probably attribut however, have been less conclusive.*"22Several have able to chance or a confounding effect of shown associations between the manufacture or use smoking. In one cohort only there was of phenoxy compounds and soft tissue sarcoma or increased m ortality from circulatory disease lymphoma, but risk estimate's have been smaller than (34 deaths observed, 20-4 expected). A nested in the earlier studies and usually not statistically case-control study did not point to any significant. occupational cause for this excess, but further The statistical uncertainty surrounding small evaluation will be needed during continued increases in risk for rare diseases presents a problem follow up. in evaluation. To help resolve this issue, the Inter national Agency for Research on Cancer (IARC) has The regulation of pesticides requires that the utility established an international collaborative survey of of products be balanced against any risks to the workers exposed to phenoxy acids and related com environment and to the health of manufacturers, pounds.25The study includes cohorts from six Brit ish companies. Data on two have already been published.1424Here we describe the other four British workforces in the IARC survey, and report their mortality and cancer incidence. The findings are > M R C E n v iro n m e n ta l E pidem iology U n it, U n iv er- relevant not only to the assessment of phenoxy I sity of Southam pton, S outham pton G eneral Hospi ta l, S o u th am p to n S 0 9 4XY D Coggon, B Pannen, P Winter compounds but also to other chemicals that have been manufactured and formulated at the same factories. '**- , f r '41 'fcl' 1 174 Coggon, Parnell, W inter Toiie 1 D efinition o f cohort sa Factory Phenoxy herbicides and chlorophenols produced and form ulated (unless otherwise staled, dates are fo r both production and form ulation) O ther mam products ^D efinition of cohort Number of men analysed Number of traced A 2,4,5-T 1968-78 Picric, add 2.4- D and 2,4-DP 1954- Dinitro-o-butyl phenol 2.4- DB 1965- Diaitxo-o-cresol MCPA and MCPP 1954- Simiaxte MCPB 1970- Aminotriazole PCPA and PAA (produced only) 1969- Oxynils All manual employees during April 1975Octobcr 1985 1104 B 2,4,5-T (formulated only) 1970-74 Dithiocufeamates All weeklypaid employees 271 2,4-D, 2,4-DP and 2,4-DB 1969- Organophosphorus compound* during March 1969- MCPA and MCPP 1969- Carbamates Novembcr 1985 MCPB formulated 1969- Disocap produced 1975 - Toluidine compounds Urea herbicides Imidazole compounds Phthaizmide compounds C 2,4,5-T (formulated only) 1959-81 Amuopbyliine 2,4,-D (formulated only) 1959-81 Metronidazole MCPB 1956- Sulpbonas&ides PBA (produced only) 1958-75 Oxynils Diaocap Asulam Sodamide Diflufrnican (1) All process workos on tbe phenoxy plant during January 1963--December 1984 (2) All formulators and packers during January 1982Decanber 1984 (3) All maintenance workers during July 1967December 1984 345 D 2.4.52.4- DT (formulated 1949 - only) 1960-79 Metallic soaps Plaiddser eaten 2.4- DP 1955- Naphthenic add MCPA 1951 - Alkyl phenols MCPP produced 1955- Phthalate esters formulaied 1965- 2.4.6-TCP (produced only) 1983- All weekly paid employees during April 1969Dccember 1985 519 1062 261 343 503 2,4,5-T 2,4,5-Trichlorophenoxyacetic add, 2,4-D 2,4-dichlorophenoxyaceric add, 2,4-DP 2,4-dichlorophenoxypropionic dd, 2,4-DB2,4dichiorophenoxybutyric add, MCPA* 2 mcihyl-4 chlorophotoxyacetie add, MCPP --2 methyl-4 chlorophenoxpropionic add, MCPB--2 methyl-4 chloropbenoxyburyric add, PCPA--parachloropbenoxyacctic add, PAA--pbenoryacenc add, PBA pheooxybutyric add, 2,4,6-TCP 2,4,6crichlorophenol. tAs only one woman ma these criteria, tbe study was restricted to men. M ethod Subjects worked at four factories each of which manufactured and formulated a range of chemicals including phenoxy herbicides (table 1). The com pound 2,4,5-T was produced at factory A during 1968-78, but at the other factories it was only formulated. Manufacturing processes were similar at all four factories. The relevant substituted phenol was reacted with monochloroacetic acid to produce phenoxyaceric compounds, with a-chloropropionic acid to make phenoxypropionic compounds, and with y-butyrolactone to produce phenoxyburyric compounds. The 2,4,6-trichlorophenol was synthe sised at factory D by chlorination of dichlorophenol. Table 1 sets out the criteria for entry to the cohort. Scope for recruitment was limited by the availability of complete records from which subjects could be identified. At factories A, B, and D information was obtained from personnel or wages files. At factory C process and maintenance workers were identified from bound registers kept by shift foremen, and formulators and packers from personnel records. For each member of the cohort we abstracted (as far as they were available) the name, date of birth, address, national insurance number, and job history. Job histories were used to classify subjects accord ing to their potential exposure to phenoxy com pounds and chlorophenols. At factories A and D records were sufficiently detailed to distinguish jobs that entailed work with these chemicals. The few subjects who worked only in ,non-phenoxy plants were considered to have only "background" exposure. At factory C process operators were iden tified from the shift register on the phenoxy plant, and thus are known to have worked with phenoxy compounds. Maintenance workers and formulators and packers were also considered to be exposed, although a few may not have come into contact with the compounds if they only worked in the job for a short period. The employment records at Factory B 2549 $0 II I M oriaiity and incidence o f cancer al fo u r factories making phenoxy herbicides 175 T able 2 O bserved a n d expected m o ria iity by cause: a ll subjects Cause o f death Deaths observed A nalysa based on national rases D eaths expected SM R 95 C l Expected numbers locally adjusted Deaths expected SM R 95 C l All causes Circulatory disease Respiratory disease Injury and poisoning All cancer Cancer of lung Soft tissue sarcoma Hodgkin's disease Non-Hodgkin's lymphoma 152 74 8 19 37 19 0 0 2 136-22 63 76 11-78 12-27 36-84 14-15 0-18 0-43 0-87 112 116 68 155 100 134 0 0 229 94-131 91-146 29-134 93-242 71-138 81-210 0-2087 0-855 28-827 134-73 63-94 11-74 11-06 3666 14-21 0-18 0-38 0-73 113 116 68 172 101 134 0 0 272 96-132 91-145 29-134 103-268 71-139 80-209 0-2058 0-976 33--983 Deaths were also observed from cancer of mouth (1), oesophagus (1), stomach (2), small intestine (1), large intestine (2), rectum (2), bowel not further specified (1), pancreas (2), larynx (1), bone (1), tesus (1), and bladder (1). did not distinguish between work on different processes, and individual exposures therefore could not be assigned with confidence. Management estimated that approximately 50% of employees would have worked with phenoxy compounds during campaign periods (January-May), but all staff were likely to walk through the production areas on occasions. No environmental or personal monitoring for phenoxy compounds, chlorophenols, or con taminant dioxins had been carried out at any of the factories. Subjects were traced through the National Health Service Central Register and National Insurance Index up to 31 December 1987. For those who had died we obtained a copy of the death certificate with the underlying cause of death coded to the ninth revision of the International Classification of Dis eases. We were also notified of any cancers registered among living members of the cohort. Mortality ratios standardised for age (in five year bands), sex, and five year calendar period of death were calculated by the person-years method with rates for England and Wales as standard. In some analyses a second set of mortality ratios was derived with expected numbers of deaths for each factory adjusted in proportion to standardised mortality ratios (SMRs) during 1974-85 for the local authority area in which the factory was situated. Confidence intervals for mortality ratios were based on the Poisson distribution. Results A total of 2256 men satisfied the criteria for entry to the cohort, but 17 had to be excluded from the analysis because their date of birth was unavailable. Of the remaining 2239 men, 2189 (97-8%) were traced, including 152 who had died and 19 who had emigrated. These 19 were followed up to the date that they left the country, while untraced subjects were considered to be at risk up to their last known date of employment. Table 1 shows the numbers of men traced from each factory. Table 2 shows mortality by cause for the full cohort. The total of deaths observed during the follow up period was a little higher than expected from national rates, and this was due largely to excesses of circulatory disease (SMR = 116,95% Cl 91-146) and of deaths from injury and poisoning (SMR 155, 95% Cl 93-242). Overall cancer mortality was dose to expectation, but there was a small excess of deaths from lung tumours (19 observed v 14-15 expected). Two deaths from nonHodgkin's lymphoma were recorded compared with T able 3 M o rta lity b y fa c to ry fo r selected causes Factory A Cause o f death Deaths Deaths observed expected Ail causes Circulators disease Respiratory disease Injury and poisoning All cancer Cancer of lung Non-Hodgkin's lymphoma 62 34 1 7 12 6 0 44*70 20-42 3-41 4-77 12-26 4-63 0-31 Expected numbers are based on national rates. Factory B Deaths Deaths observed expected 17 11-90 5 5-29 1 1-25 3 1-43 5 2-83 3 0-99 0 0*07 Factory C Deaths Deaths observed expected 22 30-13 12 14-31 0 2-33 3 2-59 6 8-34 4 3-22 1 0-20 Factory D Deaths Deaths observed expected 51 49-50 23 23-75 6 4-79 6 3-48 14 13-42 6 5-30 1 0-29 2550 m XW" .......... .. ....... J-'*~ ----- ^ .v ..--,. - - 176 T<iji/ A /^OTt&lzSy jTQTT! SCls&sd com pounds an d jo r chlorophenoh Cause o f death Grculatory diieaje All cancer Cancer oflung Non-Hodgkin'lymphoma SMRs are based on national rares. Coggon, P arm en , W ittier F actories A , C, a n d D soizk g re a ter than background exposure so p k m o x y Subjectsfollowed up from first exposure above background Deaths observed SM R 59 117 30 102 14 123 2 282 Subjectsfollowed upfrom JOyea n after first exposure above background Deaths observed SM R 31 110 13 80 6 92 2 588 0-87 expected, but there were no deaths from Hodgkin's disease or soft tissue sarcoma. Adjustment for local differences in mortality had little effect on expected numbers. Table 3 summarises mortality patterns by factory. The excesses of lung cancer and of injury and poisoning were spread across all factories, whereas the high rate of circulatory disease was confined to factory A (34 deaths observed v 20-42 expected). With adjustment for local mortality, the expected number of circulatory deaths at factory A rose to 24-49, and the excess fell just short of statistical significance at a 5% level. The two deaths from nonHodgkin's lymphoma occurred at factories C and D. Table 4 shows mortality ratios for subjects at factories A, C, and D with more than background exposure to phenoxy compounds or chlorophenols. Standardised mortality ratios for circulatory disease and all cancers were similar to those for the full cohort, whereas that for lung cancer was rather lower, especially after allowance for a latency of 10 years from first exposure. The two cases of nonHodgkin's lymphoma both occurred more than 10 years after first exposure to levels above back ground-one man had been a packer for 21 years and the other a process operator in phenoxy acid synth esis for one month. Only one further case of non-Hodgkin's lym phoma had been registered among living members of the cohort--a process worker at factory B. There were no registrations of Hodgkin's disease or soft tissue sarcoma. Eight of the 19 deaths from injury and poisoning occurred while the men concerned were still working at the factories under study. Of these, two were due to accidents at work, two to accidents outside work, three to suicide or possible suicide, and one to homicide. To investigate further the excess of circulatory disease at factory A, we carried out a nested casecontrol study. Each of the 34 cases at the factory was matched with four controls who were under follow up at the time that the case died, and whose date of birth was as close as possible to that of the case. Year of birth was matched to within one year for 82% of controls, and the mean year of birth of controls was one year later than that of cases. Associations with having ever worked in various departments were examined by conditional logistic regression for matched sets." Table 5 summarises the findings. No individual department was clearly associated with a risk of circulatory disease. Risk was significantly increased among the aggregate of smaller depart ments (the `other' category in table 5), but detailed examination did not suggest a common underlying factor. D iscu ssio n Although the workforces that we studied were exposed to a multiplicity of chemicals, this only presents a problem of interpretation in relation to positive findings. Any reassurance deriving from Table 5 Risk of circulatory disease at Factory A according to department D epartm ent Oxyntls Nitration products Triazines Engineering Effluent Plant cleaning Other Subjects ever employed in department Cases (tt~ 34) Controls (nm. 3 6 ) 0 16 11 04 4 19 28 25 15 19 Relative risk 0 40 0 0-8 1-0 1-6 6-2 9SV. C l 0-3-640 -- 0-3-2-6 02-4-7 0 3-82 2-3-16-4 2551 M o rta lity and incidence o f cancer at four factories making phenoxy herbicides 177 risks which were nor increased extends to all therefore carried out a nested case-control study to exposures experienced by the cohort. Unfortunately, examine other possible occupational risk factors, but levels of exposure to specific chemicals could not be could find none that would explain the observation. precisely estimated. In particular, no hygiene data The excess could perhaps be due to a combination of were available for phenoxy compounds, for the smoking and other non-occupational causes, but it chlorophenois from which they were made, or for the will require further evaluation during continued dioxins with which they may have been contamin follow up. ated. From descriptions of processes and methods of Despite the limitations imposed by small numbers operation provided by longstanding employees, and the potential difficulties in unravelling the effects however, we estimate that exposures during the early of multiple exposures, it is important that studies pan of the study period would generally have been such as this are carried out. They provide an essential higher than more recently. Thus, any risks from audit of the extrapolation from laboratory data on current working practices at the factories are likely to which most decisions for the regulation of pesticides be lower than those in the workers studied. are based. We will continue to follow up these No soft tissue sarcomas or Hodgkin's lymphomas workforces and review their mortality and cancer were recorded in the study cohon during the period incidence at intervals. of follow up. There were, however, two deaths from non-Hodgkin's lymphoma compared with 0-87 We thank the staff of the NHS Central Register and expected, and one further case was registered in a the National Insurance Index for their assistance in subject who was still alive. Expected numbers of tracing subjects and Rosemarie Kirby for her help incident cancers could not be reliably estimated with the computing. The study was supported by a because the completeness of cancer registration in grant from the International Agency for Research on Britain has varied between regions and over time, but Cancer. our findings accord with those of most previous studies in suggesting that any risk of soft rissue Requests for reprints to: Dr D Coggon. sarcoma or lymphoma from occupational contact with phenoxy compounds is small.