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. 7 with Dow Chemical September 1st, 1955, as an 8 entry-level industrial hygienist and radiation 9 safety specialist. 10 I began work In 1960 I transferred to the Texas 11 12 division as chief industrial hygienist, returned to Midland in 1962 as an industrial hygienist in 13 the same laboratory situation. 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. 20 In 1970 I became In 1971 I went back to health and environmental sciences as an industrial hygienist. 21 22 Williamsburg, Virginia, as director of industrial 23 hygiene, returned to Midland in 1978 as manager of 1976, I transferred to the Dow Badische Company in 2166 V'3 l3lG>3 8 1 industrial hygiene research and manager., of the 2 industrial hygiene lab. 3 4 MR. WAGNER: A 5 6 That's B-A-D-I-S-C-H-E. Then in December of 1979 it catches up to where I transferred to Dow Corning. 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 16 MR. WAGNER: A I object to the form. 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 23 MR. WAGNER: A Same objection. 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 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 10 11 hygiene manager, so during thattime period, if you know, with the company? A To the best of my memory, he was manager of 12 industrial hygiene for the Michigan division, was 13 the title. 14 Q 15 16 A Q It's the production division of DowChemical Do you know what other divisions are located in Midland, Michigan, other than the Michigan -- A 21 22 23 What located in Midland, Michigan. 19 20 before. was the Michigan division? 17 18 You mentioned thisMichigan division It's corporate headquarters for the company, so there are many corporate offices and functions going on there. Q Have you ever seen a flow chart or a diagram of 2168 10 1 the corporate organization in Michigan?, 2 3 MR. WAGNER: Q 4 At any point in time? During the time we're talking about, between '70 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 14 manufacturing process? 15 MR. WAGNER: 16 A 17 18 21 22 23 I object to the form. Wow, there may have been four or five, but not full time, to my recollection. Q 19 20 the Okay, when I spoke with — have you reviewed the deposition of Dr. Rowe? A No. Q Dr. Rowe mentioned that he thought, in the industrial hygiene division in the seventies, 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 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. 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 22 23 MR. WAGNER: Let me, as a point of I don't know if and apart from whether or not they were involved in the production end of it? MR. SCHULER: Correct. 2170 12 1 A 2 3 You fellows have thoroughly confused me. Would you restate the question, please? 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 7 8 That's a bit clearer, and I think my four or five is the best I can do. Q And as head of industrial hygiene during that time 9 period, Dr. Hoyle — 10 of the biomedical research lab? 11 A was industrial hygiene part Oh, another memory stretcher, it was part of the 12 biochemical research department when I joined in 13 the fifties. 14 mentioned the name was changed to health and 15 environmental research, I believe. 16 research is not biomedical, careful distinction. 17 Q 18 I understand. Somewhere in the time period you Biochemical Who did Dr. Hoyle report to between '70 and '75, if you know? 19 A Dr. Don D. Irish, for part of that 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. period, anyway. 2171 P'safes' 13 1 Q Not in Midland, Michigan? 2 A Delray Beach, Florida. 3 4 Actually it's too early for the eighth tee. 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 8 To the best of my recollection, Arnold Schaffer, S-C-H-A-F-F-E-R, Richard D. Olson — 9 10 M R . WAGNER: A O-N. O-N or E-N? The D is important because there's a Richard 11 A. there, too. 12 of our group at that time, and Edward J. 13 Schneider, S-C-H-N-E-I-D-E-R. 14 R-A-P-P. 15 Q George Florez, I believe was one Oh, Donald Rapp, 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? 6 changed, let me know that, too. 7 MR. WAGNER: 8 A And if they I object to the breadth. My recollection of that particular time period is 9 that my main effort was in two projects. 10 called Dow Environmental Health Services, a 11 12 One was consulting-for-fee effort to offer industrial hygiene and a number of other services to 13 industry. 14 that effort, which was headed up by Arnie 15 Schaffer. 16 I was the lead industrial hygienist for 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 22 23 Q Now, back in the 1960s, and I have some memoranda here that I'm going to show you in a minute, you 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 12 13 reasonable estimate, I want to hear it. A 14 15 a I was a good industrial hygienist, and I was available. 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 22 23 MR. WAGNER: I object to the form of the question, no predicate. 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 6 7 I don't remember specifics on that. I may have, but I just don't recall any specific project. Q 8 Had you investigated any cases of chloracne prior to 1964? 9 A I think one time, yeah. 10 Q And do you recall when that was? A Sometime, oh, a year Q About 1963 or so? 13 A Roughly, yeah. 14 Q Prior to that time had you investigated any cases 11 12 or so before, maybe. 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 23 MR. WAGNER: I object, asked and 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 5 yeah. 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. 14 compound that I cannot name for you at this point. It was a hexachlorophenolic 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 21 22 23 Well, I visited the plant to observe the actions of the employees, which is the standard initial step in industrial hygiene investigation. 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 14 specific -Q 15 16 A Well, that was phase one. Is there a question on the floor? Q 19 20 That's why I'm asking the question. 17 18 I'm not sure what you did. If that was phase one, what else did you do, what was phase two? 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 4 When you say in the plant, what are you referring 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 10 that applied to? A No. 11 MR. WAGNER: 12 THE DEPONENT: 13 MR. WAGNER: That — I'm sorry, I -That's all right. So we're 14 clear, you meant was there more than one building 15 producing trichlorophenol? i. 16 Q 17 Other than the building that he had responsibility for, right, producing trichlorophenol? 18 A Either way, the answer 19 Q That's what I understood your answer to be. 20 is no. was the building number, do you recall? 21 A It was 199 building. 22 Q And after becoming asafety 23 What officer and 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? MR. WAGNER: 14 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? MR. WAGNER: 19 20 A 21 22 23 I object to the form. At what time period now? During my health officer duties, yes. Q Okay. And was it part of your duties and 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: 7 I object to the form, 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? 12 go to the medical department first, to report this 13 before you became aware of it? 14 MR. WAGNER: 15 A 16 17 The answer How did that work? I object is yes, theywould Would they to theform. have gone to medical. Q And somebody, would somebody inthemedical 18 department then contact you to make you aware of 19 the problem? 20 A 21 theywould have — MR. WAGNER: 22 23 No, Iobject tothe form, calls for speculation and vague as to time. 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: 5 Same objection, calls for speculation. 6 A Yes. 7 Q And then he 8 would tellyou,and then you would 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 15 16 I don't know, for a particular year, how much we had. Q 17 Can you give me an estimate, to the best of your recollection? 18 A Before theevent, 19 Q Did you have occasion to see each one of the 20 about 60,as I recall it. 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 25 1 they transferred somewhere or what? 2 A They continued to work in the plant. 3 Q Do you recall the names of any of the workers? 4 A Wow. 5 Q Who was that? 6 Just one. MR. WAGNER: Let me stop you for a 7 moment, because I'm concerned about the medical 8 privilege, and in releasing confidential medical 9 information about that person, and I have not yet 10 gotten a direction from Dow as to whether or not 11 they want pursued by certiorari or not the court's 12 decision to require release of those names. 13 I don't -- Dick, why don't you go ahead. 14 At this point I'm going to instruct you not to 15 answer, but I'm going to ask you to let me know 16 the person's name before we get out of here today, 17 and I won't restrict Mr. Schuler from asking you 18 questions about that person, what he was doing, 19 what position he had, anything else he wants to 20 know, but for the moment let's not reveal his 21 name. 22 23 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. 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: 8 it some thought when we break. 9 Q 10 Dow He says he I understand, and I'll give Chemical wasinvolvedin making 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: 21 22 23 I object to the form, vague. A It's in the midst of a very large manufacturing 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: 5 question. 6 A Yes. 7 Q From 8 atimingstandpoint, that the January or February of 1964? A Yes. 11 MR. WAGNER: 12 of that as vague. 13 whom. 14 do yourecall chloracne in the 199 building was first noticed in 9 10 I object to the form of the Q 15 Let me object to the form It doesn't identify noticed by Was thechloracne mostly due to theexposure to 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 20 Now I need a repeat. (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? 4 A Waste stream. 5 Q Stream, okay. 6 I didn't hear you. Can you describe for me what the chloracne looked like that you saw? 7 MR. WAGNER: 8 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 14 organic compounds caused chloracne since 1941? 15 MR. WAGNER: 16 17 chlorinated I object to the form, imprecise as to Dow and attributing knowledge. A Some people in DowChemical knew that. 18 MR. LUTZ: 19 (The requested material was read by the 20 21 reporter.) Q 22 23 Would you read that back. Do you know which certain people at Dow knew that since that time period? 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 18 MR. WAGNER: Q I object, compound, vague. 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 23 MR. WAGNER: vague. I object, no predicate, 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: personal knowledge. 9 10 11 12 I object, vague, no A I believe so. Q And I think that, in your memoranda, when you 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. THE REPORTER: Wait a minute, is it TCBD 16 A Yes. 17 18 19 or TCDD? Q I'llask thequestion again to make it clear, your memoranda, TCDD was called TCBD? 20 21 A Yes. 22 Q And I'm going to refer to it as TCDDsince 23 in we have 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: 4 you're talking about the 2,3,7,8 isomer? 5 6 For clarification purposes, MR. SCHULER: Q Right. Was TCDD the primary culprit in the causation 7 the chloracne outbreak in 1964 at Dow Chemical 8 Company at the 199 building? 9 MR. WAGNER: 10 of I object to the form, calls 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: 22 23 I object to the form of the question. A Yes. 2190 O-AAi 7 32 1 Q Do you recall what those suggestions were? 2 MR. WAGNER: 3 4 evidence rule. A 5 6 The only one I remember specifically was a temperature limit for the process. Q 7 And what was the suggestion with regard to temperature? 8 9 Same objection, best MR. WAGNER: A Same objection. 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 4 5 I don't know it with certainty, but I believe it was around 200 degrees. 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 12 concerned? 13 14 A 15 16 MR. WAGNER: Temperature decisions? MR. SCHULER: Right. Engineers or plant management, I don't know for sure. Q 17 Do you know who the person who would have been 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 22 23 MR. WAGNER: I object to the form of the question. 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, 5 A I don't know, 6 honestwith THE DEPONENT: 7 8 to be toyour knowledge? you. I'd like to request a two-minute restroom break. 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. 11 did your responsibilities, if they did, end with 12 regard to chloracne and TCDD and the 13 trichlorophenol process? 14 MR. WAGNER: 15 16 A I need to hear that one again. (The requested material was read by the 18 reporter.) 19 THE DEPONENT: 20 Did you make your objection? 21 23 I object, breadth and vagueness. 17 22 At what point chronologically MR. WAGNER: A Then I can answer. time. Yes. There's no clearcut cutoff The way things worked, about 1967 I took on 2193 D-a.2.=)o 35 1 other responsibilities. 2 MR. SCHULER: 3 (Recess.) 4 BY MR. SCHULER: 5 Q Okay, let's take a break. 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: 9 10 11 12 I object to the form of the question. Q To your knowledge? A Yes. 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: 17 I object to the form of the 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: 4 5 I object to the form of the question, vague. A Only in general terms and with no certainty 6 because that's been a long time. 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 12 Q It would be So gloves were used and then washing. What type 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? 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: 23 vague, over broad. When I say barrier, I I object to the form, 2195 37 1 A 2 3 It was basically a closed process within vessels and piping and such. 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: 7 8 I object to the form of the question, compound, vague. A I'm not really sure what the question is, here. 9 It was basically closed. 10 product and waste streams, and there were joints 11 12 There were exits for within the piping, yeah. 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: 22 23 I object, over broad, time frame. 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 7 8 What type of respiratory protection, do you recall? 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 14 What type of company-supplied clothing did you 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 4 Did you put the safety recommendations into the 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: 13 I object to the form of the 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 21 22 23 A The purpose was to separate contaminated work clothes from street clothes. Q Were there any special instructions for washing 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, 6 special handling to avoid contact with the 7 contaminated clothing they were laundering. 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 13 in As I think you said you recommended two showers a 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 21 22 23 A No. A shower before the lunch break and then a shower at the end of the shift. Q Were there any special instructions for the showering, other than the normal shower with soap 2199 o azjo. 41 1 and water? 2 A Not that 3 Q Was the shower and wash time, I think you I recall. 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 13 for the particular plant, 199? A 14 15 It was a matter of months, six or seven months, I would guess. 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? 