*"3 A more precise estimate of the risk of these rare tumours will be possible from analysis of the full IARC survey with its much larger study population. The largest excess of cancer found was for lung tumours (19 deaths observed v 14-2 expected), and this derived from all four factories. Most of the deaths occurred, however, less than 10 years after first exposure to phenoxy compounds or in subjects with only background exposure. After allowance for a latency of 10 years from first exposure, the increased risk disappeared (table 4). This and the absence of a comparable association with lung cancer in most other cohort studies of phenoxy workers57' " " * suggests that phenoxy compounds are unlikely to be responsible for the excess. A more likely explanation is chance or a confounding effect of smoking. Data on the smoking habits of cohort members were not available. The only diagnostic category for which we found a clear increase in risk was circulatory disease, and this was confined to factory A where 34 deaths were observed v 24-5 expected (after adjustment for local patterns of mortality). The finding is particularly remarkable since occupational cohorts usually exhibit a deficit of cardiovascular deaths because of the healthy worker effect. The limitation of the excess to one factory and the absence of similar associations in other cohorts of phenoxy workers'TM " * argue against a hazard from the phenoxy process, but it was possible that some other aspect of work at factory A might be responsible. We 1 Hardell L, Sandsrrom A. Case-control study, soft tissue sar comas and exposure to phenoxyacetic adds or chlorophenois. flr J Cower 1979-.39-.711-7. 2 Eriksson M, Hardell L, Berg NO, Mller T, Axelson 0. Soft tissue sarcomas and exposure to chemical substances: a casereferent study. Br J Ind M ed 198138:27-33. 3 Hardell L, Eriksson M, Lenner P, Lundgren E. Malignant lymphoma and exposure to chemicals, especially organic solvents, chlorophenois and phenoxy adds: a case-control study. Br J Cancer 1981;43:169-76. 4 Honchar PA, Halperin WE. 2,4,5-T, trichlorophenol and soft tissue sarcomas. Lancet 1981d:268-9. 5 Zack JA, Suskind RR. The mortality experience of workers exposed to tetracblorodibcnzodioxin in a trichlorophenol process aeddem. J Occup M ed 1980;22:11-4. 6 Cook RR, Townsend JC, Ort G, Silverstdn LG. Mortality experience of employees exposed to 2,3,7,8-tetiachlorodibenzo-p-dioxin (TCDD). J Occup M ed 1980;22:530-2. 7 On MG, Holder BB, Olson RD. A mortality analysis of employees engaged in the manufacture of 2,4,5-trichlorophenoxyacetic add. J Occup M ed 1980;22:47-50. 8 Riihimaki V, Asp S, Hemberg S- Mortality of 2,4-dichlorophenoxyacenc add and 2,4,5-trichlorophenoxyaceric add berbidde applicators in F inland Scand J Work E m m et Health 19824:37-42. 9 Lathrop GD, Moynahan PM, Albanese RA, Wolfe WH. An epidemiologic investigation o f health effects in airforce personnel following exposure to herbicides: baseline m ortality study results. BrooksAir Force Base, Texas: United States Air Force School ofAerospace Medicine, 1983. 10 Greenwald P, Kovasznay B, Collins DN, Themault G. Sar comas of soft tissues after Vietnam service. J Nazi Cancer Inst 1984;73:1107-9. 11 Smith AH, Pearce NE, Fisher DO, Giles HJ, Teague CA, Howard JK. Soft tissue sarcoma and exposure to phenoxy herbiddes and chlorophenois in New Zealand. J N azi Cower Inst 1984;73:1111-7. 12 Royal Commission on the Use and Effects o f Chemical Agents on Australian Personnel in Vietnam. P inal report July 1985. Vol4. Canberra: Australian Government Publishing Service, 1983. 13 Lynge E. Afollow-up study of cancer incidence among workers in manufacture of phenoxy herbiddes in Denmark. Br ] Cancer 1985;32:259-70. 2552 178 Cofgon, Parmet:, Winter 4 Csggon D, Pxnnen B, Wimer PD, Acbesoo ED, Boniall J. Morality of worker exposed to i-mcihyi-v-ehioropbenoxyecede add. Standi J W ork Environ H taith 1986; 12:448-54. 15 Hoar SK, Blair A, Hoboes FF, et aL Agricultunl herbicide use and risk of lymphoma and toft tissue sarcoma. JA M A 1986;2S4:1141-7. 16 Pearce NE, Smith AH, Howard JK, Sheppard RA, Giles HJ, Teague CA. Non-Hodgkin's lymphoma and exposure to phenoxy herbicides, chlotophenols, fencing work, and meat works employment: a case-control study. B r J Ind M id 1986;43:75-83. 17 Wood JS, Poliasar L, Severson RK, Heuser LS, Kuixnder BG. Soft tissue sarcoma and non-Hodgkiri't lymphoma in relation to phenoxy herbicide and chlorinated,phenol exposure in western Washington. J N a tl Cancer irai 1987;78:899-910. 18 Vends P, Terrarini B, Ciccone G, et ai. Phenoxy berbiddes and soft tissue sarcomas in female rice weeders: A populationbased case-referent study. Sta n d J W ork Environ H taith 1987;13:9-17. 19 On MG, Olson RA, Cook RR, Bond GG. Cohort mortality study of chemical workers with potential exposure to the higher chlorinated dioxins. J Oeatp M id 1987;29:422-9. 20 Bond GG, Wetteistroem NH, Roush GJ, McLaren EA, Lipps TE, Cook RR. Cause spedfic morality among employees engaged in the manufacture, formulation, or packagingof2,4 dichlorophenoxyacetic add and related salts. Br J ind M id 1988;4S:98-!05. 11 Perason B, Dahlander A, Fredrikason M, Brage HN, Ohison CG, Axelson O. Malignant lymphomas and occupational exposures. Br J Ind M id 1989;43:516-20. 22 ErikssonM, Hardell L,Adami HO. Exposuretodioxinsas arisk factor for soft tissuesarcoma: apopulation-based case-control study. J N a tl Cancer irai 1990;82:486-90. 23 Johnson ES, Winkelmaim R, L'Abbe RA, at of. Phenoxy add herbiddes and contaminants: Description ofthe 1ARCinter national register ofworkers. Am J hid M ed 1990;18:39-45. 24 Bishop CM, Jones AH. Non-Hodgkinslymphomaofthescalp in workers exposed to dioxins. Lanctt 1981l:369. 25 Breslow NE, Day NE. Statistical methods in cancer research. Vo! 1. The analysis o f case-control audits. Lyon: International Agency for Research on Cancer, 1980:248-79. Accepted 1October 1990 Correspondence and editorials The British Journal of industrial Medicine wel comes correspondence relating 10 any of the material appearing in the journal. Results from preliminary or small scale studies may also be published in the correspondence column if this seems appropriate. Letters should be not more than 500 words in length and contain a minimum of references. Tables and figures should be kept to an absolute minimum. Letters are accepted on the understanding that they may be subject to editorial revision and shortening. The journal now also publishes editorials which are normally specially commissioned. The Editor welcomes suggestions regarding suitable topics; those wishing to submit an editorial, how ever, should do so only after discussion with the Editor. 2553 o-afcW 2554 Poison i ckyard By Kathyrne V . Sagan node disorder that usually affects Asian male children. In the opinion of the hospital doctor, the disease could have been caused by chemicals in ix years ago Barbara and the environment Barbara is doubtful that Kelly, who Greg Marshall* of Sarasota, is blond and fair, actually had the disease. But she Florida, felt pressured by their does think her child was poisoned by pesticides. . neighbors to improve the look of Most of Kelly's symptoms--the breathing difficul their property. "We didn't have ties, skin irritations and bums, swelling, loss ofweight a nice lawn, and everybody else and appetite, headaches, muscle aches and fever-- did," says Barbara. The man are considered signs of poisoning by various pesti across the street suggested the cides, says Bettina Francis, PLD., a toxicologist at lawn-care service ChemLawn. the Institute for Environmental Studies at the Univer"We hired them, and for a while we had the best-looking lawn on the block." "Fo r the price of a green lawn, we are poisoning our What they didn't know was that their children," says the mother of a sick child. Public Citizen, 2-year-old daughter Kelly's* health would be jeopardized. Kelly ran barefoot a consum er group based in Washington, D .C., recently onto the grass one hour after a lawn found that 12 of the most commonly used lawn-care treatment was applied. The applicator had told them their yard would be safe by pesticides are suspected human carcinogens. then, but within a week Kelly developed respiratory sity of Illinois, Urbana-Champaign. According to a 1989 problems, a nasty rash over most of her body, had a report by Public Citizen, a Washington, D.C.-based con high temperature, and her urine turned dark brown. sumer group, 36 of the 40 most frequently used lawnHer pediatrician prescribed antibiotics, but the tod care pesticides cause skin irritations, and 20 cause dler's symptoms got worse--her hands and feet short-term damage to the central nervous system. swelled to twice their size, blistered and peeled, and For the Marshalls and others like them, the subur her lips turned black and bled. She also had bad head ban dream of a well-manicured lawn is becoming a aches and muscle aches, lost weight and her appetite. suburban nightmare. Across the country serious Two weeks later the Marshalls took Kelly to All health problems caused by pesticides are affecting Children's Hospital in S t Petersburg, where she was homeowners and their children, gardeners, golfers diagnosed as having Kawasaki disease--a rare lymph- and other outdoor sports enthusiasts. And even though the Government is aware of the (Continued) K athym e V. Sagan is a F amily Circle editor-at-large. *Nomes have been changed to protect the privacy of the chid. 4/2/91 Fam ily Circi 59 2555 D .A(p 5 ^ ckyard V still have to watch her," her mother says. "She is prone to headaches and has a 40% permanent hearing loss in her right ear, which was caused by the high fevers she suffered-when she was poisoned." In 1986 the Marshalls joined about 20 other plaintiffs (alleging a wide range of illnesses--including nausea, vomiting, rashes, high fever, impairment of muscular coordination and respiratory dis tress) in bringing a class-action suit against ChemLawn Services Corporation, but the court dismissed the suit because the symptoms were too diverse to meet the requirements for class-action litigation. Says Barbara to day, "We have the crummiest lawn on our block again, but when our neighbors saw what happened to Kelly, they canceled their ChemLawn service too." The Marshalls are not the only family to pay a high price for a greener lawn. Barry andJackie Veysey believe expo sure to pesticides may have contributed to the death of their third child, Matthew. When Barry was turf master at the Manatee County, Florida, Department of Parks and Recreation, he sprayed the county ballparks and school yards with arsenic-based pesticides, chemicals that can cause nerve damage, and 2,4-D--a suspected carcinogen and the most frequently used lawn-care herbicide. Barry knew the chemicals were dangerous and urged county offi cials to provide him with proper safety gear and to allow him to post signs and to dose facilities after spraying. When he met resistance, he started keeping records of what he sprayed and also of any faulty equipment he had to use. Jackie, pregnant with their second child at the time of Barry's promotion to turf master, gave birth to a healthy daughter that summer. The followingJanuary she became pregnant again. Short Sharon Malhotra, 3 6 , was diagnosed with ly after this, Barry pesticide poisoning four years ago. Her started to feel ilL He had been acddentally neurologist suggested that she wear a gas doused with pestirides a few times by a dam m ask whenever she thought she might be aged hose and had once exposed to lawn-care chem icals. been sprayed in the eye. His fiulike symp The Malhotras ofPennsylvania havepersonally experienced, theperils ofpesticides. tom s p ersisted for more than sue weeks dangers of commonly used pesticides, very little is actual and were accompanied by chronic musde aches and head ly being done to protect the public. aches. He finally went to the doctor that spring. (Early "Lawn-care companies have perpetrated a massive con symptoms of poisoning by some pesticides are frequently job on the American people. Let's fight the deadly dande mistaken forflu.) Although tests showed arsenic in his body, lion, they say, even if it means using deadly toxins," says the levels were apparently not high enough to harm him. Samuel S. Epstein, M.D., professor of occupational and At 34, Jackie's third pregnancy proceeded normally. environmental medicine at the University of Illinois Medi She felt the baby kick, and he had normal head measure cal Center Chicago, School of Public Health. ments. "On the day in October when we went into the Children are especially vulnerable to these chemicals. delivery room we were so excited," she says. "Then, as Kelly Marshall remained bedridden for months, her limbs the delivery progressed, a quiet filled the room and my and neck sometimes so swollen that her parents had to tie whole life changed." Matthew was bom with thanato a sock around her neck to keep her head upright During phoric dwarfism, a severe, fatal type of dwarfism. Most of this time Barbara Marshall learned of two other children his organs were not fully developed. The baby was imme diagnosed with Kawasaki disease whose families had used diately put on a respirator. Jackie got to hold her son only a professional lawn-care service. once before he died 23 hours later. Kelly, now 8, has built up her immune system. "But we The Veyseys' doctor told them that this (Continued) 260 Family C irda */ /vi 2556 Poison in Yo ckyard type of birth defect was so rare that very the Chemical Producers and Distributors Associa few data exist as to its causes. He said some tion, said at a Senate hearing on lawn-care pesti research indicates that a gene mutation cides last spring, "Despite the claims that lawn- seems to be the most likely cause, though care chem icals are `su sp ected human nothing is conclusive. The Veyseys believe carcinogens, ' nothing could be further from the that the chemicals Barry was working with may truth.. . . Most of these products have a long have mutated his sperm, or that the fetus may record of common usage, with a safety record ofno adverse have been exposed in utero each time Jackie laundered health effects. There should be no cause for public concern Barry's uniforms. Many chemicals can cross the placental about the health effects of lawn-care chemicals." barrier and harmfully affect the fetus. Arsenic is toxic to But there is no nationwide reporting of pesticide poi fetuses, and at least six of the pesticides Barry worked soning. Although the American Association of Poison Control Centers estimates that it recorded about 48,000 pesticide exposure-related phone calls in 1989, the orga nization cannot pinpoint the number of calls that were lawn-care related. And as toxicologists point out, such poisoning is frequently misdiagnosed. `T he symptoms of pesticide poisoning mirror other diseases and health prob lem s," says Mark Lapp, Ph.D., a toxicologist and pro fessor of health policy and ethics at the University of Illinois College of Medicine. One of the biggest questions is why only some people-- even within the same family--are affected by exposure. Says Professor Lapp, "No one knows why. There's a strong suspicion that there are genetic differences in the way people break down these chemicals. Another impor tant factor may be body size and route of exposure." Marion Moses, M .D., president of the Pesticide Educa tion Center in San Francisco, has another explanation: "A person's age, the type of chemical involved and the de gree of exposure, among other factors, have more to do with it than genetics," she says. Americans are overdosing their lawns. According to the National Academy of Sciences, homeowners use between 5.3 and 10.6 pounds of pesticide per acre on their lawns-- many times the amount generally used by farmers. As many as 11% of single-family households hire a commer cial applicator, creating a $1.5 billion professional lawn- care industry. But of the 40 pesticides that make up 95% of the lawn-care busi- IB MM* " I feel like a prisoner/' says 12-year-old Kevin Ryan, who loves baseball but, unlike ness, only one, metalaxyl, has been completely tested and other kids his age, can't play the gam e. In reviewed by the EPA for its full range of feet, he seldom can go outdoors, and he health effects. fell ill after posing for this photograph. Sharon Malhotra, 36, a registered nurse Deborah and Kevin Ryan at theirIllinois home, which they must vacate during spraying season. and m other of two, first began in late with--including Aatrex, Baygon and Benlate--are sus spring of 1987 to link her bad headaches with the days her pected to cause birth defects. town-house lawn in suburban Pittsburgh was treated. She "This baby died because of my job," says Barry. Adds was at the town-house pool when she developed a head Jackie, "If this could happen to someone who knows so ache so excruciating that she-had to go home to bed. She much about the dangers of pesticides, what about people became nauseated; her nose, tongue and arms started to who go to the local hardware store, buy a two-pound bag tingle and go numb; her muscles were visibly twitching, and apply it themselves?" and she had trouble speaking. Her husband, Narinder, a The chemical and lawn-care industries consider such doctor, suggested she see a neurologist. The specialist concerns--over what they say are minuscule amounts of found no major neurologic disorder, but he suggested that toxic substances--needless. WarrenE. Stickle, president of Sharon might be reacting to lawn chemicals. (Continued) 62 Family Circi* 4/2/91 2557 Poison in Yo ckyard One week later the trees near the Malho- used were "practically nontoxic," were regis tras' town house were treated for an insect tered for use by the EPA and were not harmful problem. Sharon again developed a severe to humans or pets, adding that a child "would headache and also had trouble breathing. She have to ingest the amount of pesticides found in looked outside and could see the pesticide almost 10 cupfuls of treated lawn clippings to dripping off a tree directly in front of her win equal the toxicity of one baby aspirin." dow. A few days later the chemical odor was The Malhotras assumed that EPA registration meant still strong, so she went out and naively nosed the tree that the products had been tested and were therefore down with water. As she stood under the tree to water safe. Dr. Malhotra was shocked to learn later that al the flowers, the chemicals dripped down on her. Within though some of the pesticides Sharon was exposed to may minutes her left arm went numb; then her peripheral vi- cause temporary nerve damage, there are surprisingly ________________ sion became blurry and her stomach few EPA studies on the chronic or long-term effects of cramped so severely that she was exposure to these chemicals. bent over in pain. Organophosphates, the class of toxic chemicals that From his wife's symptoms Dr. affected Kelly, Barry and Sharon, can cause nerve dam Malhotra suspected her levels of an age. They are "first cousins" to the chemicals Sarin and enzyme called cholinesterase were Tabun, developed by the Germans as weapons during World War II (and cur The Navy (fid a thorough investigation of Lieutenant rently stockpiled in Iraq's chemical weap Prior's death. An autopsy showed that Prior died from ons arsenal), and are one of the most widely toxic epidermal necrolysis, a severe skin reaction, used groups of pesti the result of exposure to a fungicide used on the golf cides today. B etty G erstley, M.D., a course in Virginia where he had frequently played. Philadelphia internist, says it's possible that Navy Lieutenant GeorgePrior, a casualty ofDaconil at the age of30. exposure to these neu- -rotoxins contributes to diseases of neurologic being affected. (Lower cholinesterase levels indicate tem degeneration, such as Parkinson's, Lou Gehrig's (amyo porary nerve damage--a thumbprint of pesticide poison trophic lateral sclerosis) and Alzheimer's disease. ing by organophosphates, a group of potent neurotoxins.) Like the Marshalls, the Veyseys and the Malhotras Acting on his hunch, Dr. Malhotra called the lawn-care (none of whom consider themselves chemically sensitive), company to ask what chemicals had been applied. The many people assume that the EPA is protecting Ameri company sent him pamphlets stating that the chemicals cans from these toxins, but it is (Continued on page 108) How to Protect Yourself Use organic alternatives whenev er possible and practice "integrated pest management"-- plant diseaseresistant grasses, keep grass height at 3" to A", aerate the lawn regularly and use clippings as fertilizer. When you must, use chemicals only to com bat specific problems. W hen applying pesticides or weed killers yourself, follow all label directions and note the product's level of toxicity. "Caution" signifies the least toxic, "warning" is consid ered more toxic, and "danger" marks the most toxic chemicals. W ear long sleeves, pants, hat, dust mask, and gloves and shoes of the most impermeable material-- rubber is better than leather or canvas. If clothing comes in contact with pesticides, change immediately and wash it separately. Wash gloves thoroughly before removing them. Keep children and pets aw ay from treated areas for 24 hours if possi ble. Store products out of reach. When your lawn or your neigh bor's lawn is being treated, close house and car windows, turn off airconditioners and remove or cover lawn furniture, toys, swimming pools, fish ponds, hoses, pet bowls and bird feeders. Before choosing a lawn-care ser vice, check to see if the company is licensed by your state and ask what specific training employees have. If treatment is recommended, ask what specific problems exist and w hat chemical the company plans to use before you agree to treatment. Stand upwind when pesticides are being a p plied ; do not a p p ly in winds of over 10 miles per hour. Dry or pellet-form pesticide is not necessarily safer than liquid as it can leak vapors into the air. Some dry fer tilizers also contain pesticides. For more inform ation, call the EPA's National Pesticide Telecom munications Network at 1-800-858PEST. For "The Lawn C are Packet" send $2 to; The National Coalition Against the Misuse of Pesticides, Dept. FC, 701 E St., S.E., Suite 200, Washington, D C 20003. -- Elizabeth Lyon 4/2/91 Family Circi 63 2558 PesticideScandal continuedfrom page 63 not. At least 32 of the most commonly used pesticides were registered prior to 1984, the year stricter testing guide lines were established. These pesticides must all now be reassessed, a process that will take into the 21st century to complete, why the delay? Mismanage ment, lack of funds, low priority, indus try interference--all have been suggested, by people both within the Government and outside it Meanwhile, at garden centers and hardware stores, many of these chemicals are readily available, sharing shelf space with seed packets and watering cans. "There's reason for concern be cause millions of children are being ex posed to toxic chemicals, notjust inlawn products but in pest strips and any num ber of common household products," says Dr. Moses. "If there were a little more awareness and a lot more truth in labeling, then people wouldn't bring these chemicals into their homes." By law only "active" ingredients in pesticides must be listed on a label, al though "inactive" ingredients may in clude such cancer-causing chemicals as dioxin, found in DacthaL EPA testing fo cuses primarily on ingestion of "active" ingredients. And according to Victor J. Kimm, the EPA's deputy assistant ad ministrator for pesticides and toxic sub stances, in his testimony at last spring's Senate hearing on lawn care, the EPA has no way of assessing the amount of lawn-care chemicals we inhale or absorb through our skin---the most frequent pathways of exposure. EPA testing also doesn't take into account the cumulative effect of expo sure to chemicals. By the time a child is 6years old, his brain cells are fullydevel oped. Even if those cells are damaged, the brain does not renew itself (as skin does, for example). The EPA also does not factor in the synergistic effect one chemical may have on another--the way ammonia interacts with bleach to form dangerous chloramine gas, for instance. Andfew studies have been conducted on the effects of chronic, long-term, lowdose exposure to a chemical. Unlike the Consumer Product Safety Commission, which relies primarily on its own testing to protect Americans from unsafe products, the EPA relies on industry samples and industry test ing. It merely reviews the data and test results provided by the manufacturer and forms conclusions. "If a chemical company wanted to, they could start with a desired conclusion and skew the 108 Family Circle 4/2/91 data, and the EPA would never know," plied is sporadic at best; the Golf says Dwight Welch, an entomologist in Course Superintendents Association of the EPA's Office of Pesticide Pro America estimates that only about 20 grams. Welch recently did a random states require it Some others, like sampling of the files of 15 pesticides Florida, require residential lawn-care and found 13 without proper reviews. companies to post warning signs after spraying, but do not require golf America's quest for the perfect playing field goes beyond our backyards. On sunny days peo ple swarm to grassy expanses at courses to follow the same rule. Golf is not the only sport to rely on chemically treated grass. For baseball fan Kevin Ryan of Arlington Heights, local parks, baseball diamonds and golIfl-linois, playing on a Little League team course fairways. is a dream that will never come true. Navy Lieutenant George Prior was As a toddler inthe late 1970's, Kevin an avid golfer. He had played several played in a sandbox that bordered the times on the Army Navy Country Club next-door neighbor's property, and he golf course inArlington, Virginia, inthe had free run of the neighbor's lawn, weeks before his sudden death. Nor which was regularly sprayed with pes mally in perfect health, the 30-year-old ticides. Like most people back then, officer did not feel very well during this his mother, Deborah, had no idea this period, but he never associated it with could be dangerous. his golfing. Then one Saturday--after Today Kevin, now 12, gets stomach playing a full 18 holes--he abruptly got pains, has trouble remembering things, and feels nauseated, irritable and fa tigued when he is exposed to pesti cides; his arms and legs tingle and go numb. He can't play outdoors with fas friends and can't attend his public school because it routinely uses pesti "I f there were a cides. "I feel like a prisoner in my own home," Kevin says. During the spring little more awareness and fall--peak spraying times--his mother takes him and his younger a n d a lot more truth brother to Colorado, where she be lieves the air is cleaner. in labeling, then Schools and communities often feel no responsibility to notify people of people w ouldn't spraying activities. Five years ago Southboro Elementary School in West bring these chemicals Palm Beach, Florida, was forced to dose for three days when 35 young into their homes. " sters became nauseated after wind blew toxic insectidde fumes from a desperately ill. "George became gro nearby park into the school's air-condi tesquely swollen," says his brother tioning system. Tom. "Enormous blisters appeared on "For the price of a green lawn," says his body. One by one his organs failed, Deborah Ryan, "we are poisoning our his skin sloughed off, and he went children. " Public Citizen recently found blind. The pain was ceaseless, and af that 12 of the most commonly used ter 14 excruciating days, he died." lawn-care pestiddes are suspected hu The Navy did a thorough investiga man carcinogens. One of them--2,4-D tion of Prior's death. An autopsy --is found in about 1,500 products on showed that he had died from toxic epi the market dermal necrolysis, a severe skin reac Unfortunately, children are most at tion, the result of exposure to the risk. According to a report published fungicide Daconil, which had been used by The Journal of Pesticide Reform, on the golf course. . young children's cells divide more rap Prior's is an unusual case. According idly than adults', their organs are not to Jim Snow, a national director of the fully developed, their immune system U.S. Golf Association, no other in is immature for the first two years, and stances