8 taken in some vat to another building where the 9 2,4,5-T or Silvex was made? In other words, was the trichlorophenol 10 MR. WAGNER: 11 12 I object to the form of the question. A 13 My recollection is it was transported in rail car 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: 21 22 23 I object to the form of the question. A I don't remember, to be honest with you. I've got 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 7 8 At the time I initially became involved, we didn't know what was in the caustic insoluble oil. 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: 13 waste oils, but the TCP, itself? 14 MR. SCHULER: This is not the caustic 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, 21 to the best of your recollection? 22 A Early 1965. 23 Q And who developed those 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 12 method that he developed the vapor 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 20 21 Yes. I'm trying to get a handle on that question. You're asking if I remember any amounts found? 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 6 that a little more fully for me? A 7 8 method at that time. Q 9 10 And what was the sensitivity, if you know, of the analytical method developed back at that time? A 11 12 Below the limit of detection of the analytical Early on, it was as high as ten parts per million of TCDD. Q 13 And then did that improve, later on, to some 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 23 A Okay. Over some period of time after the development of the method, it improved in stages 2204 0 - % 3o( 46 1 to one per million, one-tenth, 2 per million. 3 Q .01, I think, part 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 9 MR. WAGNER: A That's a mouthful. I object as to the breadth. You're asking if I know 10 whether any of the products were tested by the 11 analytical method? 12 Q Yes. 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: 16 breadth and vagueness. Same objection as to 17 A Generally non-detectable in products. 18 Q At what point in 19 A Mid sixties. 20 Q And what was the 21 time, if you recall? sensitivity level of the detection equipment? 22 A It improved over 23 Q Can you tell me what the level was, if you know, time. 2205 P-A302- 47 1 2 at a specific point in time? A 3 4 It was one part per million at some point in time, yeah. 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: 8 I object to the form, 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 22 23 reporter.) A I have no way of knowing. The answer is I don't 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: 6 I object to the form of the 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 23 A in the laboratory? Yes. 2207 P-J304 49 1 Q 2 3 What type of procedures did you institute at what point in time for that? 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 Nothing else specifically. 16 Q Were the lab people supposed to wear respirators, also, or wasn't that in the recommendation? 17 18 19 A I don't believe it was recommended. 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? 14 were any of those in the trichlorophenol? 15 Are you familiar with whether or not there 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 23 Q What about in the seventies? my knowledge. 2209 ■D-23ot, 51 1 A 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 14 MR. WAGNER: A Same objection. 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: 8 9 question. A 10 11 I object to the form of the The form of your question is -- I think the answer is I don't know. 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: 16 Contains undefined terms 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. 23 Dow Chemical Company for Silvex and 2,4,5-T in the Was that an established level by 2211 E?.a3otf 53 1 1960s? MR. WAGNER: 2 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 14 Q Was the agriculturalproducts division 15 so. located in Midland in 1974-75, the headquarters of it? 16 A I believe 17 Q And we're so. sitting here today in somebuildings 18 that have DowElanco on the front of it. 19 know the relationship between DowElanco and Dow 20 Chemical Company? Do you 21 A No is a good answer to 22 Q Do you know, at some point in time, was there a 23 that. 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: 5 He really doesn't know. Off the record. 6 (Discussion held off the record.) 7 MR. SCHULER: 8 9 Let's go back on the record. 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. 14 MR. WAGNER: 15 THE DEPONENT: 16 17 I wasn't involved. Your role is not to guess. Thank you, sir. I got tired of hearing myself say I don't know. 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, time frame. 12 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 20 21 The name is vaguely familiar, but I have no recollection of the gentleman or what he did. 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 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? 5 allyou know A I remember the name, 7 Q Do you know what 8 yes. his role was at Dow Chemical, to your knowledge? A 10 11 I'm probably mangling that name, also. 6 9 abouthim? My only recollection of him is as a chemist research scientist. Q 12 Did he have anything to do with 2,4,5-T, Silvex or 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: 17 I object as to the breadth, 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 23 any recollection? A I have no recollection. 2216 D. »313 58 1 Q Do you know a Dr. Hinman, 2 A Yeah. 3 Q Who is Dr. Hinman? 4 A For some period of time he was director of the 5 H-I-N-M-A-N? biochemical research lab. 6 Q Do you know approximately what point in time? 7 A No. 8 Q Sixties or seventies, 9 A Late sixties. 10 Q Do you know whether he did any research with 11 It would be guessing. can you be that specific? 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 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 Otis, yes. 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. 2 with this gentleman? 3 MR. WAGNER: 4 Do you recall meeting I object to the form of the 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: 16 I object to the form of the 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 22 A Yes. 23 Q Do you recall at the plant, itself? anyspecificrecommendations with 2218 O- 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 12 MR. WAGNER: A 13 14 I object, no predicate. V.K. Rowe, the director, Dr. Kenneth Olson, toxicologist. Q 15 What about the medical department, who did you 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 22 23 trichlorophenol, who did you deal with? A Ray Holmes, the superintendent, and A1 Lueck, the 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 17 Q Were there specific, to your knowledge, toxicology my knowledge. 18 files on the different chemicals, 2,4-D, Silvex, 19 2,4,5-T? 20 A Yes. 21 Q And where were those kept, if you know? 22 A In the 23 building where toxicology was located, 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: 11 I object to the form of the 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 20 may have taken your 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: 6 I object to the form of the question. 7 A 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. 17 time in the industrial hygiene group in Midland. 18 Timing is vague in my memory. 19 Q 20 21 He spent some When you say western division, what are you talking about? 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, 3 A Yes, with no H. 4 Q Was that division involved in manufacturing either 5 is that right? 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. 2223O ' 0 3 3 0 l 65 1 A I don't remember. 2 Q Do you know Marguerite 3 A Yes. 4 MR. WAGNER: 5 Q Marguerite. 6 A She was a scientist. Leng,L-E-N-G? Did you say Marguerite? Who isMarguerite Leng? My recollection of her was 7 as a member of the toxicology lab for some period 8 of time. 9 time in agricultural research department at Dow in 10 Midland. 11 Q 12 Vague recollection that she spent some Do you know what her role was with either the 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: 18 I object as to the breadth, 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 6 to do with that? A She may have, but I don't know for sure. 7 MR. SCHULER: 8 It's five to 12:00. 9 MR. WAGNER: 10 (Recess.) 11 MR. SCHULER: 12 You want to take a break? Q Sure. Back on the record. 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. 22 free to tell him. 23 If you reviewed things on your own, feel MR. SCHULER: If you reviewed documents 2225 67 1 of the company, I think it's included. 2 because you handed them to him -- 3 MR. WAGNER: Just His discussions or 4 preparations with me before this deposition, the 5 substance of that is work product. 6 MR. SCHULER: 7 discussions. 8 9 I'm asking if he reviewed documents. MR. WAGNER: Q It's work product. What have you reviewed, sir? 10 11 I'm not asking for MR. WAGNER: I'll instruct you not to MR. SCHULER: All right, we'll be back answer. 12 13 on that one, I'll guarantee you that. 14 Q Have you reviewed any depositions, sir? 15 A No. 16 Q Have youreviewed 17 documents? 18 A Yes. 19 Q What have 20 23 youreviewed that are Dow Chemical Company documents? 21 22 anyDowChemicalCompany MR. WAGNER: Q Same instruction. I want to be clear for the purpose of the record, so when we come back at your expense, that I'm not 2226 Q .0 3 * 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 6 MR. WAGNER: Q Same instruction. 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 22 23 you ever testified before the Environmental Protection Agency or any of its subcommittees? A No. 2227 D • 3-3SW 69 1 Q 2 Since leaving Dow in 1979, I believe you said, is 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 11 12 A No. Q Do you maintain contact, and when I say maintain 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. Q Who is Dr. Rampy? A He was, at the time, the director of industrial 21 22 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, 6 '92, somewhere in that range. '75 to '90 or '91, or 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 16 with? A Bruce Houhman, manager of industrial hygiene for 17 DowElanco. 18 here. Greg Socha is radiation safety officer 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? 2 A 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? 5 A 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? A No. 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 11 12 15 16 or -A 17 18 Last I knew she was part time with Dow Corning, industrial hygiene. 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 22 23 with that, did you ever communicate to any governmental agencies the fact that there was a substance in the trichlorophenol process that was 2230 72 1 2 causing chloracne in Dow workers? A No. 3 MR. WAGNER: 4 5 I object as to the predicate. Q 6 Did you ever communicate that fact to any 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 11 12 outside the company in any way? A Not that I remember. 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 17 A I don't know one way or the other. 18 Q Have you ever testified in any case or proceeding 19 or the other? involving any claim by any worker who got 20 21 22 A No. 23 Q I asked you earlier if chloracne as a result of working at Dow, whether it was 1964 or any other time? you testified in any civil 2231 73 1 cases where there were allegations of personal 2 injury from exposure to a Dow product. 3 testified in any cases whatsoever, civil cases, 4 where Dow Chemical Company was a defendant? Have you 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. 9 particular one happens to be Deposition Exhibit 10 10 to that deposition, and I'll ask you, first of 11 12 all, if you can identify that particular document? A 13 14 To the extent that it is, you know, entitled, and obviously I wrote it, yes, I can identify it. Q 15 16 This What is the document? Just give me a general identification for the purpose of the record. A It is a description of the part played by my 17 department, the biochemical research department, 18 in Dow's chloracne problem. 19 20 21 22 23 MR. SCHULER: And we'll just go ahead and mark that as Exhibit 1 to this deposition. MR. LUTZ: What exhibit was it to Rowe's deposition? MR. SCHULER: 10. 2232 D - P3SL? 74 1 (Plaintiff's Exhibit 1 was marked for 2 3 identification.) 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 — 11 that your handwriting? 12 A This, I don't think is. early Dow history of, is I'm pretty sure that 13 isn't, and I know that isn't. 14 look like my handwriting. 15 Q 16 That and the date Do you know whose handwriting this would be at the 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 22 trichlorophenol, and I've highlighted those words 23 there. identified and studied, are capable of producing Can you tell me what other compounds you 2233 D' 75 1 2 were referring to? 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 7 But they were not specifically identified at that point in time, is that what you're saying? 8 A At that point in time, this is March 11th, 9 Q I'm looking at page 2 of Plaintiff's Exhibit 1, '65. 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. 20 compounds are? 21 point in time? 22 23 A Again, do you know what those other Can you identify them at this They would be the families that I was then aware 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 7 8 in the trichlorophenol waste oil? A 9 10 But you're not referring there to other compounds I don't remember if that was meant to do that or not, to be honest with you. Q You refer in the last sentence to some European 11 experience with chloracne. 12 you're referring to there? 13 A Can you tell me who 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. 18 all I remember of it. That's about 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. 4 see that there? Do you 5 A Yes, this part that 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 12 you'vehighlighted? befromtoxicology, our toxicology department. 13 MR. WAGNER: For purposes of the record, 14 if this is ever offered at trial, this document, 15 want to object to the highlighting of it and would 16 want a clean copy submitted, as opposed -- 17 MR. SCHULER: 18 19 I You'll certainly get a clean copy. 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. 23 there? Can you tell me what you are referring to 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. 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 17 It says the something The handwritten insertion appears to be the word phenate. 18 Q Is that your writing or was that someone else's? 19 A I can't tell. 20 Q Can you make out the handwritten scratches that It's too indistinct. 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. 5 Q You mention at the top of page 4 in Plaintiff's I don't recognize that writing. 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. 11 companies you referred to earlier, Boehringer, and 12 you couldn't remember the names of the other two? Are those the same 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 23 there? A Yes. 2238 £>. 9335" I 80 1 Q 2 And when you say active, are you referring to causing chloracne? 3 A No. 4 Q What 5 A To cause folliculitis in theanimal, are you referring to? or the rabbit 6 ear, and there's a technical difference between 7 that and chloracne. 8 Q 9 10 betweenfolliculitis and chloracne? A 11 12 Whatis the difference I'm not a medical person, so I really just as soon not give you an answer, if that's all right. 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 16 17 I think that's a good answer, I don't feel qualified. 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: 4 Are you asking what that 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 10 you the chemical components, okay? 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 2 chloracne there or some other problem? A 3 4 I'm referring to causing folliculitis in the animal tests, specifically. 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. 9 what you mean by that? 10 MR. WAGNER: 11 A Let me show you that and ask you I object to the form. 