ofgolfers beingpoisoned bypes their play habits expose them to more ticides have been recorded. However, chemicals--they're much more likely as toxicologists point out, such poison to tumble in grass and play in dirt than ing, particularly by organophosphates, adults. Neurotoxins (which indude all might not automatically be diagnosed. organophosphates) can cause learning The posting of warning signs on golf problems in children during the critical courses after pesticides have been ap years when they must (Continued) 2559 o putting the public at risk. "We have a very active research and development continuedfrom page 108 department that is constantly looking for new and better ways to treat cus develop motor and social skills, and tomers' lawns," she says. "We're as learn to speak, read and write. much or more concerned about health A National Cancer Institute study risks than the general public or the ac has shown that children in homes tivists. The only difference is we're where pesticides were used both in working through knowledge and doors and out were as much as seven they're working through fear." times more likely than other children to Karen James, a postal worker in develop leukemia. Children whose par Michigan, successfully sued Chem ents worked with pesticides were also Lawn in 1988. Karen was delivering at a higher than average risk. mail in her jeep along a rural route when her access to a mailbox was F ertilizers, frequently thought to be harmless, can bum the skin severely. In the summer of 1986, two hours after a service called blocked by a ChemLawn truck. She got out of her jeep and walked past the truck to deliver the mail by hand when a hose on the truck ruptured, drench Mister Lawn Care had treated hering her with liquid. The employee who lawn, Robin Dudek of Hamburg, New was applying the chemicals said the York, pulled her garden hose from the tank contained only fertilizers. But Ka lawn onto her back deck, turned on the ren suddenly felt nauseated and her water and placed the hose in the inflat able pool with her small daughters, Amanda, 3, and Kristen, 2. Amanda started drinking from the hose but screamed that the water was burning her. Then Kristen began to scream too. Robin took the children inside; she One fle a repellent's noticed bum marks on both of them and smelled chemicals on Amanda's p a ck a g in g w arn s o f breath. She immediately called her pe diatrician, who instructed her to bathe the p ro d u ct's danger the girls. But by the next morning, Amanda and Kristen woke up with fe to pregn an t dogs but ver, swollen eyes and blisters the size of grape clusters on their arms and neck. says nothing about Robin took them to the emergency room at The Children's Hospital of Buffalo, its p o te n tia l danger where they were treated for first- and second-degree bums. It was about a to p regn an t women. month before the girls fully recovered. "The EPA should be called die 7PA-- eyes and skin began to bum. the Industry Protection Agency," When she remained so sick that she charges Jay Feldman, national coordi couldn't return to work, Karen strong nator of the National Coalition Against ly suspected there was a link between the Misuse of Pesticides. "The chemi her illness and the incident with the cal industry is extremely powerful and truck. She was vomiting and had diar wraps the EPA in red tape." rhea, felt very fatigued, and her vision New York State Attorney General was temporarily reduced in one eye. Robert Abrams, who took ChemLawn Her doctor called ChemLawn to find to court for maidng false safety claims out what chemicals had been used and and won the state a $100,000 settle was told no pesticides were involved. ment in 1990, points out, "An EPA It was only after Karen's body tissue registration number on a package is not was tested and the presence of the ac a guarantee of safety; the registration tive ingredient of the organophosphate process is a balancing act of health Dursban was found that ChemLawn risks versus economic benefits, not a admitted the truck's tank had contained safety determination." In the case of this pesticide. lawn-care chemicals, "economic bene "There was some confusion about fit" translates into greener, bug-free what was in the tank. We had to find lawns, increased property values, bet the records," explains ChemLawn's ter business for country clubs, lawn- Strohmaier. Nevertheless, Karen, care sendees and chemical companies. who was out of work for six weeks, ChemLawn spokesperson Deb sued; a jury awarded her $1 million. Strohmaier feels the company is not Many other cases against lawn-care 110 Family Circle 4/2/91 companies and manufacturers have been settled out of court. Fre quently, the settlement restrains the plaintiff fromtalking about the incident The lawn-care industry has few reg ulations and almost no enforcement No standard licensing requirements ex ist and training varies from state to state. Once licensed, an applicator may oversee his own business and hire other applicators, tnese workers need not be licensed; they are required only to be registered, allowing them to go off on their own to treat property. In Florida, for example, only 4,000 of the 30,000 registered applicators are licensed. Despite the risks, most homeowners aren't willing to give up a green, bug-free lawn. But doit-yourselfers need to take spe cial precautions. (See "How to Protect Yourself," page 63.) The labels on store-bought pesticides are often in complete or misleading. Although Federal law requires lawncare products to carry warning labels, some of these warnings are written in doublespeak that only doctors can un derstand. Or a warning may list possi ble symptoms of exposure--like blurred vision, lightheadedness and sweating--but fail to mention that con tinued exposure to the product mayre sult in permanent nerve damage. Packaging may also imply that a chemical is harmless by displaying a picture of a man dressed in shorts ap plying the product Others state the danger to animals but not to people. The flea repellent carbary1, for exam ple, warns of danger to pregnant dogs but says nothing about its potential danger to pregnant women. The law does prohibit manufacturers from making safety claims on labels about pesticides, including the use of such descriptions as "safe," "nonpoisonous," "noninjurious," "harmless" and "nontoxic to humans or pets"-- with or without a qualifying phrase like "when used as directed." Yet lawn-care companies often do make false advertising claims or give false verbal reassurances. An investi gation by the U.S. General Accounting Office (GAO) revealed that various companies made the following claims over the phone to GAO investigators posing as potential clients: "Our prod ucts are practically nontoxic--no one gets sick"; "All of our products are le gal and registered at EPA as practically nontoxic''; and "The only way to be affected by 2,4-D would be to lie in it for a few days." The GAO has taken (Continued) 2560 PesticideScandal continuedfrom page 110 both the EPA and the Federal Trade Commission (FTC) to task for passing the buck on enforcement, saying, "Neither agency is acting against safe ty claims by pesticide applicators." But even when the EPA bans a pes ticide, industry doesn't give up. Manu facturers will often appeal the decision in court. In the meantime, the product stays on the market. The EPA's recent ban on the use of the insecticide diazinon on golf courses and sod farms is a typical case. Diazinon has been respon sible for nearly 100 reports of bird kills (up to as many as 800 birds at a time) across the country. However, the ban was delayed when the chemical's major manufacturer, Ciba-Geigy Corpora tion, appealed. Although the EPA's ban was finally upheld, diazinon is still legal for use on home lawns. The EPA's re view of studies on diazinon remains in complete. When the EPA moves to ban a pesti cide, it may take two to eight years before products are off the shelves. Ironically, one of the EPA's own book lets, "Lawn Care for Your Home," published by EPA Region 5 in Chicago, 18833113 On Ovr Cover O raaa w icker chair. Portico, 67 Wooster St., New York, NY 10012. Cardvray fa b ric for rabbit, Cone (available at local fabric stores). Silkflaw ar (availablethroughde signers), Untied States Flower Company, 131 W. 38th St., New York, NY 10001. Celebrations (S aga 3 4 ) f a w a v a r d ia a e r ta b la , Pierre Deux Antiques. O ab lat, Samuel Saidian & Sons. M atzah y la ta , Thaxton & Co. D o t to r i p h o to t Tabla, Pierre Deux Antiques. Caka p ia ta and ta a p a t, Thaxton & Co. A atiq ae fab ric, Samuel Saidian & Sons. ADDRESSES: Pierre Deux Antiques, 369 Bleecker St., New York, NY10014. Samuel Saidian & Sons, 1050 SecondAve., Gallery 45, New York, NY 10022. Thaxton & Co., 780 Madison Ave., New York, NY 10028. Spring Fever (Rapa 45) U r ic fortabledoth(CountryFancy in Wedgewood), Waoerfy, 1-800423-5881. Rites of Spring (Rapea 6 6 -47) Ora a a wkfcar lava eeat, Portico. SHk Hewer* on basket. United makes false safety claims. It states, "Look for the EPA registration number when buying a chemical product. This is your assurance that the product has been reviewed by EPA and is safe and effective when used as directed." But reforms may be on the horizon. As this article goes to press, the EPA's Office of Pesticides and Toxic Sub stances is undergoing an internal inves tigation by the agency s inspector general. And citizens' groups like the National Coalition Against the Misuse of Pesticides are working to make peo ple aware of the dangers of pesticides inthe hope that knowledge will prevent future health problems. For some people--like Lieut. George Prior and young Matthew Vey- sey--knowledge didn't come soon enough. Had the right information been available, these and other tragedies might have been averted. But as Debo rah Ryan has so often sadly remarked about her son Kevin's exposure, "Who knew?" editor'* motmi What are your experi ences with lawn-care companies or pesticides you have purchased for home use? We'd like to know. Please write to: Pesticides, FC, 110 Fifth Ave., New York, NY 10011. States Flower Company (available through designers). Coal ccatt phie paa (used on basket), Stanley-Parker. Caady ap p i, E. J. Brach Corp. Catered wo adee app, Unfin ished Business. ^FS^^^MgaO^^Sa WMQM RIM borite ti, a lg id a Hape, Unfinished Busi ness. F latw are, p iak placcar. Pottery Barn. O raaa placca*, h aw ir. Portico. N apkiac, Glentex. Rap, ABC Carpet & Home Store. Table, chain. Evergreen An tiques. Caady, E. J. Brach Corp. D o tto ri p b a fa i Table, Evergreen Antiques. Vaea, place, Pottery Bam. ADDRESSES: ABC Carpet & Home Store, 888 Broadway, New York, NY 10003. E. J. Brach Corporation, 4656 West Kinzie St., Chicago, IL60644. EvergreenAntiques, 120 Spring St., New York, NY 10012. Glentex, 417 Fifth Ave., New York, NY 10016. Por tico. 67 Wooster St, New York, NY 10012. Pottery Bam, 700 Broadway, New York, NY 10003. Unfinished Business, P.0. Box 246, Wingate, NC 28174. United States Flower Company, 131 W. 38th St, New York, NY 10001. Stanley-Parker, 149 Washington St., Worcester, MA 01610. Fashion Fads and Fellies (Rape 73) Dree, Cynthia Rowley, 212-465- 9020. R ana, W. Loh & Associates, 415863-3398. Jew elry, Sharent, 212-6293161. Heelery, Givenchy, 212-764-4630. Shaae, Unisa, 212-935-1033. (Rapa 73) Catcall, Bettina Riedel, 212-2440383. Sw eater, Michael Simon, 212-5759222. --i and. Gtiano, 212-819-0707. Shaae, Keds, 617-491-8800. (Rapa 76) W eb h p chert and ta a k tap , Dana Buchman, 212-703-3346. jacket, Evan Picone, 212-536-9500. Shaae, Terra, 212-245-7070. Barrfap^ Sharent, 212-6293161. H aadhap, Vanessa, 212-563-2220. bracelet, Erwin Pearl, 212-889-7410. Sitting Pretty (Repcc 7S-S2) IBpcavan designed byJoe Biando, Harold Rudin Decorators, and Margaret Ahem, Stylish Home Decorators. (Rape 7S-79) le f t: fabric (Brant Point Stripe #656493 and #656496). RJphf: F A ric (Just Stripes #355241, Country Fair Border #356010), all from Waveriy. (Ra p SO-S1) Lofti Fabric on chair (Linen Check #607265), fabric onottomanandpil low (Woodland Toile #657716), both from Waveriy. M a n , Conso. Sheet, PalaisRoyal. Rhaakat, Pearce Woolen Mills, div. of Woolrich. Cartaiae, Lace Country. Comfort Fabric onchair(Tea Party #656070), waSpaper (AwningStripe #553482), bothfrom Waveriy. to p right: Fabric on ottoman (Sonnet #657094), fabric on chair (Classic Ticking Stripe #605224, Linen Check #607260), fabric for piping and pillow (Classic Ticking #605221), fabric for pillow (Country Linen Plaid #645722), all from Waveriy. Bottom rig h tt Laca on chair, Quaker Lace. Trim, Conso. Mfavar, Lillian Vernon. (Rapa S3) Bottom Jeff: F ^ ric on chair (Sailcloth #346432), fabric for piping (Sail cloth #346430), all from Waveriy. ROaar fabric(green #300262), le a f rachlea (Pony Print #100279), both from UltraSuede. Blue vaea, y e a baw l, Objects. S effaai rightt Wicker heel, Ralph Lauren Home Collection. ADORESSES: Conso, 295 Fifth Ave., New York, NY 10016. Joe Biando, Harold Rudin Decorators, 653 11th Ave., New York, NY 10039. Lace Country, 21 W. 38th St, New York, NY 10018. Lillian Vernon, 510 S. Fulton Ave., Mt. Vernon, NY 10550. Mar garet Ahem, Stylish Home Decorators, 10 Wilson Common, Yaphank, NY 11980. Ob jects, 1049 Madison Ave., New York, NY 10012. Palais Royal, 1725 Broadway St., Charlottesville, VA 22901. Pearce Woolen Mills, div. of Woolrich, Woolrich, PA 17779. Quaker Lace, 1040 Sixth Ave., New York, NY 10018. Ralph Lauren Home Collection, 1185 Sixth Ave., New York, NY 10036. Ul traSuede HP, a div. of Springs Industries, 104 W. 40th St., New York, NY 10018. Waveriy, 1-800-423-5881. Winning Recipes (Rape US) Flatw ara, Oneida, Oneida, NY 13421. Rfch eac, Vaban Ribbons, 225 Fifth Ave., Suite 1121, New York, NY 10010.R 2561 O' 2562 /7 o-a^ HPF-ir-1331 1?:0O rFOr! LSI-! OFFICE TO A C a d DELL & C o n w e l l A T T O R N E Y S AT LAW TE PARK .N HOUSTON CENTER i3 3 ` LAMAR. SLMTe '0 7 0 H O U STO N , *EXAS 7 7 0 1 0 -5 0 2 7 CHOMONS 7i3>7D-0*CS April 25, 1991 i-j0s~i:r2Tr p.oz ECO^'EP :fjlrf!'