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 15 You're referring to the strength of the contaminant there? 16 MR. WAGNER: 17 I object to the form of the 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 6 A Toxicology. 7 Q Do you know who was conducting these tests at this 8 9 from? time in 1964? A 10 11 get thatinformation To the best of my knowledge, it was Dr. Kenneth Olson. Q 12 He was a toxicologist with thecompany at that of thefirst full time? 13 A Yes. 14 Q You mention at thebottom 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. 20 see that last sentence? 21 A Yes, I see it. 22 Q Was that information 23 yougot Do you fromtoxicology, 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 5 MR. WAGNER: Q I object, the predicate. 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: 11 I object to the form of the question. 12 A I honestly don't remember. 13 Q There is a reference in the last paragraph to a 14 Mr. Skelly. 15 the analytical lab? Was he one of the toxicologists in 16 A No. 17 Q What was Mr. Skelly? 18 A Analytical chemist. 19 Q And what division or 20 A Analytical laboratories. 21 Q Is that part 22 A No. 23 Q Separate? department was he in? of the biochemical research lab? 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. 5 identify that by-product? Was he the first one in the company to 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 14 Do you know if that was yours or someone else's? A 15 16 That doesn't look like my handwriting. I don't know whose it is. Q In the next sentence you refer to two materials 17 that were identical from infrared melting point 18 analysis. 19 there? Do you know what you're referring to 20 A I don't know what that refers to. 21 Q Was Harold Gill in the analytical laboratory also? 22 A Yes. 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 — 6 TCDD, down to one part per million by weight, do 7 you see that there? I guess of the 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 16 toxicology also? A 17 18 The part relating to the rabbits from toxicology, and the other from analytical. 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: 3 MR. WAGNER: 4 A Okay to answer? Sure. Because the analytical samples, process samples 5 had lots of interferences. 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 Starting with pure So you took the pure and diluted the pure to five 10 parts per billion? 11 if you will? You worked up instead of down, 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. 19 whether you did that or that was somebody else? 20 A 21 Again, do you know Just about impossible to tell, but I don't think I 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: 9 MR. WAGNER: 10 A Okay? Okay. My wipe test samples were tested on the rabbit ear 11 because of its great sensitivity. 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 At the same 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 3*// D-a 89 1 A That's 2 Q And the chemical analysis was done with the vapor 3 correct. 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 9 Q There's a sentence scratched out at the end that best of my recollection. 10 talks about the chlorinated dibenzofurans were 11 tested on animals many years ago and shown to be 12 quite active. 13 information came from? 14 MR. WAGNER: 15 Do you recall where that I object to the form of the 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. 22 you recall what products you were referring to 23 there? Do 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 7 record for me? A Peaks coincided with some unknowns which were seen 8 in wipe samples and process samples. 9 biochem lab and the Germans have reported animal 10 tests with these compounds which showed acnegenic 11 activity. Both the 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, 4 think the word is made, M-A-D-E, from 5 trichlorophenol. 6 developing a quality control specification for 7 TCBD in consumer products. This project is aimed at 8 Q Do you know who was 9 A No. 10 Q Do you know what standard 11 12 incharge of that project? was ultimately developed? A 13 14 I During the time I was involved, our standard was nothing detectable in the material. 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? 2 know that was before you were with the company, 3 but you referred to precautions. I 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. 12 located and whether or not Dow Chemical had an 13 interest in it? Do you know where that company was 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. 19 you author that letter? 20 A No. 21 Q Do 22 A No. 23 Q It mentions you Did know who did? that the letter answered seven 2251 P-234# 93 1 specific questions regarding our own plant 2 experience. 3 were? Do you recall what those questions 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. 9 in doing that survey? 10 A 11 12 Do you know who was involved That was my assignment to the plant being referred to there. Q 13 And that was, I forget the fellow's name, who was 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. 7 how many? Do you recall 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 15 A I would guess so, yeah. Chemical? 16 MR. WAGNER: 17 THE DEPONENT: 18 MR. LUTZ: 19 You are right. Does that mean you are changing your last answer to you don't recall? 20 THE DEPONENT: 21 I'll change my last answer to I don't recall. 22 23 Don't guess. MR. LUTZ: Q I had to say something. You mention at the top of page 10 of Plaintiff's , 2253 • 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. 4 of those objections in written form, if you 5 recall? Were any 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 12 Plaintiff's Exhibit 1 that a health supervisor is now stationed at the 349 building. 13 Do you recall 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. 17 components were of that particular chemical? Do you know what the 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. 4 know what activity was shown on the rabbit ear 5 that you're referring to there? Do you 6 A Where the heck are we here? 7 Q Here. 8 A That's not 9 Q Right here, I'm sorry. A That's the folliculitis activity. Q You distributed this March 10th, 1965, memorandum 10 11 12 what — 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: 16 17 I object to the form of the question. 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 21 A Filing purposes, strictly. 22 Q Was there computerization of these things back in 23 purposes? 1965, or was it manual? 2258 10 0 1 MR. WAGNER: 2 I object to the form of the 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: 7 I object to the form of the 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? A Under distribution is Hutchenreuther. Q And where was he located at the time? A He was a manager in the Midland plant at the time. 11 12 13 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. 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 22 23 It mentions a J. Kelly. disposal. A I can't read -- oh, Amstutz, It says something Who is that individual? 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 6 the time. Q 7 And I think Bailey we have covered. And the last name -- 8 A Sculati. 9 Q What was his position? 10 A He was plant superintendent, but I don't remember 11 12 Q At one of the buildings? 13 A Yeah. 14 Q Let me show you this document and ask you if you where. 15 can identify that? 16 A Yes. 17 Q What is it, first of 18 A It is the, a report of a meeting held at the 19 all? biochemical research laboratory. 20 Q What is the date? 21 A Memo is dated March29th, 1965. 22 23 MR. SCHULER: We'll mark that as Exhibit 2. 2280 V- 102 1 (Plaintiff's Exhibit 2 was marked for 2 3 identification.) Q 4 5 Mr. Silverstein? A Q 8 9 If you referring to the document we just looked at, yes. 6 7 Plaintiff's Exhibit 2 is a report authored by you, And what was the purpose of this report, Plaintiff's Exhibit 2? A 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. 20 That appears to be V.K.R., 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- 10 3 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. 7 ask you, do you know what he was referring to in 8 the context of that meeting? 9 MR. WAGNER: 10 11 12 Again, I'll I object to the form of the question. A The number of other compounds in the caustic 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, 17 was it someplace else? 1701 building, or 18 A I don't remember which 19 Q But it was on the Dowpremises? 20 A Yes. Q On page 2 of Plaintiff's Exhibit 2, you mention 21 22 23 building it was in. that Dr. Holder reviewed the medical side of the 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. 11 12 there, just the cases from the 199 building? A I couldn't 13 A I couldn't tell you what Dr. Holder was referring to at the time. Q You mention that he showed slides of the more 18 dramatic cases. 19 the slides yourself? 20 A Yes. 21 Q Did he 22 23 I object to the form of the question. 16 17 tell you. MR. WAGNER: 14 15 Are you referring to, Did you have a chance to observe put them in a slide projector and put them up on a screen, is that the way he did that? A Yes. 2263 O . a 2>to 105 1 Q 2 Do you remember how many slides there are that he showed? 3 A No. 4 Q You mention thathe reviewed clinical studies that 5 were being made on these people with emphasis on 6 the liver function tests. 7 said about the impact of these unknown acnegens 8 and the TCDD on liver functions? Do you recall what he 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. 13 about that? Do you recall what he said 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 3 A Yes. 4 Q You also made a presentation 5 Company? at thatmeeting, is 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. 11 recollection? Does that refresh your 12 A Yes. 13 Q And you can look at this to further refresh your 14 recollection, if you would like. 15 bottom of page 2 of Plaintiff's Exhibit 2. 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 22 23 MR. WAGNER: It's at the very Was it I object to the form of the question. A I need a rerun of the question because it got a 2265 £• 3 3 k a. 1 07 1 2 little long. 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: 9 I object to the form of the 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 16 Q With water alone? 17 A Mm-hmm -- yes. 18 Q Yes. 19 A Water, detergents and vigorous it could be done. I'm sorry, you said water alone? « 20 21 scrubbing was required. 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: 5 I object to the form of the 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. 13 recollection of the limit of detection of the 14 machinery at that time? 15 A 16 Is that your At the time -MR. WAGNER: I object to the form of the 17 question, since the paragraph refers to two limits 18 of detection. 19 A 20 21 My recollection at the time, for the sentence highlighted, yeah. 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-3 l3(o ^ 109 1 not afford to sell contaminated products. 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: 7 question/ over broad and vague. Was I object to the form of the 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: 16 17 question. A 18 19 I object to the form of the I have no recollection of any comments by anyone at the meeting at this time. 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: 7 I object to the form of the 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 16 information? 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. 6 air samples that you collected? Were those 7 A Yes. 8 Q And were they collected from the 199 building, is 9 10 that what you're referring to? A 11 12 I'm not sure, at this point, where they were collected. Q There is a postscript on Plaintiff's Exhibit 2, 13 that's page 6. 14 Rowe, or is that something that you wrote? 15 A Is that a postscript from Dr. 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: 21 your thoughts, let's take a break. 22 23 While you are collecting (Recess.) BY MR. SCHULER: 2270 V-S'Sil 11 2 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 — 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 will let him 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. 20 on i t . 21 MR. WAGNER: The judge ruled 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 1 13 1 waived it for everybody else; I can't object. 2 can't go to the 5th D.C.A. 3 a waiver in any other context. 4 MR. SCHULER: I don't want it to be In other words, the fact 5 that he discloses the name will not prevent you 6 from taking the appeal? 7 MR. WAGNER: 8 MR. SCHULER: 9 MR. WAGNER: 10 MR. LUTZ: I Correct. I'll agree to that. Go ahead. 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 23 still with the company or still in Midland or not? A No, I do not. 2273 a a 7o 11 5 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 16 identification.) 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. 23 other than a lawyer, feel free to give him that. If you've heard about it from a source 2274 O-33'll 1 16 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, 12 A Correct. 13 Q And it's 1964, correct? broken down into various sections. 14 says dictated February 24th, 1976, as you 15 testified earlier. 16 February 24th, 1976, do you recall? 17 19 Why was this dictated on MR. WAGNER: 18 I object to the form of the question. A 20 Yes, I do recall. It's because I was about to transfer to Dow Badische -- 21 Q Which we 22 A -- in Williamsburg, and wanted that 23 It spelled earlier, I think. donebefore I lef t . 2275 p- 237P- 11 7 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. 15 ever questioned about this particular document in 16 other cases? Were you 17 A I don't rememberspecifically. 18 Q There appear to be some edit marks at various 19 points in this document. 20 edited the document or whether it was edited by 21 someone else? Do you know whether you 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? 3 A 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. 12 the name of the assistant plant superintendent 13 that you were referring to there? My question to you is, do you recall 14 A Yes. 15 Q Who was that, sir? 16 MR. WAGNER: 17 Same understanding with referring to identifying the person's name? 18 MR. SCHULER: Yes. 19 A I can answer? 20 Q And that is the Mr. Lueck who I think appeared on 21 the routing slips for some of the other memoranda? 22 23 Al Lueck, L-U-E-C-K. MR. WAGNER: question. Object to the form of the 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 12 Q Do you remember the names I said of any noearlier. of the 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 23 A The latter,yeah. latter? p. 23*7^ 1 20 1 Q You mention on page 7 that you, Larry Silverstein, 2 were the first full-time safety officer. 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 Are you 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. 12 you recall the frequency of those safety training 13 indoctrinations? Do 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: 20 I object to the form of the question. 21 A Repeat the question. 22 Q Were there any assistants that 23 would have conducted these safety training indoctrinations 2279 D-937C. 12 1 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. 9 help refresh your recollection at all about who 10 the companies may have been? 11 A 12 Does that Well, I think I've mentioned Boehringer in 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. 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 With 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. 14 that comport with your recollection today? 15 MR. WAGNER: 16 Does Object to the form of the 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. 23 standard that existed, to your recollection, when Is that the limit or the 2281 123 1 you did this memorandum in February of 1976? 2 MR. WAGNER: 3 I object to the form, 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: 16 I object to the form of the question. 17 A I honestly couldn't answer that. 18 Q When you refer to plant 19 supervision, what are you 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'? 12 4 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. 12 referring there to the end product, to the esters 13 2,4,5-T? Are you 14 A Let me see 15 Q Sure. 16 A It would refer to the esters specifically, as I 17 the statement. read it. 18 Q The esters 19 A If you're — 20 of 2,4,5-T? if you're using 2,4,5-T to denote the 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: 4 Object to the form of the 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 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 mean A-M-I-N-E — 15 safety precautions brochure of five or six pages 16 regarding the handling or laboratory handling of 17 the TCDD. 18 within the company? 19 Do you know where that would be located MR. WAGNER: 20 It's the one he provided to the government? 21 MR. SCHULER: Yes. 22 Q Do you know where that would be in the company? 23 A No, I don't. 2284V ■ 2 3 '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. 4 you know where that would be kept? 5 MR. WAGNER: Do 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 15 I don't know at what prison, but it says the 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. 23 prepared, or was that prepared somewhere else? Is that something you 2285 V- 127 1 A I prepared this originally, yes. 2 Q And where did you get the information to prepare 3 4 this from? A 5 6 The human data came from Kligman's report. The animal data came from Dow toxicology. 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: 10 11 question; undefined terms, vague and over broad. A 12 13 Object to the form of the At the time it was considered, I believe, to be valid information. Q And would you have gotten the information 14 regarding the Kligman prisoner experiments from 15 the toxicology department? 16 A Yes. 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 23 studies? 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 6 7 Do you recall the name of the individual or individuals who conducted the follow-up studies? A 8 Dr. Ralph Cook, M.D., was the head of 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: 16 Object to the form of the question. 17 A I don't understand your question. 18 Q How long were the workers followed after 1964? 19 A I really don't know the answer. Do I — There's a 20 publication on it, but I don't remember when it 21 came out. 22 23 Q Do you remember what decade it came out, the sixties, seventies, eighties? 2287 D -S3SY 12 9 1 A 2 I think it was the seventies, but even that is 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 10 11 12 13 scientific journal or not? A Yes. Q Do you recall what journal it was published in? A I believe it was the Journal of Occupational 14 15 Do you recall whether the study was published in a Medicine. Q 16 And indirectly I asked you this before, but do you recall what year it may have been published? 17 A I don't remember the 18 Q As far as your responsibiliy is concerned, I take year. 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 industrial hygienist? 2288 0-331^ 13 0 1 A No. 2 MR. WAGNER: Object to the form. 3 Q Did you? 4 A Yes. 5 Q What did you 6 A I estimated the categories of exposure for the 7 8 do? workers being studied. Q Were yourresults committed to writing? 9 MR. WAGNER: 10 In a form other than the article that was published? 11 12 A I don't recall. 13 Q Do you remember what the results were of your MR. SCHULER: 14 Yes. 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, 20 Q Did you do anything else other than estimate 21 22 23 yeah. exposures in connection with the follow-up study of the 1964 workers? A Not to my recollection. 2289 P- 131 1 Q 2 To your knowledge, and this was an in-house Dow study, correct? 3 MR. WAGNER: Object to the form of the 4 question. 5 you mean all the authors were Dow employees? Let me ask a clarifying question. 6 MR. SCHULER: Correct. 7 MR. WAGNER: Okay. 8 A Yes. 9 Q And there wasn't anybody brought 10 Do in from the outside, any independent laboratory or scholars or 11 12 anybody to take part in the study? MR. WAGNER: 13 Object to the form of the 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 23 any other epidemiological studies done within the Dow Chemical Company with 2290 13 2 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 whether anyone 7 was included inthat study that did not evidence chloracne? MR. WAGNER: 8 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 originally. 16 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. 22 tell. 23 Is that March 14th? I can't (Plaintiff's Exhibit 4 was marked for 2291 !0' 1 33 1 2 identification.) 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: 10 11 12 Object to the form of the question. A I'd like to see it, here. 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: 17 question. 18 Q In your opinion? 19 A That's correct. 20 Q And product was 21 22 23 Object to the form of the sold to Riverdale and Woodbury at some point, correct? A My recollection -- MR. WAGNER: Object to the form of the 2292 D -P -3 V J 13 4 1 2 question. A — was that it was proposed to be transferred to 3 some other place, and those two names sound 4 familiar. 5 Q I do not recall that it happened. Well, look at the memorandum and see if the 6 memorandum refreshes your recollection. 7 predicate question, Woodbury and Riverdale are 8 what type of companies? As a 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: 13 14 Object to the form of the question. 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. 21 remember it being shipped. 22 don't know what happened to it. 23 Q It doesn't say we shipped it. I don't I don't know. I just 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: 4 Object to the form, over 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 20 Do you know who would have been responsible for the reprocessing? 21 A No. 22 Q Do you recall any complaints from Dow customers 23 from, say, 1964 through 1976, regarding any 2294 13 6 1 chloracne from any of the 2,4-D or 2,4,5-T or 2 Silvex products sold by Dow? 3 MR. WAGNER: 4 Object to the form of the question. 5 A No. 6 Q If there were some complaints, would 7 you be 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 — 16 2,4-D, 2,4,5-T or Silvex? 17 the causing of cancer in any- users of MR. WAGNER: 18 Object to the form of the question, vague,over broad 19 A No. 20 Q And I assume your answer would as to time, be thesame as well. 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 2 Are you being paid for your time in testifying in 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 Environmental Engineers, 11 A That's correct. 12 Q And what is your understanding of the compensation Inc.? 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 18 A Yes. 19 Q And is it your understanding that Dow Chemical A 22 23 time? Company is paying that amount to Farlow? 20 21 preparation and deposition My understanding that Dow Elanco will pay Farlow, yes. 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: 3 Object to the form of the 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, 8 Q Do you get any type of credit for that billing? 9 A No. 10 Q In other words, you yes. hire your time out, your 11 employer charges for your time, and you get paid a 12 straight salary? 13 MR. WAGNER: 14 Object to the form of the 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: 19 A I didn't understand. 20 Q I assume your salary 21 is based to some extent on what you produce in terms of billing? 22 23 I object. MR. WAGNER: A Same objection. It's a straight salary, annual compensation, at 2297 ______________________ 13 9 1 2 this point. 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: 6 Object to the form of the question. 7 A That is not correct. 8 Q Do you know who J.E. Johnson was at Dow Chemical 9 10 Company back in 1969? A 11 12 There was a Julius Johnson who was a vice president for research, I think. 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: 17 let's mark this. 18 (Plaintiff's Exhibit 5 was marked for 19 20 So we have a record here, identification.) Q As part of Plaintiff's Exhibit 5, there's a 21 handwritten memorandum here, appears to be three 22 pages. 23 that? Do you recognize who may have prepared 2298 D-P39S' 140 1 MR. WAGNER: 2 question, calls for speculation. Object to the form of the 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 13 identification.) 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. 2 the chemical, Tordon? Are you familiar with 3 A In a general sense, 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 8 yes. Tordon? A 9 I couldn't name one of them, for you, no, I'm 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 14 Q Do you know whether either Kuron or Estron 15 that term. 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 2 Did you, yourself, Mr. Silverstein, ever contract 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: 12 Object to the form of the 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 anyprofessional organizations, 22 you told me what your educational background was, 23 but do you belong to any professional 2301 1 43 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 10 Have you held any positions with those 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 17 A 15 years ago. 18 '76, long ago was that? Let's see, I can tell you, 1975, '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. 23 Q That's it, I believe. Do you have a curriculum vitae that you maintain, 2302 14 4 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: 6 I haven't seen it. happy to get one for you. 7 MR. SCHULER: 8 to be produced. 9 any questions about it. 10 I think I asked for that If I don't have it, I can't ask MR. WAGNER: 11 I didn't recall that, frankly, but you may have. Have you got one here? 12 THE DEPONENT: 13 into this, I need to take a break. 14 MR. SCHULER: 15 (Recess.) 16 MR. SCHULER: 17 18 I'll be All right, if we're going That's fine. Okay, let's go back on the record. Q Let me show you this document that you handed me, 19 Mr. Silverstein. 20 with it, you can take it off, if you want. If that wasn't intended to go 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. 2 industrial hygiene services offered by Farlow 3 Environmental Engineers, Incorporated. 4 (Plaintiff's Exhibit 7 was marked for 5 6 identification.) Q 7 8 This is a letter describing the And this document here, if you would identify that, please, sir. 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 12 identification.) 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. 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 23 A And my question to you is what kind of My draft of the document you are holding said 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'. 3 done it occasionally, is more accurate. 4 Q I have 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: 9 Let me see it for a second, excuse me. 10 Now, the question said the word toxic 11 tort, and I object to the form. 12 doesn't say that. 13 A 14 The resume' I was going to say — MR. WAGNER: Listen to the question, and 15 I object to the form of the question. 16 undefined as to what toxic tort is. 17 Q 18 How long have you been a gun for hire, that's what I'm asking? 19 MR. WAGNER: 20 don't have to answer that one. 21 It's Q I object to the form. You 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 14 7 1 it here? 2 MR. WAGNER: 3 4 Object to the form of the question. 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: 16 Object to the form of the 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. 20 Q Would the bulk of your being involved with I don't remember. 21 attorneys have been on Dow Chemical Company's 22 behalf? 23 MR. WAGNER: Object to the form of the 2306 ___________________________________________________pq-jo3 148 1 question. 2 A Yes. 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: 8 9 question. A Was there a question? 10 (The requested material was read by the 11 reporter.) 12 MR. WAGNER: 13 Same objection, I object to the form. 14 A I don't know. 15 Q You don't know? 16 A I don't know. 17 18 Object to the form of the You asked, has that ever happened? That's a whole big universe. 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 21 22 23 A the past? Give me the question again, please. (The requested material was read by the reporter.) 2307 149 1 A I'd like to question the wording of the question. 2 You said, hired me. 3 attorney, to my knowledge, for anything. 4 Q I've never been paid by an 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: 11 12 question. A 13 14 Object to the form of the I have worked with attorneys representing the Dow Chemical Company exclusively. 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 Yes. 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: 5 Object to the form of the 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: 13 14 question, no predicate. A 15 16 Object to the form of the I don't even understand the question. It was confusing to me. 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. 23 study we referred to earlier of the 1964 workers Was that the 2309 O ' 3-VOfc 151 1 at Dow Chemical? 2 A Yes. 3 Q And your 4 A Yes. 5 Q Other than the case that we have at hand here, the name ison that study? 6 Moyer case, is your company, Farlow, being paid by 7 DowElanco or Dow Chemical in any other cases, 8 presently? 9 MR. WAGNER: 10 Object to the form of the question. 11 A I don't know. 12 Q No other 13 A None to my knowledge, 14 Q You mention, also, in your resume, here, that you ones that you're involved in? sir. 15 are a senior IH, I assume that's industrial 16 hygienist, for dioxin, and then in Agent Orange 17 investigations. 18 1964 incident that we've discussed here, or is 19 that some other position that you held at the 20 company? Is that in connection with the 21 A The former. 22 Q When you havedioxin here, and then parentheses, 23 agent orange, are you equating the two? 2310 D'SWo7’ 15 2 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 5 familiar than dioxin, presumably. 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: 18 Object to the form of the 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. 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: 12 What Object to the form of the 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 Yes. 18 Q Okay. 19 A In Midland. 20 Q And that encompassed,I assume, 21 the production many different types of chemicals? 22 A Yes. 23 Q Not just trichlorophenol or2,4,5-T or Silvex or 2312 of 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 12 13 I didn't understand your question. I missed a key word someplace. 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. 2 any of those documents here today? Do we have 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: 7 He didn't have any 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: 12 13 That's correct, it was a subpoena to him. 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 23 published on the epidemiological study? A I believe I do have a copy of that. 2314O'TMi/ 1 56 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: 6 that -- I asked -- I think I've got a copy. 7 THE DEPONENT: 8 Did you ask me if I had a copy of that? 9 MR. WAGNER: 10 THE DEPONENT: 11 Yes. No. I have it at home, but not here. 12 13 I didn't know that you had MR. WAGNER: Q I've got a copy. 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 17 It is a copy of a published article. You want the 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 23 (Plaintiff's Exhibit 9 was marked for 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. 10 down? 11 company? 12 A How is the company broken Are there other specific sections of the Well, there's an engineering group. That's pretty 13 much the rest of the company, except for 14 administration. 