-r?CO Marvin Legator, Ph.D Dept, of Preventive Medicine & Community Health U.T.M.B. 24 KEILLER-F19 Galveston, Texas 77550 fax Re: Newman v. AT&T Dear Dr. Legator: I have an interesting case in which we have been asked to come in and take over for trial. Trail is set for June 24, 1991 in Denton county, Denton, Texas. Here is the case in a nutshell: AT&T bought a 2 acre tract of land from my clients. The tract of land is located at the top of a hill, in the middle of the property that my clients own. The rest of th property, aside from the tract of land sold, is used by the Newmans, (my client), for their residence and their farm. a t &t bought the property and situated a Microwave Relay Tower on it. At the time of the purchase, AT&T promised to maintain the vegetated growth on this easement by mowing the property. Contrary to their explicit promise, AT&T used and continued to use a herbicide. The continued use of the herbicide has caused many repercussions, not the least of which is that at least 65 trees have died or are dying on my clients property. AT&T admits spraying the property with the herbicide in 1972, 1973, 1974, 1975, 1980, and in 1982. AT&T hired Kem-Kil to do some of the treatments. A Kem-Kil employee testified that he thought they used a product containing Bromacll, also known as Hyvar-X, which is manufactured by DuPont. During this time period, AT&T also had their own employees apply some type of herbicide to control the growth on the easement. Unfortunately, A 0-V O' 2563 LhQf\tO. EXHIBIT _ _/ M. HKfDfefCKS {or perhaps conveniently?) AT&T can not locate its records which show the exact chemicals used. The family came down with symptoms that sees to correspond with the spraying. The mother was terribly fatigued to the point where,- for example, she was having difficulty working and began sleeping during her lunch hour. There are three daughters in `the family. They are Toni D/O/B 8/26/59. Trisha D/O/B/ 8/25/67. Xippie D/O/B 11/29/71. The daughter's symptoms appear worse then their mother's. Toni was advised by her doctors to have an abortion 24 weeks into her pregnancy. Trisha gave birth to a baby girl 34 weeks into her pregnancy on 2/15/88. The baby girl was born hydrocephalic. Xippie gave birth to a baby on 8/04/90. Trisha has been hospitalized several times since 1982, for numerous physical problems. She was hospitalized on 11/13/82 in an XCU suffering from extreme weakness, respiratory difficulty, very high levels of acetone, nausea, uncontrollable blood sugar from very high to hypoglycemic levels. During this stay at Flow Memorial, Trisha was extremely ill and in critical condition. Trisha was hospitalized on 4/26/83 for insulin allergy with irritation breaking out over her injection sites. She was hospitalized again on 5/27/83 for mononucleosis, fatigue, weakness, sinus infection, fluctuating levels of blood sugar and acetone. Trisha has suffered from extreme fatigue, weakness, respiratory problems, flu-type symptoms, numerous yeast infections, inability to keep insulin levels controlled, very high levels of acetone, muscle spasms, poor coordination, nervousness, edema, emesis, numerous sinus infections and poor kidney functions. Her problems were so extensive that she became homebound and tried to finish high school from home. [Note that prior to this she had not suffered from allergies and had not been sick much in her life.] Trisha delivered a baby on 2/15/88, 34 weeks into her pregnancy. The baby girl was born hydrocephalic. Surgery was done on the child on June 03, 1988. It has not yet been determined to what extent the child will be hampered in its development as a result of these problems. However, one apparent problem is that this child appears to be very sensitive, or what is often described as " allergic*' to everything. The other daughter, Toni was also pregnant. She 2564 h PR- 15 :Cl F^QM Lh U Fr !CE TO ,1'iQ' P . -\J, results to Dr. Robert J. Carpenter for a second evaluation. Dr. Carpenter recommended to Toni and her husband that it would be best to abort the baby. If not aborted the baby would be b o m severely deformed and would not have a chance of living. Issues concerning growth retardation were evident from the ultrasound. Toni had the abortion 24 weeks into the pregnancy on 5/05/88. The horses on the property had been mated several times and they were attempting to foal them with no luck following the herbicide use. Then on January 27, 1987, one of the mares had a colt. The colt died, and was diagnosed also as being hydrocephalic. There were also fourteen cats on the property before the spraying in 1982. After the spraying all the cats disappeared. Last summer, in 1990, my client took in a stray cat. The cat became pregnant and had a stillborn and deformed litter. As you can see, it is evident that we do have a very interesting case and we could use your professional expertise to help us. If you are interested in working on this case or have any further guestions, please contact me. If this is not an area which you are interested, I would appreciate your referring me to any other expert. Sincerely, 1- / ro* Annette Garza Legal Assistant cc: Tracey Conwell :gll 2AG/N03002.L4 2565 - l ? 9 i 15 :Q:Z FF.OH L h I-'I O F F I C E ^0 14097615172 p _ 7-20--SO - -65 2-23-72 - -72 3-25-74 2-20-75 3-31-75 4-26-75 3-17-77 - -77 4/7 7 3-16-77 CHRONOLOGY Newman/AT&T Maude R. Newman and husband, C.. Newman, sold to AT&T a 2.0 acre tract of land on a hill adjacent to their farm. Maude stored hay in the barn located between AT&T's property and Floyd & Jean Halberts property. Hay was ruined by a run off drainage from AT&T's prop erty. AT&T promised to build a ditch and not to spray any chemicals again. Marty Wright of AT&T was notified. AT&T contracted with Kem-Kil to spray 16,000 sq. feet for vegetation control. rNote: AT&T only owns approximately 9,600 sq. ft.] Maude noticed a purple substance had drained onto ner property from AT&T's property. AT&T contracted with Kem-Xil for vegetation control on 6,400 sq. rt. AT&T & Kem-Kil contracted to spray 6,400 sq. ft. for vegetation control. AT&T entered into a contract with Kem-Kil for vegetation control on 9,600 sq. ft. AT&T contracted with Kem-Kil for vegetation control Of 9,600 sq. rt. AT&T sprayed with their "in house" employees, cnemicals soraved are not Known. Several trees dying as well as the garden and peach tree owned by Floyd and Jean Halbert. Patns of dead grass leading from AT&T's property to the dead trees. Limbs of the dead trees sent to Texas A&M university Agricultural Dept, for Herbicide Test ing. A T & T & Kem-Kil enter into a contract for vegetation control. Denton is not included. Texas a &w concluded that tree had died of herbicide poisoning. 2566 p. a.tfc'l iiPF-X?-!??! rrCf'1 LhI.'J CFr!CE TO lSI1-!' P.0to 6-6-77 3-28-78 AT&T made a settlement with Floyd and Jean Halbert in the amount of $300. AT&T agreed it would not spray again. AT&T & Kem-Kil enter into a contract for vegetation control. Denton is not included. 6-5-78 AT&T made settlement with Maude Newman in the amount of $3,000. AT&T promised would not spray again. 3-30-79 AT&T contracted with Kem-Kil to spray 3,850 sq. ft. for the control of vegetation. 5-31-80 12-4-80 AT&T contracted with Kem-Kil to spray for the control of vegetation. Kippie was hospitalized at Flow Memorial Hospital, for extreme vomiting, fatigue, and abdominal pain. Upper GI series was performed. Results shoved abdominal pain probably due to gastroesphageal reflux; esphogitis probably due to above; and possible hypoglycemic state. 2-18-81 AT&T contracted with Kem-Kil to spray 9,600 sc. ft. for the control of vegetation. 82-12-84 Unable to allow animals to graze on pastures. 1-19-82 AT&T contracted with Kem-Kil to spray 9,600 sq. ft. for the control of vegetation. 3- -32 AT&T contracted with Kem-Kil to spray 9,600 sq. ft. for the control of vegetation. Spring 1982 Noticed dying trees. 9-22-82 Wesley Patton Halbert's dog taken for examination. Vet said dog suffering from `atoxia, astignas, nystagmus, and general lack of coordination; sug gested severe damage to central nervous system. 9-24-82 10-5-32 Dog was euthanized. TRAC report findings of 3romacil in Floyd & Jean's residence water, the stock pond and in the 320 ft. deep well. 11-13-82 Trisha hospitalized at Flow Memorial, ICU, for feeling bad; couldn't hold anything down; she had high levels of acetone, respiratory problems, -2- 2567 discharge diagnoses were: Diabetic ketoacidosis, Candida vaginitis, acuta sinusitis, hypoglycemia. 1- 33 Wesley Patton Halbert suffered poor muscle coordi nation, extreme fatigue, headaches, nausea, and mononucleosis. 2- 7-83 Dr. Gruaaro Garza performed several blood and urine tests on Wesley Patton Halbert. 3- -83 Trisha 10th grade; took Standford Test of Academic results showed she regressed back to the 8th grade level. 4- 26-83 Trisha admitted to Medical City Dallas Hospital suffering from recurrent problems with infections, cramps, ketonemia, ketonuria, and fatigue problems. 5- 27-33 Trisha hospitalized at Flow Memorial Hospital, suffering from acute severe mononucleosis, fatigue, weakness, severe tonsillitis, sinus infections, fluctuating levels of blood sugar and acetone. 1-9-34 Trisha and Kippie put on homebound school. 3-27-84 Results of Standford test showed Kippie scored lower than previous year. 3-28-84 Trisha diagnosed as chemically sensitive. 3/84-1/85 Floyd, Jean, Trisha, Kippie, Wesley Halbert put on massive doses of vitamins. 4- 2-84 Test performed on Trisha showed to have 11 differ ent toxicants in her blood and 6 different toxi cants present on the chlorinated pesticide screen ing test. 4- 9-84 Kippie diagnosed as having mononucleosis. 5- 7-34 Test performed on Kippie showed 12 different toxi cants in her blood and 5 different toxicants pres ent on the chlorinated pesticide screening test. 6-12-34 Kippie diagnosed as chemically sensitive. 3-1-84 Dr. Croissant removed warts on Wesley's penis shaft. 9-5-84 Wesley had to have his appendix removed. Dr. remarked appendix is unusually large. 2568 hP P -2 5 - 1 9 9 1 13 =3 4 FROM _HlJ O FFICE TO 1409~C152'~I' 10-3-84 Dr. Croissant removed 5 warts on Wesley's hands and penis. 4-1-85 Mare due to have colts in the simmer of 1985. They never had colts although they were rebred every year until January 1987. 4-12-85 Dr. Croissant removed 7 warts scattered over Wesley's fingers and pains of hands. Dr. stated to parents that "Wesley's immune' system had not fully developed, unable to fight wart virus." 5-14-85 Kippie Halbert attempts suicide. Diagnosed as suffering from atypical depression, PMS, allergies, food and chemical sensitivities. Severe depression due to hormone imbalance. 6-85 Liberty Christian conducted test on Trisha for next year. Results showed Trisha to be on 7th grade level. 1-27-87 Mare aborts colt. Vet diagnoses colt with hydro cephalus. Argyle Veterinarian clinic. 2-20-87 Trisha takes insulin this am without Benadryl but goes to work in barn for about an 1 to l 1/2 hours. Comes in and goes back to sleep. Mother wakes her up. Trisha can't speak, has slurred speech. Looks like she had a stroke. Appears to have been like a severe allergic reaction. 4-1-87 Kippie had her appendix removed. Dr. remarked "appendix unusually large." 12-30-87 Trisha has genetic screening. All genes normal. 2-1-38 Trisha has sonogram. 2-12-83 Trisha has sonogram, baby still appears hydroce phalic. 2-15-88 Trisha delivers baby by cesarean section, at 34 weeks into pregnancy. Baby born hydrocephalic. 4-3-88 Toni Ann Halbert Moon finds out she is pregnant. 5-6-88 5-5-33 Tony aborts baby 24 weeks into pregnancy because of abnormalities,' with clinical history of renal agenesis demonstrated by sonography. Trisha's baby, Megan, has surgery for hydrocepha lus. 2569 p-a.ti.1o 3/90 5/90 3-4-90 Megan's collar bone not connected. Maude R. Newman, chemically imbalance, started seeing Dr. William Cudd. K. Kippie delivers baby girl, Randi Ashlynn cissna. 2AG/N03002.C7 -5- 2570 TOTAL P .09 2571 /? , o M. Legator, P re s id e n t RECEIVED JUN 1 3 1991 M-C-T, INC. Toxicology Consultants Mutagens - Carcinogens - Teratogens General Toxicology I.D.#74 212 4899 70 Colony Park Circle Galveston. Texas 77551 Telecopier -(409) 744-6369 y i o S '.ooa-' MS. TRACEY CONWELL CADDELL & CONWELL ATTORNEYS AT LAW THE PARK IN HOUSTON CENTER 1331 LAMARR, SUITE 1070 HOUSTON ,'TEXAS 77010-3027 RE: NO. 82-4966-A; MAUDE NEWMAN ET AL V AT&T Dear Ms. Conwell: June 11, 1991 The following is an invoice for services rendered in the above referenced matter: RESEARCH AND CONSULTATION 1 1/2 DAYS (S3.000/DAY) $4,500.00 Yours truly 2572 2573 No. 82.-4966-A FILED 1991 JL 15 AM 9:^8 MAUDE R. NEWMAN, FLOYD W. HALBERT, JEAN A. HALBERT, TONI ANN HALBERT MOON, WESLEY PATTON HALBERT and FLOYD W. HALBERT and JEAN A. HALBERT as next friend of TRISHA KAY HALBERT and KIPPIE LYNN HALBERT, minors VS. AMERICAN TELEPHONE & TELEGRAPH COMPANY, ET AL. OF DENTON COUNTY, TEXAS 16TH JUDICIAL DISTRICT PLAINTIFFS' FIFTH AMENDED ORIGINAL PETITION TO THE HONORABLE JUDGE OF SAID COURT: COME NOW, MAUDE R. NEWMAN, FLOYD W. HALBERT, JEAN A. HALBERT, TONI ANN HALBERT MOON, WESLEY PATTON HALBERT, TRISHA KAY HALBERT, KIPPIE LYNN HALBERT, as next friend of KIPPIE LYNN HALBERT, and TRISHA KAY HALBERT as next friend of MEGAN MICHELLE RICHARDS, a minor (hereinafter referred to as Plaintiffs) complaining of AMERICAN TELEPHONE & TELEGRAPH COMPANY (hereinafter referred to as Defendant AT&T), KEM-KIL, INC. (hereinafter referred to as Defendant Kem-Kil), E. I. Du PONT De NEMOURS AND COMPANY (hereinafter referred to as Defendant Du Pont) and MIDLAND INDUSTRIAL WEED CONTROL, INC. formerly known as INDUSTRIAL WEED CONTROL, INC. (hereinafter referred to as Midland Industrial Weed Control) and would respectfully show unto the Court as follows: 2574 C.E. Newman, Defendant AT&T constructed or caused to be constructed upon said tract of land a microwave relay tower and building In connection therewith. V. CHEMICAL USE BY AT&T 5.1 Plaintiffs would further show that after the purchase of the AT&T Tract, Defendant AT&T contracted with various companies for the purpose of controlling the growth of any vegetation upon said tract of land by the application of herbicides and/or pesticides and/or various mixtures of chemicals. During certain years in the period 1960 until present date, Defendant AT&T also had their own employees, known as "In-house" spraying, apply herbicides and/or pesticides and/or various mixtures of chemicals for the purpose of controlling the growth of any vegetation upon said tract of land. Defendant AT&T has been unable to locate all of its records to provide Plaintiffs with the exact types of herbicides and/or pesticides and/or various mixtures of chemicals it has used in controlling the growth of vegetation since it purchased the property in 1960. VI. KEM-KIL TREATMENTS 6.1 Plaintiffs would show that Defendant AT&T contracted with Defendant Kem-Kil in 1972, 1973, 1974, 1975, 1980, and 1982 to furnish labor, equipment and material for chemical vegetation control on the AT&T Tract. -4- 2575 p-3.^ Defendant Kem-Kil admits it sprayed said property with a herbicide manufactured and sold by Defendant Du Pont under the brand name of Hyvar-X. VII. M.I.W.C. TREATMENT 7.1 Plaintiffs would show that Defendant AT&T contracted with Defendant Midland Industrial Weed Control, formerly known as Industrial Weed Control, Inc., in 1981 for the chemical treatment to prevent vegetation growth on the AT&T Tract. It is Plaintiffs' understanding that said property was sprayed with a herbicide and/or pesticide, but the exact mixture of chemicals used is not known to Plaintiffs at this time. VIII. AT&T IN-HOUSE TREATMENT 8.1 Plaintiffs would show that in 1976, 1977, and 1978 Defendant AT&T did not contract with a particular company to apply the chemical treatment to prevent vegetation growth on said tract of land, but instead ordered its own employees to spray with a herbicide and/or pesticide. It is Plaintiffs' understand ing that such herbicide and/or pesticide was purchased locally but the exact mixture of chemicals used and the amounts used is not known to Plaintiffs at this time due to the fact Defendant AT&T has been unable to locate its records and provide Plaintiffs with this information. -5- IX. AT&T CANNOT IDENTIFY CHEMICALS USED 9.1 Plaintiffs would further show that Defendant AT&T has also been unable to locate its records reflecting the exact herbicide, and/or pesticide and/or various mixtures of chemicals used for the purpose of controlling the growth of vegetation upon said tract of land during the years 1960 through 1971. X. 1965 PROBLEMS 10.1 In 1965 Plaintiff Maude R. Newman had stored hay in a bam located between the tract of land owned by Defendant AT&T and the house owned by Plaintiffs Floyd W. and Jean A. Halbert which is situated on the property owned by Plaintiff Maude R. Newman. Defendant AT&T had sprayed the AT&T Tract with a herbicide and/or pesticide and/or a mixture of chemicals unknown to Plaintiff. Following said spraying, it rained causing a water drainage problem off of the Defendant AT&T's property onto Plaintiffs' property. The run-off from said tract of land ran into the barn owned by Plaintiff Maude R. Newman and ruined the hay she had stored there. Plaintiff Maude R. Newman notified Defendant AT&T of said incident. At said time Defendant AT&T paid Plaintiff Maude R. Newman for the ruined hay and promised to dig a ditch to prevent water from draining down onto Plaintiffs' property in the future, which Defendant AT&T has failed to do. When Defendant AT&T inspected the ruined hay and promised to -6- 2 577 dig a ditch to prevent water from draining down onto Plaintiffs' property, Plaintiff Maude R. Newman reminded Defendant AT&T of their agreement to control the growth of vegetation on the AT&T Tract by mowing and that there was to be no use of chemicals of any type on said tract of land or along the road or the cattle guards, which Defendant AT&T acknowledged and promised to comply with. A short time after the RUN-OFF described herein, four large oak trees located in the vicinity of said barn died. XI. 1972 PROBLEMS AND PROMISES 11.1 In approximately 1972, Plaintiff Maude R. Newman noticed that a purple substance had drained onto her property from the AT&T Tract. Plaintiff Maude R. Newman notified Defendant AT&T by and through its maintenance supervisor, Marty Wright, who advised Plaintiff Maude R. Newman that Defendant AT&T had sprayed said area with a herbicide, pesticide and/or a mixture of chemicals to control the growth of the vegetation. Plaintiff Maude R. Newman advised Marty Wright that her young grandchildren frequently played in her yard and had been in the puddles of the purple substance and that she felt strongly that such use of any chemicals which affected her property was not safe for the health of her grandchildren or any farm animals and/or pets and would adversely affect any vegetation grown on her land. Again she requested that Defendant AT&T refrain from the use of any herbicide, pesticide and/or a mixture of -7- 2578 V chemicals to control the growth of vegetation and to abide by their previous agreement to mow said tract of land. Defendant AT&T's maintenance supervisor, Marty Wright, advised Plaintiff Maude R. Newman that Defendant AT&T would not spray or use a herbicide, pesticide and/or a mixture of chemicals to control the growth of vegetation again. XII. 1972 VEGETATION DIES AGAIN 12.1 In approximately 1977 Plaintiffs began noticing that several of their trees were dying as well as the garden and peach trees owned by Plaintiffs Floyd W. Halbert and Jean A. Halbert and that there would be paths of dead grass from the Defendant AT&T's property leading to the trees that had died. At that time Plaintiffs notified Defendant AT&T of the incidents mentioned above and inquired if Defendant AT&T had been using herbicides, pesticides and/or any mixture of chemicals for the control of the growth of vegetation on Plaintiffs' property. Plaintiff Jean A. Halbert and Defendant AT&T inspected Plaintiffs' property regarding the paths of dead grass, the garden, peach trees and other large trees that were dying. XIII. 13.1 To confirm Plaintiffs' belief that Defendant AT&T had again been spraying chemicals on the AT&T Tract, the roadway leading to the tower, and cattle guards, Plaintiff Floyd W. Halbert sent samples of the dead tree limbs to -8- 2579 Texas A&M University and U.S. Department of Agricultural Cooperating to be tested for herbicide poisoning. Said report dated May 16, 1977, reflected the diagnosis of "herbicide damage," a copy of said report is attached hereto and made a part hereof as Exhibit "A". 13.2 Plaintiff Jean A. Halbert advised Defendant AT&T of the results of said report. Defendant AT&T made a settlement with Plaintiffs Floyd W. Halbert and Jean Ann Halbert in the amount of $300.00 on or about June 6,1977, a copy of a document regarding said settlement is attached hereto and made a part hereof as Exhibit "B". Said Exhibit "B" states in part the following, to-wit: "...Payment of damages caused by spraying poison around tower yard and entrance to the Denton, TX. Site..." "...Runoff from poisoned area onto garden and peach trees caused loss of same and produce therefrom for the season;.." Since such time no fruit was produced and the three peach trees died. Further Plaintiffs Floyd W. Halbert and Jean Ann Halbert planted a garden in approxi mately 1981 and nothing would grow. 13.3 Defendant AT&T made a settlement with Plaintiff Maude R. Newman in the amount of $3,000.00 on or about June 5, 1978, a copy of said document regarding said settlement is attached hereto and made a part hereof as Exhibit "C". Said Exhibit "C" states in part the following, to-wit: "...Payment for damages caused by spraying poison around tower yard and entrance at the Denton, Texas Site..." -9- 2580 p.a. ...Runoff and overspray from poisoned area onto trees and shrubs caused loss of 2-20" oak trees, 1-12" oak trees, 1-hackberry, 1-bird of paradise tree, 1-15 year old yucca plant and minor damage to several other trees...* 13.4 Plaintiffs Maude R. Newman and Jean A. Halbert discussed with Defendant AT&T that the chemical spraying was dangerous and a hazard to the safety and welfare of humans and animals. Again Defendant AT&T agreed to control the growth of vegetation on the AT&T Tract and along the roadway and cattle guards by mowing and would not use herbicides, pesticides and/or any mixture of chemicals of any type. XIV. INDUCEMENT AND RELIANCE 14.1 Plaintiffs would show that they believed and relied on the represen tations, assurances and promises made by Defendant AT&T that the chemical spraying would cease and that it nor anyone employed by said Defendant would use herbicides, pesticides and/or any mixtures chemicals of any type to control the growth of vegetation the AT&T Tract or along the roadway or cattle guards. Such representations were material to, and induced Plaintiffs to accept the payment for, settlement of their claims for loss of the vegetation. Absent this agreement, Plaintiffs would not have agreed to the settlement. Plaintiffs relied on these representations further in that they believed they were not at risk. Had they known AT&T would ignore its promises and wilfully continue to use chemicals on -10- 2581 Q.Z-'o*0' the Denton tower site and surrounding area, then Plaintiffs would have taken further action to stop AT&T. More importantly, Plaintiffs would have had the opportunity to protect themselves from continued exposure to unwanted chemical exposure. XV. 1982 EVIDENCE OF POISONING AGAIN 15.1 Plaintiffs would further show that in the spring of 1982 they noticed several trees dying and paths of grass leading up to said trees were dead or grey colored. Plaintiffs immediately suspected herbicide poisoning. Upon inspection of their property, Plaintiffs counted approximately 65 trees that had been damaged to some extent or completely dead. In addition, Plaintiffs noticed that the fish they had stocked in their tank were dying. 15.2 In the summer of 1982, Plaintiffs noticed that Plaintiff Wesley Patton Halbert's dog was unable to walk without staggering and seemed extremely lethargic. Plaintiffs Floyd W. Halbert and Jean A. Halbert took the dog for examination on September 22, 1982, and were advised by David C. Coleman, DVM, that the dog was suffering from ataxia, astigmas, nystagmus, and a general lack of coordination suggesting severe damage to the central nervous system. It was his diagnosis that the dog suffered from toxic encephalitis consequential to the exposure to herbicides in the past and his recommendation that he should be euthanized, which was done on September 24, 1982. A copy of Dr. David C. -11- 2582 Coleman's report is attached hereto and made a part hereof for all purposes as Exhibit "D". XVI. 1982 WATER SAMPLES TESTED 16.1 In October, 1982, approximately six months from the most recent spraying of poison by Defendant Kem-Kil on the AT&T Tract, samples of water from their well which is 820 feet deep, stock pond and residence of Plaintiffs Floyd W. Halbert and Jean A. Halbert were tested by TRAC Laboratories, Inc. The analysis report stated that the results of the tests made on such samples showed the presence of Bromacil, a copy of said analysis report dated October 5, 1982, is attached hereto and made a part hereof as Exhibit ME". The report also showed high peaks of another substance that the lab suggested the Halberts test. However, the Halberts could not afford additional testing to identify the substance. Plaintiffs Floyd W. Halbert and Jean A. Halbert were advised that their well water was not safe to drink, thereby forcing them to purchase distilled water for drinking or install an activated carbon water filter. -12- XVII. DU PONTS PRODUCT 17.1 The herbicide Hyvar X which is manufactured by Defendant E. I. Du Pont de Nemours & Company consists of the active ingredient of 80% Bromacil (5-bromo-3-sec-butyl-6-methyluracil) and inert ingredients of 20%. Bromacil is a broad spectrum herbicide and was developed as a substitute for 2,4,5-T (2,4,5Trichloro-phenoxyacetic acid). Said 2,4,5-T was widely used in Texas to control the growth of vegetation on easements and right-of-ways in the 1940's 1950's, 1960's and 1970's, but was banned by the Environmental Protection Agency. Further, as per Defendant Du Pont's label instructions, Bromacil was to be mixed using the chemical 2,4-D. In studies investigating the residual nature of Bromacil after application, residues were still detected in the surface soil two years after application. Peaks in residues generally followed periods of increased rainfall by about two weeks. Defendant Kem-Kil sprayed chemicals on the AT&T Tract, roadway and cattle guards which is located on Plaintiffs' property at least once a year during the years 1972, 1973, 1974, 1975, 1980 and 1982. Plaintiffs believe that Kem-Kil mixed Bromacil, 2,4-D and diesel and applied that mixture of chemicals to the AT&T Tract, the roadway and cattle guards during the years set out above. -13- 2584 / .9v<V 8 * XVIII. ACTIVE INGREDIENT. INERTS AND CONTAMINANTS 18.1 From various studies, published articles and reports, the Plaintiffs have ascertained that an important principle for evaluation of the safety of commercial products is that one must be concerned with not only the major active component, but with the so-called "inerts," and with minor contaminants that may be present as a result of their formation during the manufacture or as the result of degradative reactions occurring in the environment. The Plaintiffs also believe that in mixing chemicals there is a danger of synergism, that is, that the toxicity is increased by combining the chemicals. XIX. TOXIC CHEMICALS 19.1 Herbicides as a family are neurotoxic, and chronic toxicity is difficult to detect and to evaluate. 19.2 Neurotoxic chemicals attack the central nervous system. Such chemicals may also attack the heart and liver and other organs. In addition, exposure to toxins on a chronic basis may alter the immune system resulting in immune system damage. The immune system, one damaged, may have increased or hypersensitive reactions to chemicals. In addition, the body's normal ability to fight infections and diseases may be diminished. Toxic chemicals are rapidly distributed to all tissues, especially the brain, liver, kidneys, -14- 2585 9-^ XXIII. WESLEY PATTON HALBERT 23.1 Plaintiffs would show the Court that in approximately January, 1983, Plaintiff Wesley Patton Halbert suffered poor muscle coordination, extreme fatigue, headaches, nausea, and mononucleosis symptoms. He continued to suffer these symptoms for several weeks. On February 7, 1983, Dr. Gumaro Garza performed several different blood and urine tests. As a result of such services, Plaintiff Wesley Patton Halbert incurred the following reasonable and necessary medical expenses, to-wit: Gumaro Garza, M.D. $ 182.50 TOTAL $ 182.50 23.2 Plaintiff Wesley Patton Halbert would further show the Court that in 1984 and 1985 he was treated for the removal of numerous warts on his body by Dr. R. S. Croissant. Dr. R. S. Croissant stated to Plaintiffs Jean A. Halbert and Wesley Patton Halbert that Plaintiff Wesley Patton Halbert's immune system had not fully developed and was therefore unable to fight the virus that was causing the warts to grow. Plaintiff Wesley Patton Halbert incurred the following reasonable and necessary expenses for such medical services, to-wit: 8/1/84 R. S. Croissant, M.D. 10/3/84 R. S. Croissant, M.D. 4/10/85 R. S. Croissant, M.D. $ 40.00 60.00 80.00 TOTAL $ 180.00 -32- 2 5 8 6 <).7.