15 Q 16 How many people are in the industrial hygiene 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 21 22 23 training specialist. Q What are the names of the other two people involved? THE DEPONENT: Is this all pertinent? 2316 D' 5.^// 3 3 158 1 2 MR. SCHULER: A 3 4 Sure. Linda Jackowiac is the industrial hygienist. Russell Farlow is the training specialist. 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 9 A No. 10 Q Looking any stockin thecompany? atthis article we have 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. 16 you tell me, and you can look at this — 17 MR. WAGNER: 18 kind at the very end. 19 MR. SCHULER: 20 21 What kind? Can It says what That's what I'm looking for. Q I know you told me earlier, but usually it tells 22 you what the journal is at the top. 23 that on this. I don't see Can you tell me again what journal 2317 O' 159 1 2 this was published in? A 3 4 I believe it was the Journal of Occupational Medicine. Q 5 Can you tell me the year of publication 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: 17 characterizing, not calculating. 18 Q I think he said Okay, let me ask you to — it looks like a table 19 that you may have done. 20 take a look at that and tell me how you 21 characterize the exposure. Let me ask you to just 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 2 question. 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. 7 I could — 8 versus low exposure, in essence. 9 Q 10 And with all that information, I did the best I could in judging high Did you quantify it all or just put it in 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? A Dow Corning Corporation. Q Also in Midland? 13 A Yes. 14 Q How many hours, if you know, has your company 11 12 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. 22 Q Other than this article that's now been produced 23 15 maybe. 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 9 10 11 12 No. You asked if I have any documents pertaining to all that, right? Q That's correct. A The answer is no, I do not. 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 20 A Oh, boy, I have, in my files at home, a statement I made. I don't think it was even a deposition. 21 22 if it's involved with your materials or not, but 23 that's the only thing I can remember, and I do not I do not know what case. I do not know for sure 16 3 1 have a copy of that with me. 2 I mean at home in Midland, Michigan, because I 3 didn't move it down here. When I say at home, 4 Q A statement made in connection with litigation? 5 A Yes, but I have no recollection of what case, what 6 7 materials. Q deposition or — 8 9 When you say a statement, are you talking about a A I don't even know if it was a deposition, to be 10 honest with you. 11 made, and I was asked to review it for accuracy 12 and sign it if I agreed it was accurate. 13 I believe it was a statement 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. 18 product statement or not. 19 A I don't know if it's a work 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: 23 need to make a telephone call. I'll have to look at i t . 2322 D - a H i ”? 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? A Yes. Q And I've requested that be 11 12 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 — 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 23 THE DEPONENT: deposition. it's the I'm certain it's not a That, I know. 2323 O - 3-4^0 16 5 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 MR. SCHULER: I understand. copy? 8 9 Copies are 10 not an issue here. 11 itself. 12 witness on any items that are not produced that 13 fit the description of the subpoena that he may 14 have. 15 Q The issue is the statement, And I reserve the right to question this 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 22 23 caused by exposure to a pesticide, herbicide or other chemical or substance. Other than the 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 12 your opinion. Do you have any documents that fit that description? 13 A No, 14 Q Do you have any documents in your possession that sir. 15 you obtained from the defendants in this case or 16 their attorneys, through either this lawsuit or 17 other lawsuits? 18 A No, 19 Q Do you maintain files at home with regard to the sir. 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 20 21 MR. WAGNER: question. A No, I do not. 22 23 Object to the form of the MR.SCHULER: That's all I've got. Thank you. 2326 168 1 MR. LUTZ: 2 MR. WAGNER: 3 No questions. He'll read it. 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 16 9 1 STATE OF INDIANA 2 COUNTY OF MARION 3 I, ) ) ) ss: 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 10 That the foregoing deposition was taken on behalf of the Plaintiff; 11 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 at the 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 9 My Commission Expires: September 21, 1996 10 11 12 13 2329 1 UNITED STATES DISTRICT COURT 2 EASTERN DISTRICT OF ARKANSAS, WESTERN DIVISION 3 4 5 6 7 8 9 ) ) ) *Plaintiffs, ) ) -vs) ) THE DOW CHEMICAL COMPANY, ) et al., ) ) Defendants. ) _________________________________ ) JERRY KEISTER,et al., 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 î 16 For the Plaintiffs: MR. GARY DAVIS Gilreath & Associates P.O. Box 1270 Knoxville, TN 37901 (615) 637-2442 For the Defendant The Dow chemical Company: MR. STANLEY PIERCE Rivkin, Radler, Bayh, Hart & Kremer EAB Plaza West Tower - 11th Floor Uniondale, NY 11556 (516) 357-3000 17 18 19 20 21 22 23 24 MR. STEPHEN J. KRIGBAUM The Dow Chemical Company 2030 Willard H. Dow Center 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: MR. GARY DAVIS Gilreath & Associates P.O. Box 1270 Knoxville, TN 37901 (615) 637-2442 For the Defendant The Dow Chemical Company: MR. STANLEY PIERCE Rivkin, Radler, Bayh, Hart & Kremer EAB Plaza West Tower - 11th Floor Uniondale, NY 11556 (516) 357-3000 17 18 19 20 21 22 23 24 MR. STEPHEN J. KRIGBAUM The Dow Chemical Company 2030 Willard H. Dow Center 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: < MS.'LEEANN JONES Powell, Goldstein, Frazer & Murphy 400 Perimeter Center Terrace Suite 1050 Atlanta, GA 30346 (404) 399-2800 3 4 5 REPORTED BY: 6 7 J. Richard Loberg, RPR, CSR-2135 Certified Shorthand Reporter (517) 793-6672 1-800-878-6672 FAX: (517) 793-4290 8 9 —oOo— 10 11 TABLE OF CONTENTS 12 13 14 LAWRENCE G. SILVERSTEIN PAGE 15 16 17 3 78 90 Examination by Mr. Davis Examination by Ms. Jones Examination by Mr. Davis 18 MARKED 19 20 21 22 23 24 25 DepX#l DepX#2 DepX#2-A DepX#3 DepX#4 DepX#5 DepX#6 DepX#7 DepX#8 DepX#9 DepX#10 10 16 19 18 18 18 18 18 18 18 18 Letter (7-30-64) Memo (3-11-65) Report (9-28-64) Process Drawing Lab Notes Report (2-24-76) Letter (2-11-57) Memo (11-13-64) Memo (lr25-65> Memo (12-22-64) Report (10-9-64) GENERAL REPORTING SERVICE, INC. 2332 O- 3 1 EXHIBITS (Continued) •• 2 3 4 5 ** 6 ** 7 DepXlll DepX#12 DepX#13 DepX#14 DepX#15 DepX#16 DepX#17 DepX#18 DepX#19 DepX#20 DepX#21 DepX#22 MARKED Memo (3-10-65) Summary (2-10-70) Letter (4-10-70) Memo (5-4-65) Memo (8-16-66) Memo (8-16-66) Letter (1-17-67) (Not identified) Report - NaTCP (Not identified) Meeting Notes (8-25-64) Memo (3-29-65) 18 18 18 18 18 18 18 18 18 18 18 78 8 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. 23 questions today. 24 25 A I'm here to ask you some Have you been in a deposition before? Yes, sir. MR. PIERCE: Mr. Davis, would you indicate on •GENERAL REPORTING SERVICE, INC. 2333 V •5.^30 4 the record why we're starting at this time, please? 1 MR. DAVIS: 2 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. MR. PIERCE: 7 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 MR. DAVIS: I don't understand what's going on MS. JONES: I think it has something to do minute. 14 15 here. 16 17 with your speaker because it's cutting in and out. 18 19 MR. DAVIS: 20 we got a speaker phone here. 21 MS. JONES: Yes, I can hear you fine now. 22 MR. DAVIS: We'll go on. 23 Q I don't know what to do, LeeAnn, (By Mr. Davis, continuing): Can you hear now? 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. 5 A Lawrence Gordon Silverstein. 6 Q And where do you live? 7 A Midland, Michigan. 8 Q Okay. 9 A 5409 Mason Street. Thanks. Can you state your full name, please? Can you give me your address, please? 10 MS. JONES: 11 Gary, you guys are gone again. (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. 15 A Yes, sir. 16 Q And who are you employed with? 17 A The Dow Corning Corporation, Midland, Michigan. 18 Q Okay. 19 A Ten years, round figures. 20 Q Before you were with the Dow Coming Corporation were Are you currently employed? And how long have you been with Dow Corning? you with The Dow Chemical Company? 21 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: 6 question. Objection to the form of the 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? 10 major production facility of The Dow Chemical Company? MR. PIERCE: 11 A I don't know for sure. MR. DAVIS: 14 15 16 Objection to the form of the question. 12 13 Is that the I was told it was at that time. Off the record just a second. (Conference off the record.) 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. 20 Q How about at the time you were working there? 21 A I don't remember. 22 Q Thousands? MR. PIERCE: 23 question. 24 25 Not at this time. Q Objection to the form of the The man answered he doesn't know. Was it in the thousands* as far as you know? GENERAL REPORTING SERVICE, INC. 2336 P-24 3 3 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 responsibility for when you started in 1955? 5 MR. PIERCE: 6 7 Objection to the form of the 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? MR. PIERCE: 12 Objection to the form. No foundation. 13 14 A To the best of my recollection, about 1964. 15 Q Okay. You were aware that Dow had been making trichlorophenol all the way back to 1946, weren't you? 16 MR. PIERCE: 17 Objection to the form of the question. 18 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 to 1964? 22 MR. PIERCE: 23 question. 24 25 Objection to the form of the 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 answered. 5 6 A The best of my recollection, yes. 7 Q And that Dow was also making 2,4-D? 8 A Yes. MR. PIERCE: 9 Objection to the form of the question, if that is a question. 10 MR. DAVIS: 11 Let's do one thing for the judge 12 right now which is I think I'm entitled to ask leading 13 questions here. 14 employee of The Dow Chemical Company, now works for Dow 15 Corning. 16 have no foundation. 17 MR. PIERCE: It's a witness who has been an If your objections are to leading then they 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 Nam war? 21 22 You're aware that Dow made Agent Orange during the Viet A No, sir. MR. PIERCE: 23 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. GENERAL REPORTING SERVICE, INC. 2338 I 9 1 2 never heard the term until long after. Q Dow's 2,4,5-T and Dow's 2,4-D were blended to make Agent Orange as far as you know? 3 4 MR. PIERCE: Objection to the form of the 5 question. 6 man has answered as to his knowledge. Not only leading, but argumentative. The 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. 11 was the 199 Building? 12 MR. PIERCE: 13 give us a time frame? Objection to the form. What Want to 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. 19 Q What were those? 20 A Aniline and trichlorophenol. 21 Q And at the time that you became involved with the 199 22 Two major products were made there. 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: question. Objection to the fora of the 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 Davis, if you could show me. 1 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. 5 you not? 6 A Yes, sir. 7 Q And then it says: Larry S.M 8 You were known by Larry, were "Alex, please return this to me. Is that the way you read this? 9 A Yes, sir. 10 Q And you're Larry S ., is that right? MR. PIERCE: 11 12 Q Objection to the form. You presume that this was yours, is that correct? MR. PIERCE: 13 Why should he presume it's his? 14 He gave you the answer to your question. 15 and answer it. MR. DAVIS: 16 But go ahead He did until you suggested otherwise. 17 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 5 That was your understanding of how the process worked, 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 — 11 reactor which was called a caustic insoluble oil? 12 you recall that? an oil material from the trichlorophenol 13 A I remember the term, yes. 14 Q Do you know if it was also called a non-saponifiable 15 Do 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 MR. DAVIS: Yes. 21 here? 22 23 A knowledge, my understanding. 24 25 It was a waste stream from the process that was my Q And do you remember what Dow would do with this oil GENERAL REPORTING SERVICE, INC. 2342 p. aH 13 1 would be to separate it in the 199 Building from the 2 trichlorophenol product and incinerate it? 3 MR. PIERCE: question. 4 Objection to the form of the 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? 10 don't you? 11 12 MR. PIERCE: A 13 14 You recall that, Continue the objection. I'm not sure I hear a question. Are you asking me to verify that? Q 15 I'm asking you if that statement is a correct 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? 2 understand what you are really asking this witness to 3 do. 4 Q 5 I mean I don't If you don't recall you may use Exhibit 1 to refresh 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: 20 Objection to the form of the 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 incident in 1964, is that correct? 23 MR. PIERCE: 24 25 Q The document speaks for itself. 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: already testified he was not involved in 1963. 6 7 I believe that the witness has 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? MR. PIERCE: 10 11 Objection to the form of the 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. 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: 20 21 24 25 You Objection to the form of the question. A My recollection is the process changes were believed to have contributed to the thing, yes. 22 23 But we'll try to persevere. Q Okay. And you know that pushing production to the limit had something to do with it as well? 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 5 6 7 8 HR. PIERCE: A Objection to the form. I read it in the memo. Hy recollection was it was later than that but that shows how memory goes. HR. DAVIS: Exhibit 2. Let me go ahead and introduce Let's mark this. 9 (DepX#2 marked*.) 10 MR. DAVIS: You want to look at it? 11 MR. PIERCE: Sure. 12 two documents clipped together. 13 look and make sure? 14 you want it or — 15 MR. DAVIS: Gary, there appear to be You want to take a I don't know if that's the way 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: 20 21 I just want to point out you seem to have Exhibit 1 attached to it as well. 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. 25 Mr. Silverstein. So let me just show this to 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. 3 that in the form that you wish to present it to us? 4 MR. DAVIS: That is correct. That appears to be the form in which this document was copied. 5 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: 12 13 is Objection to the form. it's really confusing. Q But go ahead. You're the author of this document? 14 15 I think MR. PIERCE: By "this document", what do you MR. DAVIS: I one I just described that says mean? 16 17 "The Chloracne Problem, Biochem's Contribution", dated 18 3-11 '65. 19 Q 20 You're the author of that, is that correct? MR. PIERCE: 21 Just to clarify, you don't mean the entire exhibit, is that correct? m 22 MR. DAVIS: I thought we made that clear. 23 MR. PIERCE: Okay. 24 25 A It looks like something I remember writing but I can't 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 documents in preparation for this deposition? 4 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 10 I will need a few minutes to read through it because again I did not look at every word. I would like to request a restroom break. 