^n 23.3 Plaintiff Wesley Patton Halbert would further show the Court that he continued to suffer extreme fatigue, lethargy and irritable bowel syndrome. Plaintiff Wesley Patton Halbert incurred the following reasonable and necessary medical expenses as a result of the treatment and tests for his illnesses, to-wit: 7/18/85 7/18/85 7/22/85 7/23/85 7/24/85 7/27/85 7/29/85 7/30/85 7/31/85 8/1/85 8/2/85 8/6/85 8/7/85 WJR and Associates, Inc. Southwestern Clinical Laboratories WJR and Associates, Inc. WJR and Associates, Inc. WJR and Associates, Inc. WJR and Associates, Inc. WJR and Associates, Inc. WJR and Associates, Inc. WJR and Associates, Inc. WJR and Associates, Inc. WJR and Associates, Inc. WJR and Associates, Inc. WJR and Associates, Inc. $ 100.60 255.00 70.00 16.00 48.00 28.00 59.50 44.00 26.00 16.00 20.00 18.00 235.70 TOTAL $ 936.80 23.4 That as a result of Defendants' negligence, conscious indifference and intent in continuously exposing Plaintiff Wesley Patton Halbert to pesticides, herbicides and/or a mixture of chemicals, he has incurred medical bills which exceed $1,300, all of which were both reasonably required and necessitated by the exposure of pesticides, herbicides and/or a mixtures of chemicals to him. In all reasonable probability, Wesley Patton Halbert will continue to require medical care and attention and reasonable provisions should be made for such future medical attention and services. -33- 258 23.5 In September, 1984, Plaintiff Wesley Patton Halbert had to have his appendix removed. After the surgery, the surgeon commented to Plaintiffs Floyd W. Halbert and Jean A. Halbert that Wesley's appendix was unusually large, a copy of the hospital records is attached hereto marked Exhibit "P" and made a part hereof. 23.6 That as a result of Defendants' negligence, conscious indifference and intent in continuously exposing Plaintiff Wesley Patton Halbert to pesticides, herbicides and/or a mixture of chemicals, Wesley Patton Halbert has suffered great pain, discomfort, incapacities, disabilities, and mental anguish. He has been unable to lead a full and active life of a healthy teenager. In all reasonable probability he will continue to so suffer for the rest of his natural life, all to his damage. 23.7 That as a result of Defendants' negligence, conscious indifference and intent in continuously exposing Plaintiff Wesley Patton Halbert to pesticides, herbicides and/or a mixture of chemicals, Wesley Patton Halbert's parents, Plaintiffs Floyd W. Halbert and Jean A. Halbert, have suffered great emotional distress and mental anguish in worrying over the health, welfare and future of their son, Wesley Patton Halbert. There is no proper price for the anxiety and concern of a parent for the well-being of their child when that is threatened. Plaintiffs Floyd W. Halbert and Jean A. Halbert have expended much time, effort and money in attempts to care for their son, i.e., time missed from their jobs for -34- 2588 <D- Wesley Patton Halbert's numerous doctors' appointments and the expense for the trips for said appointments. 23.8 For each and ail of the damages, costs and expenses which Plaintiff Wesley Patton Halbert has sustained in the past, together with reasonable compensation for his pain, suffering, mental anguish, incapacity and future disabilities, Plaintiff Wesley Patton Halbert should be awarded fair, reasonable and adequate damages in the amount of $750,000.00. 23.9 For each and all of the damages, costs and expenses which Plaintiffs Floyd W. Halbert and Jean A. Halbert have sustained in the past, together with reasonable compensation for their pain, suffering, mental anguish, and emotional distress, Plaintiffs Floyd W. Halbert and Jean A. Halbert should be awarded fair, reasonable and adequate damages in the amount of $500,000.00. XXIV. TONI ANN HALBERT MOON 24.1 Plaintiff Toni Ann Halbert Moon would show the Court that she was pregnant with her first child in April 1988. Pursuant to her doctor's suggestion, labor was induced prematurely because of multiple deformities. The due date of her baby was supposed to be August 25, 1988. Plaintiff's baby girl was delivered prematurely on May 6, 1988, when a problem with the pregnancy was discovered by Plaintiff's doctor. The autopsy report stated that she had "multiple -35- 2589 congenital anomalies, with clinical history of renal agenesis demonstrated by sonography". 24.2 That as a result of Defendants' negligence, conscious indifference and intent in continuously exposing Plaintiff Toni Ann Halbert Moon to pesticides, herbicides and/or a mixture of chemicals, she has suffered, and will continue to suffer in all probability, great emotional distress and mental anguish. Plaintiff fears that any future pregnancy she has will be complicated because of her exposure to pesticides, herbicides and/or a mixture of chemicals and that any child born to her will suffer because of said exposure to pesticides, herbicides and/or a mixture of chemicals all due to Defendants' negligence, conscious indifference and reckless disregard. 24.3 For each and all of the damages, costs and expenses which Plaintiff Toni Ann Halbert Moon has sustained in the past, together with reasonable compensation for her past and future pain, suffering, mental anguish, incapacity and disabilities, Plaintiff Toni Ann Halbert Moon should be awarded fair, reasonable and adequate damages in the amount of $1,000,000.00. XXV. 25.1 Plaintiffs Floyd W. Halbert and Jean A. Halbert would further show the Court that as a result of Defendants' negligence, conscious indifference and reckless disregard in continuously exposing Plaintiffs to pesticides, herbicides and/or a mixture of chemicals that they have had to incur the expense in the sum -36- 2590 o- of $916.87 for the installation of one PSSAC-20 Activated Carbon Water Filter, which was both reasonably required and necessitated by the exposure of pesticides, herbicides and/or a mixture of chemicals to their property. Plaintiffs Floyd W. Halbert and wife, Jean A. Halbert should be awarded damages in the amount of $916.87. XXVI. 26.1 Plaintiffs Maude R. Newman, Floyd W. Halbert and Jean A. Halbert would further show the Court that as a result of Defendants' negligence, conscious indifference and reckless disregard in continuously exposing Plaintiffs and Plaintiffs' property to pesticides, herbicides and/or a mixture of chemicals, they have been damaged in their property. THey would be ethically and morally unable to sell the property to anyone-other than AT&T-after what has happened to them there. They have been further damaged in that they have been unable to grow fresh vegetables to eat. Not only have Plaintiffs been unsuccessful in their attempts to have a garden, they are afraid to eat products off their land and watered by their water. The Plaintiffs are unable to eat any fruit produced by their fruit trees because all fruit trees died after they were contaminated. They were unable to allow any animals to graze in their pasture from 1982 until December, 1984 for fear that said animals would become contaminated with said pesticides, herbicides and/or a mixture of chemicals. When Plaintiffs purchased three (3) miniature mares which grazed all over the Plaintiffs' property in 1985. Although -37- 2591 the mares were due to have colts in the summer of 1985, they did not. They never had colts even though they were rebred every year. Finally, in January 1987, one of the mares aborted her colt. Its head was visibly deformed and enlarged. Plaintiffs had a veterinarian at the Argyle Veterinarian Clinic check the colt and he diagnosed the colt. The colt had hydrocephalus. 26.2 Plaintiffs Floyd W. Halbert and Jean A. Halbert, in following the recommendations of various physicians and the experts who tested Plaintiffs soil and water, ate organic grown vegetables and used bottled water and/or chemical-free water carried from their neighbor's home to their home until their filter was installed. Said bottled water was used from approximately March 1984, until January 1985, with a minimum of five gallons per week. However, during this time Plaintiffs had to use the contaminated well water for bathing, cooking and cleaning. Said bottled water cost $6.00 per five gallon bottle. Plaintiffs Maude R. Newman, Floyd W. Halbert, Jean A. Halbert, Trisha Kay Halbert, Kippie Lynn Halbert and Wesley Patton Halbert incurred additional expenses as a result of having to buy said bottled water and were greatly inconvenienced as a result of having to use said bottled water and/or the chemical-free water hauled from their neighbor's home. 26.3 From March 1984 until March 1985, Plaintiffs Floyd W. Halbert, Jean A. Halbert, Trisha Kay Halbert, Kippie Lynn Halbert and Wesley Patton Halbert in following the recommendations of various physicians have been taking -38- 2592 9 .3l<p^ massive doses of vitamins in an effort to detoxify their systems of the chemical poisoning. Said vitamins cost approximately $50.00 per month. From March 1985 until present, Plaintiffs spend approximately $50.00 every three (3) months for vitamins. 26.4 Plaintiffs would further show the Court that they have suffered extreme emotional distress and mental anguish since learning that they had been continuously exposed to pesticides, herbicides and/or a mixture of chemicals due to Defendants' negligence. That all Plaintiffs have suffered from extreme fatigue, muscle spasms and nervousness. Also Plaintiffs Floyd W. Halbert and Wesley Patton Halbert suffered a loss of hair on their bodies. 26.5 Plaintiffs would further show that their property value has greatly diminished as a result of Defendants' negligence in continuously exposing said property to pesticides, herbicides and/or a mixture of chemicals. 26.7 For each and all of the damages, costs and expenses which Plaintiffs have sustained in the past, together with reasonable compensation for damages suffered in the future, Plaintiffs should be awarded fair, reasonable and adequate damages of at least $5,000,000.00, together with punitive damages in an amount of not less than $5,000,000.00. XXVII. 27.1 For the information of the Court, Plaintiffs would show that from Pesticide Chemicals Official Compendium. Association of American Pesticide -39- 2593 g-sytH Control Official, Inc., 1966, regarding Bromacii (ASA) under "Use Precautions" it states, "...Avoid contact with skin, eyes, and clothing. Keep away from children..." and under "Residue Tolerances" it states, "...None established..." and under "Application: Precautions", it states, "...Do NOT apply, or drain orfiush equipment on or near desirable trees or other plants, or on areas where their roots may extend, or in locations where the chemical may be washed or moved into contact with their roots. Do NOT use on lawns, walks, driveways, tennis courts, or similar areas. Prevent drift of dry powder or spray to desirable plants. Do NOT contaminate domestic waters..." A copy of said reference is attached hereto and made a part hereof as Exhibit "N". 27.2 Children tend to be more susceptible to pesticide, herbicide and/or chemical poisoning since their undeveloped immune systems are less capable of defending the body against toxic substances. XXVIII. 28.1 Defendants exhibited gross negligence and/or conscious disregard for the rights, welfare, property, health and safety of Plaintiffs in that: (a) AT&T consciously disregarded its promise to Plaintiffs not to use poisons on the AT&T Tract and easement. (b) AT&T did nothing to ensure that poisons were not used. (c) AT&T never supervised any work of the other Defendants. -40- 2594 i (d) Plaintiffs were never advised prior to or after Defendants sprayed the AT&T Tract. (e) Plaintiffs never received any precautions or advice from Defendants regarding the possible side effects and/or dangers from the use of said herbicides, pesticides and/or mixture of chemicals on the property hereinabove de scribed. (f) Defendants actively concealed their use of poisons; have denied and actively concealed their promises not to use more chemicals. (g) Defendants have concealed or refused to find documenta tion showing what chemicals were used. Exemplary or punitive damages should be assessed against AT&T. XXIX. 2S. 1 Plaintiff Maude R. Newman would show the Court that she and her husband, C. E. Newman, relied on and believed Defendant AT&T's assurances in 1960 when they sold Defendant AT&T the hereinabove described property that it would maintain the growth of vegetation on the hereinabove described property by mowing it and that Defendant AT&T would landscape same. -41- 2595 29.2 Plaintiffs would further show the Court that they relied on and believed Defendant AT&T's assurances in 19G5 when it acknowledged and again promised to comply with their original agreement that no pesticides, herbicides and/or a mixture of chemicals would be used to maintain the growth of vegetation on the hereinabove described property but that same would be maintained by mowing it. 29.3 Plaintiffs would show the Court that the Defendant AT&T took unfair advantage of Plaintiffs, all to Plaintiffs damage. Plaintiffs relied upon Defendant AT&T's acknowledgments and assurances that no pesticides, herbicides and/or a mixture of chemicals would be used to maintain the growth of vegetation on the hereinabove described property but that same would be maintained by mowing it. XXX. 30.1 Plaintiffs deny that their claims are time-barred. Further, should Defendants show that the claims may be barred by applicable statute of limitations, Plaintiffs assert that all of their claims were filed timely under the discover/ rule. That is to say, Plaintiffs filed their claims within the applicable time period following the date they knew or should have known they had a cause of action. -42- 2596 ) XXXI. 31.1 Plaintiffs incorporate the above-referenced facts and would further show this Court, as causes of action: 1. BREACH OF CONTRACT Defendant AT&T promised that it would control the vegetation on the tract by mowing and that it would not use pesticides, herbicides and/or a mixture of chemicals. Defendant AT&T breached that promise by applying, and hiring others to apply multiple chemicals for weed and vegetation control. As a result of this breach, Plaintiffs have suffered, and will continue to suffer, damages as more specifically alleged herein and hereby incorporated by reference. 2. PROMISSORY ESTOPPEL In the alternative, without waiving the foregoing, Defendant AT&T promised to Plaintiffs that it would control the vegetation on the tract by mowing and that it would not use pesticides, herbicides and/or a mixture of chemicals. It was foreseeable to Defendant AT&T that Plaintiffs would rely on these representations. Plaintiffs in fact relied and believed Defendant AT&T's assurances. Plaintiffs continued to live on the property without taking precautions that would have been taken if they had known the land and water were being contaminated. As a result of these assurances and of Plaintiffs' reasonable reliance thereon, Plaintiffs have suffered and will continue to suffer damages as more specifically alleged herein and hereby incorporated by reference. -43- 2597 ). a.k'T' 3. FRAUD Further, and without waiving the foregoing, Plaintiffs would show that Defendant AT&T made representations to Plaintiffs, as more specifically set forth hereinabove, with the intent to induce Plaintiffs to sell the tract to Defendant. Such statements were made knowingly or with reckless disregard that they were false. In addition, when AT&T paid Plaintiffs for the poisoned plants named in the attached agreements (Exhibits B and C), they promised not to use more chemicals. Yet they used more chemicals anyway. This amounts to fraud, or fraud in the inducement. Absent such promises, Plaintiffs would not have accepted the monies for the plants. Plaintiffs relied on such misrepresentations to the consequential injuries of Plaintiffs which injuries have been more specifically alleged herein and incorporated by reference. 