11 12 MR. DAVIS: 13 (DepX#3 through DepX#21 marked.) 14 (Recess) 15 16 MR. DAVIS: Q Certainly. Let's go back on the record. (By Mr. Davis, continuing): Mr. Silverstein, I learned 17 how to pronounce your name correctly during the break. 18 I apologize. Have you had an opportunity to review Exhibit 2? 19 20 A Yes, sir. 21 Q Okay. MR. PIERCE: 22 25 Objection to the form. There are three, at least three different documents. 23 24 And you once again were the author of Exhibit 2? Q Let's clarify that now for the record. have your copy of Exhibit 2. Let me just 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 been marked as Exhibit 1? 4 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. (DepX#2-A markfed.) 14 15 Q Exhibit 2-A is titled "Chloracne Status Report - July 16 to September, 1964", from A. F. Lueck — 17 you say it? 18 A Yes, sir. 19 Q L-u-e-c-k. September 28th, 1964. 20 that with you. 21 about Exhibit 2. 22 A is that how We'll just leave Right now let me ask you first of all What was biochem that's referred to? It was the biochemical research laboratory of The Dow Chemical Company. 23 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. 8 A Oh, yes. 9 Q And — 10 A Or try harder. 11 Q What do you recall about how that chloracne looked in If you can maybe speak up a little bit? I'm sorry. I'll try better. 12 the workers who worked in the plant, in the 199 13 Building? MR. PIERCE: 14 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 20 MR. PIERCE: A Objection to the form. I don't remember other than what's in the document. Somewhere in the 40 range, I think. 21 22 % Q Okay. Now, Dow had had experience with chloracne before, is that right, before 1964? 23 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? 7 Q Okay. I lost track of it. The question was Dow knew as early as 1941 that certain chlorinated organic compounds caused chloracne? 8 MR. PIERCE: 9 Are you asking him does he recall that now or ~ 10 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 16 MR. PIERCE: A Sorry. Objection. 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 2 HR. DAVIS: A 3 Or any time that it was used. I'm not a toxicologist but I will describe my 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. 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 14 15 By folliculitis you mean a skin reaction, is that what you were looking for? A 16 17 And The hair follicles inside the rabbit's ear where the material had been placed were affected, yes. 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? 21 MR. PIERCE: 22 23 Objection to the form of the question. 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 i ! 23 1 Q Let me ask you if you have ever seen Exhibit 4 before which ve have previously marked. 2 3 MR. PIERCE: first page is at least to me illegible but — 4 5 I just like to indicate that the Q Appears to be a — some sort of handwritten notes from 6 a laboratory and if you can — 7 unreadable please look at the rest? MR. PIERCE: 8 if the first page is Let me just object to the characterization but please, go ahead and read it. 9 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 — 13 page 3 of Exhibit 2? I'm sorry, 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. 21 A I can hear you from here, sir, if you want to keep strike that. going. 22 23 And you've — 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 knowing in 1955 that the Germans had * 2 had problems with chloracne in the production of 3 trichlorophenol? 4 HR. PIERCE: 5 Objection to the form of the 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 10 don't recall it. 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: 14 15 Objection to the form and the witness has already testified he has no recall. A 16 What I recall is they proposed that this may be it. 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 question. 20 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 caustic insoluble oils since 1945, is that right? 24 25 A That's what I was told. Remember, I wasn't there until GENERAL REPORTING SERVICE, INC. 2354 O' 25 '55. 1 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: 6 Objection to the form of the 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, yes. 22 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. Q Okay. 3 I have been trying. Can I ask you the same question about Exhibit 2, 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: question. 10 11 Objection to the form of the A And the question's a bit vague because there are more than one such material. 12 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. 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. 21 Q Okay. What I'm I have used it before. 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 2 question. A culprit. 3 4 My recollection is we determined it was the primary 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 laboratory? « 7 MS. JONES: Object to that question. 8 MR. PIERCE: Objection. 9 witness's scope of knowledge. 10 it to the best of your ability. 11 A 12 13 This is outside this But go ahead and answer Once again I'm not a toxicologist but I did hear that, certainly. Q 14 15 16 And if you'll please turn to Exhibit 5, page 8. also wrote that on page 8 of Exhibit 5, correct? MS. JONES: Gary, could you tell me what Exhibit 5 is? 17 18 MR. DAVIS: Sure. Off the record. (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: 22 the document speaks for itself. 23 does. 24 25 You I'd just like to object in that If it says that it And could we have the question read back, please? (Requested portion read back.) -GENERAL REPORTING SERVICE, INC. 2357 28 MR. PIERCE: 1 I'd like to object to the 2 characterization of what the document states. 3 it is taken out of context and further that the document 4 speaks for itself. 5 Q 6 Okay. I think You may answer the question about whether you 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 Building 199 in the trichlorophenol process? 16 17 Were you appointed as a full-time safety person for A Not at that time. MR. PIERCE: 18 19 Objection to the form of the question. 20 A Not at that time. 21 Q When were you appointed as such? 22 A Sometime later. 23 Q Okay. I don't remember exactly. 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 % MR. PIERCE: 1 2 Q In what time frame? 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? MR. PIERCE: What do you mean by is this the 21 MR. DAVIS : The letter he just referred to. 22 MR. PIERCE: Are you asking him if he has seen 19 20 23 letter? 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 34 2 was the Dow process in use at that time in 1964-65? * HR. PIERCE: You mean is this document the 3 Dow process, number 3? 1 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? MR. PIERCE: 17 of the term "caustic insoluble oils". 18 19 A 20 21 Objection to the form and the use In conjunction with my industrial hygiene efforts a nu m b er Q of tests were run on many different things, yes. Were some of those run on the caustic insoluble oils? 22 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: 2 question, honestly. 3 Q I'm sorry, but that's not a clear 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? HR. PIERCE: 7 8 9 question. A To my recollection there was an instance in which that happened, yes. 10 11 Objection to the form of the Q Did Dow consider shutting down the Building 199 process in the 1964 time frame? 12 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 appointed full-time safety officer for that plant? 15 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? 3 you sample? 4 MR. PIERCE: What kinds of surfaces would Objection to the form. Could we have a time frame here? 5 6 Q In the 1964-65 time frame. 7 A Primarily work surfaces that might be contacted by 8 9 employees. Q They were the focal point of the wipe test. 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 — another type of test done on those 20 21 A 24 25 Eventually in a machine. wipe samples? An analytical method was developed and used. 22 23 at a later time frame was there Q And was the purpose of the wipe test to determine the levels of TCBD or dioxin on surfaces in the plant? MR. PIERCE: Objection to the form of the GENERAL REPORTING SERVICE, INC. 2366 ■Q-9«b3 37 1 2 question. 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. 5 along we were able to identify the specific material we 6 were looking for, yes. 7 Q When the analytical method came 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 Q A Well, that's a very broad question. I found all kinds of results, you know, good and bad. 16 17 What did you find when you took those wipe samples and had them analyzed in 1964? 14 15 I don't know what the situation is now. 12 13 Initially, yes. Q Did you find that the Building 199 was extensively contaminated with the compound that causes chloracne? 18 MR. PIERCE: 19 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 samples in the 199 Building. 24 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 14 That's my recollection. Q 15 Okay. Were there workers wiping the surfaces at the same time or — 16 MR. PIERCE: 17 Objection to the form of the 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 (Recess) 1 2 MR. PIERCE: 3 4 Okay. I believe the witness has completed his review. Q (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: 10 Objection to the vagueness of the 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 14 them. Q 15 16 Do they refresh your recollection in any way on the steps that were taken in 1964 and '65? 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. 3 feet by 180 feet washed down with detergent and painted 4 with aluminum." 5 It says: "November 13th - Reactor room 100 Is that the clean-up that you were describing? HR. PIERCE: 6 Objection to the form that you 7 are reading from a document not identified. 8 ahead and answer the question. But go 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? you? 13 14 Does that ring a bell to 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 reactor? 18 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? MR. PIERCE: 24 25 question. Objection to the form of the 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. 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 9 shift and required any time a person had to get into a % full suit — that's immediately after the job, excuse 10 me. 11 Q So you required showers twice a day «— HR. PIERCE: 12 13 Q Objection to the form. for the workers that worked with trichlorophenol? That is not — that's a mischaracterization of what he just indicated to you. 15 16 — MR. PIERCE: 14 And in addition extreme Q I am asking another question. You required showers 17 twice a day for the workers that worked with 18 trichlorophenol? MR. PIERCE: 19 well, go ahead. 20 21 A Objection to the form. I think — I'm sorry. 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- 2 Precautions For Trichlaarcphenal Operators, I*. an17 51 sir. 1 2 Q When did you first write those procedures? 3 A Latter part of the 1960's is my recollection. 4 Q Okay. 5 Would you know whether or not Exhibit 12 is the 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. 9 hazards of dioxin to the hazards of radioactive 10 materials? MR. PIERCE: 11 Do you liken the 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 it from outside Dow Chemical or within, either. 20 21 Q You don't know of any particular persons who it was sent to then? 22 23 A I do not recall any specific recipiants, no, sir. 24 Q Okay. 25 Why would you recommend that persons using dioxin in a laboratory throw away plastic gloves • GENERAL REPORTING SERVICE, INC. 2381 0-^47^ 52 without contacting the exterior surfaces of the gloves? 1 MR. PIERCE: 2 3 Are you referring now to the document or — 4 Q Yes. 5 A Because unless employees are instructed on a proper Referring to Exhibit 12. 6 method of removing contaminated gloves they unwittingly 7 may contact the contaminated outside. 8 show them how to do it properly. 9 Q You have to What type of gloves did you require the employees in the trichlorophenol process to wear? 10 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 19 20 What about the employees that were actually handling the caustic insoluble oils in some fashion? A Probably a specific rubber glove that we had in the plant. 21 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 i ! 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 8 9 What was the purpose of requiring such a breathing hood? 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 caused the chloracne, the dioxin in the process? 13 MR. PIERCE: 14 15 Objection to the form. Asked and 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: 21 any particular time period. Objection if that's not limited to 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 5 Okay. Do you recall what the employees would then do 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. 10 Q Was that true during the whole time that you were the I safety officer in the trichlorophenol process? 11 J 12 A Yes, to the best of my recollection. 13 Q Why did you recommend in Exhibit 12 that clothing known I 14 to be contaminated should be disposed of with the 15 precautions described under disposal of wastes? 16 MR. PIERCE: 17 j t Is that supposed to be a direct quote from the document? 18 MR. DAVIS: j j That is a direct quote. 19 A May I read the entire part there? 20 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? 6 A From my memory it's basically assuring that people j 7 transporting the contaminated laundry are protected by 8 having it inside clean bags — 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. 12 after the equipment — 13 washed that the equipment itself is rinsed. 14 Q And that after the materials have been Okay. 15 MR. DAVIS: 16 17 clean on the outside. Let's take a short break. (Recess) Q (By Mr. Davis, continuing): Let's go back and let 18 me ask you to look at what's been marked as Exhibit 21. 19 It's very difficult to read. 20 copy. i ! j MR. DAVIS: 22 23 25 i | I just want to ask you to see if you can i j identify it. 21 24 I apologize for the poor Off the record. i i (Conference off the record.) Q If you can just attempt to review this document, Mr. Silverstein, and I have a couple questions I wanted to GENERAL REPORTING SERVICE, INC. \ 2385 D-.W«2' 56 ask you about It. 1 MR. PIERCE: 2 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 — 22 there a question? 23 A 24 25 is I did not see a table or chart of process changes as such. Q What is the table that's on the third page or chart on GENERAL REPORTING SERVICE, INC. 2386 57 the third page? 1 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. 8 page 1 of Exhibit 21 it says: 9 a chronological chart of the process changes, et 10 cetera, relating such changes to the chloracne problem." "L. Silverstein present Do you know if that is any earlier document that 11 we have looked at? 12 13 If you notice on A 14 I don't know to be honest with you. I didn't see a 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 — 20 were tested on the bellies of rabbits, I believe. MR. PIERCE: 21 24 Objection. The document speaks for itself. 22 23 and also there is some that A The first three tables appear to be process materials that were tested on animals. * The next one is wipe test for 199 which are not process samples, of course, and i GENERAL REPORTING SERVICE, INC. 2387 58 1 2 then the last one I didn't look at again. 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: 6 The document speaks for itself. Once again I renew my objection. 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? MR. PIERCE: 12 13 14 no foundation. A 15 16 Objection to the form. There is Answer to the best of your ability. I wasn't involved in that. I don't remember to be honest with you. Q 17 Do you know if Dow ever purchased trichlorophenol from other suppliers? 18 A I believe they did. 19 Q Was it during the time that the Dow process was temporarily shut down? 20 MR. PIERCE: 21 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. MR. PIERCE: 8 I will read it. "Hazard of Monsanto-T Acid" appears to be the title. 9 10 MS. JONES: I couldn't hear it. 11 MR. PIERCE: "Hazard of Monsanto-T Acid". 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, LeeAnn, also has a legibility problem. 16 17 Q 18 Can you attempt to read the second page for the record, Mr. Silverstein? 19 MR. PIERCE: If you can. 20 A Just the sentence? 21 Q Yes. 22 A "I believe Dow has a definite obligation to advise 23 24 25 And Riverdale and Woodbury of the problem immediately." Q Okay. Can you tell the jury what problem that you were referring to? GENERAL REPORTING SERVICE, INC. 2389 60 1 A with acnegen. 2 3 Well, as stated in the memo, some material contaminated Q This was Monsanto trichlorophenol that was contaminated with the acnegen? 4 5 MR. PIERCE: characterization. 6 7 Objection to the form and Q Is that correct? 8 MR. PIERCE: 9 Answer it to the best of your 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 about 1967. 1 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: 8 9 Are you asking hist about his current recollection or — 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"? 18 statement of testimony but the document, is that 19 correct? You are not dealing with his previous 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 4 to even there in that document says as I remember it. Q Okay. We have other documents as veil that ve can 5 refer to if that's a question. 6 ask you is how Dow went about developing the new 7 process for production of trichlorophenol that was 8 commenced in approximately 1966? MR. PIERCE: 9 But what I want to Objection to the form, it's 10 outside of this witness's knowledge. 11 the best of your ability. 12 A It was a combination of'some Dow research and purchase of some technical information from another company. 13 14 But answer it to 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: Mr. Silverstein, could I ask you to speak up a little bit? 20 21 Excuse me. 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 MR. PIERCE: I am moving it over now, LeeAnn. 24 25 speaker? GENERAL REPORTING SERVICE, INC. 2392 63 1 A 2 My recollection is that Mr. A1 Lueck and a Mr. Walt Trapp were the other members of the team. 3 Q And you visited aFrench 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 chemical company? 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: question. 17 18 A Object to the form of the You can answer. 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 health hazards of dioxin or TCBD? 22 MR. PIERCE: 23 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 2 My recollection is that Mr. A1 Lueck and a Mr. Walt Trapp were the other members of the team. 3 Q And you visited aFrench 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 chemical company? 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? MR. PIERCE: 16 question. 17 18 A Object to the form of the You can answer. 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 22 What did you learn about Boehringer's knowledge of the health hazards of dioxin or TCBD? MR. PIERCE: 23 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. Q Okay. I'm sorry. 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 capable of answering it* ~ 6 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: 18 Objection to the form and 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 22 close to you. On page 11. 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...... 65 1 is on that document? 2 MR. DAVIS: i Yes. 3 A That's what it says. 4 Q And you wrote this document? 5 A I believe so. 6 Q What happened to the old plant that had been shut down in 1965. 7 8 9 MR. PIERCE: A 10 Objection to the form. At some time after shutdown it was dismantled and disposed of. 11 Q How was it dismantled? 12 A Very carefully. 13 Q And how was it disposed 14 A I don't really have first-hand knowledge of that to be 15 16 With great precautions. honest with you. Q 17 Do you know if the parts were buried? MR. PIERCE: 18 A I don't know for sure. 19 Q What do you recall? 20 21 of? Objection. Asked and answered. I mean you obviously recall something about that. A Oh, yes, but the recollection is really, you know, not 22 specific, vague. In general, that some of the 23 equipment was cleaned up and salvaged and others sent 24 to disposal. 25 not firm but group.in-house that made the decisions on Dow had its own waste disposal firm — GENERAL REPORTING SERVICE,-INC. 0- 66 best disposal methods. 1 2 Q 3 4 And when you say that it was dismantled very carefully with great precautions, what precautions were taken? 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 j Were there specific precautions as to protective equipment? 9 10 A I honestly don't know that at this point. 11 Q Do you recall anything about the new process that was I 12 • commenced in approximately 1966? 13 14 MR. PIERCE: Q MR. PIERCE: A 17 18 Asked and answered. As far as the reaction steps go? 15 16 Objection. Continue the objection. I remember nothing of the technology of the process itself, no. Q 19 Okay. You do recall that the levels of dioxin in the new process were less though, 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 added to the reaction vessel to control the temperature 23 and pressure of the reaction? A Not at all. GENERAL REPORTING SERVICE, INC. 2397 j j 67 1 HR. PIERCE: Objection to the form of the 2 question and it's completely vague. 3 was your answer? I'm sorry, what 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. 8 that? 9 A What was your position after 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 16 17 I had essentially no involvement after I had moved to the other — Q the new project. Might you be a little vague about the dates when you 18 moved to the other project? 19 establish what your involvement was. 20 A I'm pretty sure — 21 MR. PIERCE: A Go ahead. I am pretty sure that I moved into the solvents project in 1967. 24 25 I'd like to make an objection. The question was asked ¿rnd answered. 22 23 I'm just trying to Q Okay. I just want to show you what's previously been GENERAL REPORTING SERVICE, INC. 2398 D•W'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. 10 authored, Mr. Silverstein? Is this a copy that you % 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 — 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. actually a letter that's been marked 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 — 25 tetrabromodioxin and wrote and requested the sample that he had made or was doing something with GENERAL REPORTING SERVICE, INC. 2399 69 1 that's described there. 2 only say that he was an*academic in my recollection. 3 have no idea what he was doing with the stuff. 4 Q But I would — you know, could 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. 19 A 20 But answer the question. I recall some — oh, you know, knowing that that had 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 I 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 10 11 I have no first-hand knowledge of that. I heard it, yes. Q Let me refer you to Exhibit 5, an insert directly 12 after page 13 of Exhibit 5. 13 the human testing that we have been referring to, 14 correct? 15 MR. PIERCE: 16 In Exhibit 5 you discuss If you ask him — are you asking him if that's what the document indicates? 17 MR. DAVIS: 18 wrote in Exhibit 5. I am asking him if that's what he 19 A It looks like something I wrote, yes, sir. 20 Q Concerning human testing of these materials on 21 22 prisoners? 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. 25 prisoner not be a volunteer. Nor may a / GENERAL REPORTING SERVICE, INC. 2401 71 1 Q You understood or at least you heard these were prisoners that were tested, correct? 2 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: 9 10 Objection to the form of the question. A 11 Well, I learned in the course of my involvement that 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. 24 those other effects that you're aware of? 25 A What are 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 4 Are you aware of any other effects as we sit here today 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 25 Q I'll be more specific if Mr. Pierce wants me to be. That the Dow tests on the materials from the i GENERAL REPORTING SERVICE, INC. 2403 Q, £ 5 o o | i 73 trichlorophenol process that contained dioxin also In 1 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? MR. PIERCE: 5 6 A I was aware of this. MS. JONES: 7 8 A A I couldn't — I was aware of this, LeeAnn. 9 10 Continue the objection. MS. JONES: Was? MS. JONES: Thank you. Yes. 11 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 as Exhibit 19? 3 4 And you might read the title of it, Stanley, since you got it there. 5 6 HR. PIERCE: It has a cover page saying "NaTCP Solution IWD". 7 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 the trichlorophenol reactor, had a ruptured disk? 19 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 friend of mine. 2 3 The only one I recall is Emil Christofano who is a Q What communications have you had with Mr. Christofano 4 concerning trichlorophenol or phenyoxy herbicides or 5 dioxin? 6 7 A 10 11 Objection to the form of the MS. JONES: I object in that it's vague. question. 8 9 MR. PIERCE: I have never discussed these matters with him to my recollection. 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: 19 question and specifically to the term he determined. 20 21 Objection to the form of the MS. JONES: A I object also. 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 hygiene. 1 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: 8 question. 9 determined. Objection to the form of the Also object to the statement that he 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: 18 19 question. A 20 21 Not to my knowledge based on what I recall of our information. Q j Did you test the 2,4,5-T processing area for the presence of thematerials thatcausedchloracne? 22 23 Objection to the form of the A j I believe I did, yes. 24 MR. DAVIS: 25 MR. PIERCE: That's Okay. all I have. When do you want to start j i i GENERAL REPORTING SERVICE, INC. 2407 i |i 77 1 again? 2 MS. JONES: 3 (Conference off the record.) 4 5 Was that all that Gary had? MS. JONES: I have just a couple of documents. 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. 8 it's something you really need to be here for. 9 MS. JONES: I mean I have got a document dated March 10 29, 1965. 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: It is a memo prepared by Mr. Silverstein to 15 that one. 16 this is not it. 17 else? 18 Let me — Okay. I think we have introduced it was difficult to read. No, I don't know that I have that. What j 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. 21 MR. DAVIS: i 22 23 Going back to that first one, LeeAnn, was that with regard to the meeting in Midland? MS. JONES:Yes. MR. DAVIS: 3-24-65 meeting. Okay. I may have that. I didn't i \ j j i i I | realize it was from Mr. Silverstein. \ GENERALREPORTING SERVICE, INC. j 1 j | i i 78 MS. JONES: 1 It is part of the documents you guys produced at Dr. Ratalik's deposition. 2 3 MR. PIERCE: Who is the author of the '67 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 memo? 4 on the 1967 one or is he the author? 8 MS. JONES: 9 10 have got. I can't tell from the copy that I 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. EXAMINATION 18 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. MR. PIERCE: 23 over one of them. 24 25 Well, obviously he has not looked 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. 10 A Yes, ma'am. 11 Q Hr. Silverstein, the exhibit that has been marked as You ready? 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 document? 22 % MR. PIERCE: 23 24 25 A If you recall? I believe I was asked to write a summary of the meeting, LeeAnn. GENERAL REPORTING SERVICE, INC. 2410 0 9.501 - 80 1 Q 2 I'd like to direct your attention to page 2 of that document to help refresh your recollection. 3 MR. PIERCE: 4 witness needs his recollection refreshed. 5 6 There is no indication the MS. JONES: Q 7 I'm not suggesting that he does. Do you recall a Dr. Holder giving a report at that 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 11 report? A 12 13 He reported on the medical findings and treatment of the Dow employees. 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 19 those workers? A What do you mean by clinical studies, ma'am? 20 21 I'm out of my field. 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 tests? 1 2 A 3 4 Yes, ma'am. I believe I was referring to blood sampling. 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: 11 12 portions of the document. Q 13 14 A Did you report that in that March 29th memo? Yes, ma'am, to the best of my recollection that's what I wrote. Q 17 18 You may answer. Mr. Silverstein, you can go ahead and answer the question. 15 16 Let me object to the reading of Did you recall those liver biopsies having been done or that particular liver biopsy? A I remember a single liver biopsy being available to us at that time, yes. 19 20 Q Do you remember what the result of that biopsy was? 21 A I remember being told that there was no liver injury evidence. 22 23 Q And did the person on whom the liver biopsy was performed have a case of chloracne? 24 A According to Dr. Holder, yes. I never knew or met the GENERAL REPORTING SERVICE, INC. 2412 82 patient. 1 % 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? HR. DAVIS: 5 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? MR. DAVIS: 14 Q Could you go ahead and answer, do you recall whether you reported that he mentioned that at the meeting? 17 18 The document speaks for itself. 15 16 Object. 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. 22 Q Do you also recall that there were no other significant findings reported by Dr. Holder? 23 MR. DAVIS: 24 25 But I am a layman. A Obj ection. 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. 7 Q That's the number I remember. 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 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: of that memo was? Are you asking his independent recollection now or what the document indicates? 16 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 21 Q Did you know in about 1970 at the time you prepared History". 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 knew. 2 3 I believe that's what I knew at the time or thought I 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. 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 Do you recall anything, any 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: question. 24 25 Objection to the form of the 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 exposure of Dow employees to the materials. Q Were those all instituted after the 1964 incident of 2 3 4 5 Dow workers coming down with chloracne? A 6 7 Some of them were in force before that to my — to the best of my recollection, LeeAnn. Q If you will bear with me for just a minute while I go 8 back through my notes. 9 and 1965 did you know anything about the Hercules 10 process for manufacturing 2,4,5-T? Hr. Silverstein, back in 1964 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 19 20 In the course of my involvement in that Dow tested some Hercules' products, that's the only knowledge I have. 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. area of expertise. You are way outside of my 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: 6 7 Objection to the form and no foundation. 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 don't remember when. 11 12 I remember becoming aware of that at sometime but I Q 13 Do you remember ever learning that BASF experienced 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 first learned that? 22 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 workers? 