4. NEGLIGENCE Ail Defendants owed Plaintiffs a duty of ordinary care. All Defendants breached that duty in applying poisons In a manner which exposed the Plaintiffs and their property.. Defendants Kem-Kil and Midland Industrial Weed Control should be charged with a higher duty of care. They should have been professionals with professional standards of handling and applying these toxic poisons. They were -44- net. Their actions fell far below the standard of care of an ordinary professional herbicide applicator. Defendant AT&T owed Plaintiffs a duty of ordinary care to select and supervise the applicators in applying poisons. Based on Defendant AT&T's representations and dealings with the Plaintiffs, Defendant AT&T should be held to a higher standard of care. Defendant knew or should have known that the Plaintiffs did not want toxic chemicals used at the AT&T Tract or easement because of the danger of exposure to Plaintiffs' property. Defendant AT&T knew or should have known that the chemicals often used for weed control may be extremely toxic. Yet AT&T did nothing. Their negligence exceeds ordinary negligence and rises to the level of gross negligence because AT&T's acts show a total lack of care or reckless disregard for the Plaintiffs' health, welfare and property. 5. NEGLIGENCE PER SE Further and without waiving the foregoing, Defendant Kem-Kil violated federal and state laws, including 7 U.S.C. I36j(a)(2), by the application of herbicides in a manner inconsistent with label directions. Further, Defendant AT&T is accountable for the actions of persons it authorized to apply the toxic chemicals to the property. The application of such materials is inherently dangerous or uitrahazardous and thus liability for the resulting harmful consequences cannot,be avoided merely because it was delegated to a third party. As a result of these violations. Plaintiffs have suffered, and wili continue to suffer damages as have been more specifically set forth herein and which are * hereby incorporated by reference. 6. INTENTIONAL AND/OR NEGLIGENT INFLICTION OF EMOTIONAL DISTRESS AND FEAR Further, and without waiving the foregoing, Defendants acted intentionally or recklessly in applying and permitting toxic chemicals to be applied so that the Plaintiffs and their property would be affected. Such conduct, as described more specifically hereinabove, especially in light of AT&T's promises to mow and landscape followed later by repeated promises not to use chemicals despite continuous knowledge of the trespass of the poisons to Plaintiffs' property, was extreme and outrageous, causing Plaintiffs to suffer severe emotional distress. Defendants acts were, at minimum, negligent in inflicting severe emotional distress. Any reasonable persons in Plaintiffs' shoes would have suffered extreme emotional distress. 7. TRESPASS Further, and without waiving the foregoing, Defendants negligently and/or intentionally permitted toxic substances to contaminate Plaintiffs' property notwithstanding the numerous complaints from Plaintiffs that Defendant AT&T -46- 2600 ? cease using toxic substances. As a result of this trespass onto Plaintiffs' property, Plaintiffs have suffered and will continue to suffer damages as more specifically alleged hereinabove and incorporated by reference. Defendants are jointly and severally liable for all of the damages which flow from the trespass regardless of whether such damages were foreseeable, 8. PRIVATE NUISANCE Further, and without waiving the foregoing, Defendant AT&T created a private nuisance by controlling vegetation on the tract adjoining to Plaintiffs' with ultrahazardous and/or toxic substances, and in such a manner as to contaminate Plaintiffs' tract with the run-off from such toxic substances. Such nuisance proximately caused Plaintiffs' damages as more specifically alleged hereinabove. 3. ULTRAHAZARDOUS AND INHERENTLY DANGEROUS ACTIVITY Further, and without waiving the foregoing, in applying the highly toxic chemicals whose use Is restricted by law, Defendants AT&T, Kem-Kil and Midland Industrial Weed Control were engaged in ultrahazardous activity in that the use of toxic herbicides necessarily involved a risk of serious harm to Plaintiffs. Defendants, in conducting the activity, knew or should have known that such activities inherently involved a risk of toxicity and trespass of toxic chemicals by air, land and water to adjoining property and residents. The injuries to Plaintiffs were a direct and proximate result of the activity for which Defendants are liable. -47- At all relevant times, Defendant AT&T, as the owner of the tract, knew or in the exercise of reasonable care should have known that the work to be performed for them by Defendant Kem-Kil and/or Midland Industrial Weed Control was likely to create a peculiar risk of bodily harm to others, including Plaintiffs, from exposure to highly toxic chemicals. AT&T is responsible for the acts of its agents. AT&T cannot delegate such ultrahazardous and inherently dangerous work to outside contractors and thereby avoid liability. In addition, Defendant AT&T failed to take any reasonable precautions against these risks. Such failure proximately caused the injuries to Plaintiffs described herein. Further, the damages suffered by Plaintiffs include, in addition to those described above: 1. The costs of moving, temporarily living somewhere else while thoroughly testing the land and water and, if necessary, remedi ating the site, and then moving back to their property; 2. The costs of future medical monitoring, cognitive and psychologi cal counseling; and 3. Anguish, fear, and emotional distress, including fear of cancer and other diseases, arising out of toxic exposure. -48- o-aio'b XXXII. PRAYER WHEREFORE, PREMISES CONSIDERED, each of these matters con sidered, Plaintiffs request that after trial and hearing of this matter that they be awarded fair, reasonable and just compensation, reimbursement and damages for the injuries and losses they sustained or could sustain as a result of the causes of action against Defendants as set forth herein. Plaintiffs further pray for prejudgment interest, post-judgment interest, costs of court, and for such other relief, general or special, legal or equitable, to which they may be justly entitled. Plaintiffs specifically pray that punitive damages be assessed against AT&T in an amount at least equal to actual damages. Respectfully submitted, OF COUNSEL Tom D. Jester, Jr. Minor & Jester 515 S. Carroll Blvd., Suite A Denton, TX 76202 (817) 367-7585 Trace. SBT o. 04718300 CADDELL & CONWELL 1331 Lamar, Suite 1070 Houston, Texas 77010-3027 (713) 751-0400 (713) 751-0906 FAX ATTORNEY FOR PLAINTIFFS 2603 9 . dSloO TOTmL P . 1 1 CERTIFICATE OF SERVICE I hereby certify that a true and correct copy of the foregoing instrument has been forwarded by certified mail, return receipt requested, this the 13th day of July 1991, to the following: Mr. David McCracken Locke Purnell Rain Harrell 2200 Ross Avenue, Suite 2200 Dallas, TX 75201-6776 ATTORNEY FOR KEM-K1L Mr. Neil Rambin Strasburger & Price 901 Main Street, Suite 4100 Dallas, TX 75202 ATTORNEY FOR AT&T John L Lancaster, III Jackson & Walker 901 Main, Suite 6000 Dallas, TX 75202 ATTORNEY FOR Du Pont J. T. Gandy, President Midland Industrial Weed Control, Inc. P. O. Box 3221 Midland, TX 79702-3221 PRO SE Mr. Ronnie Phillips 218 North Elm Denton, TX 76201 GUARDIAN AD UTEM N03002/POP.5thy -50- 2604 VT\ 20 ____ 2.0 2605________ -O srtofc #5 FIGURE 1: POSSIBLE MANIFESTATIONS OF MUTATIONAL EVENTS IN HUMANS Reduced Q uality of L ife 2606 0 3LlO*t M. HENDRICKS MEMO - 11/30/91 & LIST OF DOCUMENTS ON 2/4-D & 2/4/5-T Is" O CD CVJ MOYER FILE MEMORANDUM TO: RICHARD SCHULER FROM: JOHN BETTS SUBJECT: 2,4-D AND 2,4,5-T CHEMICAL FORMULAS AND KEY EPIDEMIOLOGICAL STUDIES DATE: NOVEMBER 30, 1991 The following material was collected from a variety of sources as follows: A. Chemistry formulation handbooks that explain exactly what is in these herbicides. (Mary Alexander's Personal Library). B. U. S. Food and Drug Administration Report (Davis v. Dow Files). C. Expert Witness File (Dr. Ozonoff) in Davis v. Dow files. D. Dr. Teitelbaum's personal file on key epidemiological studies. E. Dr. Frank Gardner's personal file on the most recent epidemiological studies to date. LISTING OF DOCUMENTS 1. 2/23/79: Blair, A., et al.,"Leukemia Among Nebraska Farmers: A Death Certificate Study", American Journal of Epidemiology. Vol. 110, No. 3. This showed a 183% increased risk for dying of leukemia in farmers born after 1900 and dying between 1957 and 1974 before the age of 66 years. Comment: It should be an even higher risk if the study were done now, considering it takes 10 to 25 years after exposure for many of these leukemia cancers to manifest. The herbicides were just starting to get used in the time periods of this study and there was an immediate change in these types of cancersl 2.. 11/5/82: Reed, Donald, "2,4-D Herbicide", Food and Drug Administration. Bureau of Foods. Internal Report on Herbicides in Foods. Comment: Shows that roughly 55-60% of 2,4-D is used on food or feed crops, while 40-45% is used on non-crop sites such as forestry, turf, and rangelands. 3.. Late 1980's: Sax, Irving N.,"Chemical Makeups of 2,4-D; 2,4,5-T; and TCDD" (selected pages on these chemicals), Dangerous Properties of Industrial Materials, Sixth Edition. 2608 O-a.7o? 4. Late 1980's: Verschueren, Karel,"Chemical Formulations and Toxic Properties of 2,4,5-T", Handbook of Environmental Data on Organic Chemicals. Second Edition. 5. 4/12/88: Zahm, S.H., et al., "A Case-Referent Study of SoftTissue Sarcoma and Hodgkin's Disease", Scand i. Work Environ Health. Vol 14, pp. 224-230. This found that the Soft-Tissue Sarcoma risk was higher among the farmers who themselves mixed or applied insecticides to animals in a Kansas study. This was associated with the chlorinated hydrocarbons in the insecticides. (Same as in the herbicides!). They talk about the reports from Sweden, Denmark, Italy and the United States that say persons exposed to the 2,4-D and 2,4,5-T herbicides have up to a 600% increased risk for soft-tissue sarcoma. 6. April 1989: Zahm, S.H., et al., "A Case-Control Study of SoftTissue Sarcoma", American Journal of Epidemiology. Vol. 130, No. 4, pp. 665-674. This looked at the same Kansas study and focused on non-agricultural workers, medical history, beverage consumption, and other factors on the incidence of soft-tissue sarcoma. Since the etiology of soft-tissue sarcoma is largely unknown, they wanted to see if any other factors were involved. The study found that users of the drug chloramphenicol produced a 540% elevated risk for this cancer. Other high risk groups were woodworkers and users of smokeless tobacco. Notes Maybe it is these same chemicals that are sprayed on the tobacco and on the trees in the forest or during processing at the mills. 7. Mar/Apr 1989: Alavanja, Michael C.R., et al,"Mortality Among Forest and Soil Conservationists", Archives of Environmental Health. Vol.44, No.2, pp.94-101. This report studies the USDA Forest Workers who died of cancer from 1970-1979. They found that non-Hodgkin's lymphoma (NHL) and colon cancer demonstrated a statistically significant linear trend with duration of employment as a forest or soil conservationist, which suggested an occupational etiology for both diseases. They found a 260% elevated NHL cancer risk and a 180% elevated colon cancer risk in the soli conservationists groups employed after 1960. Among the forest conservationists, the risk for both NHL and colon cancer appeared to be elevated before and after 1960. Comment: This study talks a lot about all the various kinds of cancers found at different levels of forest workers. 8. September 1990: Zahm, S.H., et al, "A Case Control Study of Non-Hodgkin's Lymphoma and the Herbicide 2,4-D in Eastern Nebraska", Epidemiology. Vol 1, No. 5, pp. 349-356. This study showed a 310% increased risk of getting non-Hodgkin's lymphoma for farmers who mixed or applied 2,4-D more that 20 days per year. The risk increased above this with the degree of exposure, as indicated by application method and time spent in contaminated clothing. 2609 0-M tO Comment; This clearly shows that the cancer risk is a function of time and duration of exposure, especially when wearing contaminated clothing all day! Q 1n / -l. \s / j1--Q*// Q_/_1!. nTUTu= Tu~.ar, f nJ\ f c : L . Q _L "Cancer Mortality amony Workers in Chemical Plant Contaminated With Dioxin", The Lancet. Vol. 338, No. 87731, pp. 959-964. This study supports the hypothesis that TCDD is a human carcinogen. It says that the relationship of malignancy in animals to TCDD exposure has been observed, but that of human carcinogenicity with TCDD remains controversial. The debate stems primarily from the inconsistent findings in case-referent studies relating risk of soft-tissue sarcoma and non-Hodgkin's lymphoma to herbicide exposure. Several investigators have detected a positive association but others have not. Epidemiological associations between TCDD exposure and other cancers have also been reported. They studied 1583 German workers in a herbicide plant that was contaminated with TCDD and found an increase for all types of cancers of 124%. Public concern over the potential hazards from disposal of waste products contaminated with TCDD and other higher chlorinated dioxins led to plant closure in June of 1984. 10. 10/26/91: Saracci, R. , et al., "Cancer Mortality in Workers Exposed to Chlorophenoxy Herbicides and Chlorophenols", The Lancet. Vol 338, No. 8774, pp. 1027-1032. They cite previous epidemiological studies that have revealed an increased risk of cancer, notably soft-tissue sarcomas and non-Hodgkin's lymphomas, in people occupationally exposed to chlorophenoxy herbicides, including those contaminated with TCDD. Here they did a historical cohort study of mortality in an international register of 18,910 production workers or sprayers from ten countries. The excess of soft-tissue sarcomas among sprayers is compatible with a causal role of chlorophenoxy herbicides. Four cases in four different countries all occurred after 10-19 years after the first exposure, a time shorter than that observed in Sweden or the USA. There was a 900% increase of Soft-tissue sarcoma noted among sprayers in particular, though not specifically for those probably contaminated with TCDD. 2610 Q -S .'lll