1 2 A I don't remember knowledge on Diamond Alkali, no. 3 4 I'm thinking. Q Do you recall ever learning that Shone Polunc had a problem with chloracne among its workers? 5 6 A No, ma'am. 7 Q Have you learned since leaving Dow that Shone Polunc had a problem with chloracne among its workers? 8 9 A No. You were the first to advise me. MS. PIESCE: 10 11 Q A 14 15 I wouldn't call that advising. Do you recall ever learning whether Phillips Dufar had a problem with chloracne among its workers? 12 13 I didn't hear that name until I left Dow. That name strikes a familiar bell in my recollection but only the name, I don't remember details. 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 24 25 MS. PIESCE: Objection to the form of the MS. DAVIS: I join. question. 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? MR. PIERCE: 6 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. 12 steps but I'd ask an engineer to go look for me in that 13 instance. 14 Q That would include process 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 20 21 hygiene procedures, definitely. Q Were you aware in the 1960's that Hercules did not have any problem with chloracne at its plants? 22 MR. DAVIS: 23 Objection. Leading and lacks foundation. 24 25 I would have been very interested in their industrial A I don't remember. % GENERAL REPORTING SERVICE, INC. 2420 90 1 Q A I don't remember having a knowledge either way on that one, LeeAnn. 4 5 Were you aware whether or not Hercules had a chloracne problem at its plant? 2 3 Strike it. 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? MR. PIERCE: 9 Completely speculative. 10 MR. DAVIS: 11 12 Objection. A I join. I believe so. 13 MS. JONES: That's all I have. 14 MR. PIERCE: Thank you. 15 MR. DAVIS: One follow-up. We'll see you later. EXAMINATION 16 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. 21 at that meeting, Mr. Silverstein? Were you present 22 A Yes, sir. 23 Q Was Mr. C. L. Dunn from Hercules present at that 24 25 meeting? 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 recollection? 2 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 7 Does Exhibit 22 say that C. L. Dunn was present at the meeting? 8 A Yes. 9 Q And you wrote Exhibit 22 shortly after that meeting, % correct? 10 11 A Yes, sir. 12 Q And does Exhibit 22 also show that Dr. John Frawley 13 14 from Hercules was present at that meeting? A The document showsthat, yes, sir. 15 MR. DAVIS: That's all I have. 16 MR. PIERCE: Okay. 17 MS. JONES: Okay. LeeAnn? 18 (Deposition concluded.) 19 -oOo- 20 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. I also certify that prior to taking this deposition 8 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: 20 9-3-91 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. £h-«P:C 2425 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 Inhibition in Chinese Hamster 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 Caddell. (Dr. Marvin Legator appears on two of the tapes). Mike 8. 1/88: USDA Publication from the Pacific Northwest Region of 2426 O •<5.^3 — z.- 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 of 2,4-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 2,4-D and 2,4,5-T attack. the specific genetic centers that 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 _ ^2 _ 2427 Q -3 6»c9>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, * y - 2428 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 Oí crr C\i d> co Tí* A Ó o ¿ 9 1 - 0 '***’ ___ E£iZ I 0 ~ í - 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* a n d 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: C ourtney , 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 aeent. w « 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 99°0 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 A nalysis of A nalytical and T echnical G rade Samples of 2,4,5-T. A nalyses S upplied by D ow C hemical C ompany . Quantity of impurities Impurities 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 Technical“ Analytical 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 398 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. Species Compound M aternal M aternal weight gain (g) X SD liver/body weight x 100 X SD a 50 100 150 a 100 1 3 a 100 100 125 100 1 1 a 100 3 a 100 3 12 7 3 4 9 9 9 10 8 10 10 9 10 24 II 9 24 15 7 6.6 6.6 7.5 51.7 8.8 9.6 13.6 12.4 8.4 10.7 11.6 12.9 11.8 26.1 27.0 27.0 10.8 15.9 5.3 1.35 1.26 1.00 0.91 1.02 0.73* 1.07 0.96 1.09 0.85* 0.86* 0.71* 0.78* 0.85 0.67* 0.89 0.99 0.75* 1.05 0.09 0.07 0.07 0.14 0.20 0.16 0.24 0.24 0.20 0.13 0.17 0.25 0.11 0.11 0.10 0.13 0.09 0.12 0.16 2.25 2.87. 4.76 4.14 2.92 2.97 2.44 2.80 3.44 4.46 3.17 3.75 3.75 3.82 2.37 3.97 3.35 1.67* 3.25 2.00 1.84 0.89 2.45 1.54 1.76 1.93 1.85 1.86 2.22 2.85 4.16 1.85 1.68 >2.15 '1.89 1.48 1.68 1.27 7.73 8.22 9.35 10.23 8.06 9.51 * 7.62 8.54 8.59 10.18* 10.53* 10.99* 10.69* 8.65 9.72* 9.15* 8.00 10.39* 9.31* 0.37 0.72 0.44 0.67 0.50 0.96 0.95 0.41 1.08 0.46 1.20 0.70 0.55 0.64 0.78 0.38 0.60 1.00 0.30 a 10 21.5 46.4 80.0 b a 0.5 29 10 8 7 4 9 6 3.4 1.8 1.4 3.8 52.1 0.0 3.0 2.48 2.40 2.54 2.20 2.30 2.44 2.41 0.25 0.38 0.20 0.42 0.20 0.05 0.17 65.56 61.13 63.83 43.21* 27.25 69.70 57.96 11.56 11.44 9.19 19.80 25.17 13.15 10.12 5.17 5.23 5.04 5.29 5.95* 5.35 5.65 0.36 0.39 0.25 0.48 0.31 0.39 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. TERATOLOGY STUDIES WITH 2 ,4 ,5-T AND TETRACHLORODIOXIN 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 DMSO l-'xpt. 3 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 Dose d Average No i>r y„ ictui lillcrs morliilily/liller A verage letal weight J Ni « « *1 I 'll r I r.M .M l -NMl K iiim > \M .M A I IIS IN * ,- |„ V | A tN . I I ' I l ' I J I >- I 141 A I I I I M t« I Cicli p a ln lc s Species Compound * Key lo tellers: :i Kp

40; c Av. No. clef! palates in alTecIed lillers No. live lillers 10 9 6 dimclhyl sulfoxide; d K idney unom alics No. fillers aHeeled 1 0 1.2 2.6 0 0 0 0 0 0 0 8 2 0 7 0 2 3 1 1 0 4 T C P D expressed as /jg/kg; 2,4,5-T expressed us mg/kg. 1.0 1.7 4.6 6.5 2.0 2.4 4.2 4.-1 5.31.0 1.0 1.8 1.0 0 8.0 0 1.0 1.3 2.0 4.0 0 1.8 TERATOLOGY STUDIES WITH 2 ,4 ,5-T AND TETRa CHLORODIOXIN Mouse CD-I, random bred IZxpt. 1 DMSOc 2,4,5-T/Iech 2,4,5-T/Iech 2,4,5-T/lech l-Jxpl. 2 DMSO 2,4,5-T/unal TCDD TCDD Ivpl. 3 DMSO 2,4,5-T/lecli 2,4,5-T/anal 2,4,5-T/unal 2,4,5-T/anal I TCDD DHA/2J. inbred DMSO 2,4,5-T/Iech TCDD C57HI/6J, inbred DMSO 2,4,5-T/lech TCDD 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 DMSO TCDD Dose d ANI I | ( A I \ H 402 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 C arstens, L. A. (1967). Light and electron microscopic ob: Macaca mulatto monkey fed toxic fat. Amer. J. Vet. Res. 28, 1513-1526. A udus , L. J. (1964). The Physiology and Biochemistry of Herbicides. Academic York. B aker , 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 L IE V nD P .K . M ICH AKL W A T .'i 'N im . W \V HENSON Environmental Protection Acencw Idaho State D> hartnu nt >>l Environmental and ( otnmuntlv .'■¡vices. Boise. Idan■■Sj7-’&' 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 l s o 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 >umk* ««:s»n 1\•;:• *I'r-n - I Ici-.h* •r.* i r m.i. ‘ - o U ; 1■> :!i* I’ . *i* i. •*i I*• i»r;*v.i..i I \ . ' h ' ***•••m • fV z?/ '• i 1 if'* 9 336 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 en vironmental 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. TABI.K 1 I'ESTICIOF.S MOST COMMONLY l ORDER OF FRfcÇCEM Y (ilullp .- I / "Ucticidr-r.x f>"si d j ( n a im / '. r . •' 'll' ( l.ih vl parathimi ( >l’ j Trichlornfoii C I’H <>P »>kh: proceduic was to increase meu: facilitate the tek htliijUe. The -.it mitotic divi-|oii hi order to ;u;: 2443/HD 9 - /0 4 PE5TTCIDES AND CHROMOSOMAL ABERRATIONS 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. 337 TABLE 1 T ; 1 1 i Z i . | 1 I l •- I’ESTICIDES most commonly creo bv exposed slbjf . ctr in this st ud y * (listed in decreasing (■RL'ER OF FRRgi’ENCYl ,a ur A 1t.i‘. -.:iCldr-C\-pnX( (i (. ‘Himmi natnc I »«melon 1 thv! parathion Trichlorofon Naied Malathion I MCOIoi Piazinon Endosulfan PNOC Methvl parathion 1 uxaobene panethoate PPT 1 hlordimeform (iNvdemctonmethvI TEPP larbarvl Group t Hrrbicidt -r.»p-jsra 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 . oréame 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 M o o r h e a 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- - ' ii n .- r - having exclusive i.r, u. r.r:. However, becau?e „f technique proved to be .e exposed participant? :hrd to crops during 1972 trucáis 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 malignanh ?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- k 2444 J. YODER ct al. PESTICIDES AND CHROMOSOMAL ABERR. 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 v liromosomai 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. crease of nearlv 4 times the mean mini season. Mean break' per iXT-m |.,r ,, period (Table 111. A l s o notcw>rti.v 1- ; breaks, rcspcctivelv. during the big:. .. exposed eroup. On tile otiicr hand, :■ noted in Group B workers during b • bility of induced compensatory pr. :■ lianced chromosomal repair. 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 -■: in our exposed group approaches . .1; •any of these configurations, but uni ■ were sampled in the control er.u; 1 1 version in the A 2 chromosome Tinpear 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. 33 8 1 { 1 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- | j T \ 1: i . l . !I <*.t .TRFEN-: £ ' >F «. HK'tM \ t :;» LI.« 1«• NS A .ini ht; T ‘-r T ota l exposed 4- (Iroup A 11 nsectJCiJc-expo^ccl: G roup B ¡Herbicide-expose d l .W.i/ •Si d.‘.UI O 09 = 0 : 4 16 1O 26 — : tiki M id • «• j - 114 — 0 1 7 O-5 0 3 1 — 0.12 0—I 0. r 7 — o.oS 0-2 0 4 4 —0 22 0-3 I . 71 —0.24 0-6 Mean — S.E. 1.00 — 0.22 0-2 Ranee 0 75 = 0.27 0-3 0 31 = 0.18 0-2 1.50 - 0 :g 0-3 Mean — S.E. 0.*S — 0.10 O—1 Ranee 1.1$ 0-5 0 . 0 ; — 0.0s 0 —1 0-6 A Mean = S.E. 0.63 — 0 22 Ranee Mean — s.E 0.62 — 0 11 Ranee 0-2 1‘ 0 10 Chnmmf.il II O »j ( )ff ->CU Control- ,. i } r 1 ¿5 Chrowat.ti %4 .-f w . . \ \ l v ak : \ t :.' ' i i •'ll f* 1 Si = ° 35 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.- j 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.rsT K JY s .1 ' . ; . s M s 1.1 '• •. ‘ - M 11 . c .im linU c.. M..— . i " ‘ : : ^ l-.v.ws H J Ic mHil.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.ile > ■■ ..1 i s l.Li. HiRiK. Mu'.ii:' ■::i i .v . - u:.: ' ■l'|-4 I■( I-', 2445 J- v o d e r - ’’d e s w e r e s t a i n e d wjt|, s m r e r to av o id h i ^ .in e d m icroscopic 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 e d w h e n e v e r there ap. e n t . T h e c r i t e r i a 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 er i j ’ 'h ro m a iid breaks fi- sea son M id - O 3! = 0.1 2 i 3 3 (l 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. i | , l 0-3 05 PESTICIDES AND CHROMOSOMAL ABERRATIONS ri al = 0 33 o-<» j REFERENCES 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 um an peripheral leukocyte system. M ut a tu m h'is . s iooqi 4 B erg . G. L lEd.l. F a r m Chttm ca is Handbook Meister W illoughbv. Ohio. 1073 3 E p s t e i n . S. S.. Control of chemical pollutants S a t u r e . 4 4 ' .10701 m o - m o 4 E p s t e i n , s . 5 .. a n d M. S. L eg a to r , in The M n;j<;em:it \ a y Pe sti cid es. C - m o ftt> ami h i .Tmate-n. M.I.T., C a m bridc c. Mass.. 1071. p. 47. 3 E v a ns , H. J.. P opula tion cvtogcnetics a nd environm ental factors, in P. A J acobs . \V. H P rice a n d IV L a w (Eds ¡. H u m a n P-epulatian L vt.-a 11, ’ ,cs. W illiams a n d Wilkin- P.dliiiion. io"o pp 100-404. o F rea k . I > K H . I',sti c: d i Ji:,ie\ 4th cd.. College Science Publishers. S t a le College. Pa . 101.0 7 Ci Erh ak d t . K.. T he t r e a tm e n t of hu m an chromosome* . >1 ; i//a. results in I’ VuCKL .and c, K-.KRliORN lE d s .. (.hem¡cat M nta c. 10 os :n Mamma:.- ami M a n . Springer. New York 10-0 1 r i >i breaks observed per i gaps found in anv single -eason cultures to 5 in the 1 volunteer rose from 2 to in each of the four cases \hihited a reduction the high exposure pi riot], 'unn. dimples. Member< ■IriUI■B -hoUtd IV- ' - 1 . - n iR D T K '■ ¡.<"4 I 4( ! 44 M i n a g e m t a l - i i i i ; . r-u c'm ir.e e " an ii.e:.-■ hlicheii /.i i i k u l u i r e : ; > ■ i 1 • ■I Muta tion Research. 21 (1073; 341-14 r KIscvicr Scientific Publishing Corr SH O R T COM M UNICATI y H o o p i n g a RNER. R.. a s h A. \V B l o o m e r . Lvm p h ocyu- chromosome analvsi* of pv>ti Chinese hamster bone marrow ■ N-OH-CHA failed to induce an larlv negative in a liost-mediat implantation loss in rats1-' ait: 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 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. 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. C ■u larval feeding. Although the n Alii>r>-\ i.m.iiviiirlh vl-A lll\ cvci.-lu. - \ ■ li'.irii-.V-iinri.— i2-.:.i. ■ 2447 4 -//J ^ ? 3 / cp? î 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

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 spectru»i 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.i»J 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 f n m o tu M i irw u p i 2 ,4 -D ( O M M U I I I M , A-t A-2 * 3 It C L> £ 2 5 0 .0 0 0 .1 l 1 « 21 2 JO.OOO 3 3 b 19 2 .0 0 0 & 8 l ■j H IS 2 l 0 .2 0 0 4 5 2 .1 0 .0 2 0 0 l l 4 0 .0 0 2 - 0 0 ■ T u u l IllbM T V td num ber n( h rtM lI 1: IH 7 7 r. ■' 1 9 G J-r to ta l .■ 41 l 1 41 1 « « **2 F 1 1 0 .1 - ' h i , 19 1 5 ,1 3 X ' o.c, 0 .5 3 | chro: ug. This Ijypothesis iriehloroa thlorine a irtected 1 of2,«-D ejtogenesi Tirlous er. (1 2 J .G 4 2 . 5( 10 bet** : - 1 IPM | 1 ! A n t i c i p a i « ! «urn* b ir o f b rttk i (o n b u n o f ch ro m o ­ som e i n | i b | ¿0 0 1 Fig. .1 .0 9 71. j 1 8 .7 b 0 .2 2 | :i.2 i | lb.07 K .4 f i l (> .0 4 I 18 8 0 .2 1 0 .2 0 1 0 . id | 1 0 .il 1 N o ««. ■ 10. i l . I d e c r m o f f r r * « l« M n . P > 005 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 mg/kg (LDcn/ 6 ), and 10 r.g/kg (LD^n/30). The data obtalni 50 50 50 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. 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 Cone (In lymph from unpe •«asltive 1« s ig n th ;Iteard. KFERENCE e In the number of; 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 o n , s y m m e tr ic t h i s 2 , it -D o n o r m a llty spectru*ed a c e n t r i c f ra g m .,,^ e v »? v<- ¿i 5v. rPv r x )> r l b u t e d random ly 0r » tily d i s t r i b u t e d oytr irm s. The maximum •id s h o r t arm s (70.5 * 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 . 3 è Fig. 2. Multiple aberrations, 2.H-D, In vivo, 300 mg/kg, magnification of 10 * 90 . 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,^,5••lehloroacetlc 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. T able 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 . * £ a 6 2 © ;s of 300 mg/leg The data obtain ns .n Table 3» wh ig/kg, which .ency Identical. .ly from the : m g / k g , which increase in ' a b n o rm a lltle § \ E e - *s 5 e 2 1 re a u e n c r a t a h e tr t m m e ta p h ases. % e h fsM n v t « ti c e lts w ith m u ltip le tU m iw in in tfte m tw iM ì f ih frr ilM in i t ZJ G S • iO n * m # % * « © z 1! 10 6 1200 0 J .1 3 i0 .l6 5 0 0 * T r p e s o f •nerraiMM»« p e t 1 OO c r lta c * ï l ï C ! * ? i t i il 4 0 .2 5 0 : 5 ae • 2 £ C 3 e E I II C ■ ~ 2 0 .0 0 3 3 1 .0 0 0 .0 8 3 0 no 6 1200 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 1 00 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 V » 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 C«w>* tra i 10 1000 o .n o ± o ^ 6 4 0 0 7 0 .0 0 7 0 1 .0 0 0.700 0 0 ■arance of cell ..tea among the ; of damaging Tect develope eparatlon, s o • atIon Induced ( hat did and s action of 2, the importane' 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 J. J. Unrau, Can. Seed Growers Assoc. 1952-1953 Ann. Report., pp. 25-28, 1953Unrau, 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* 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 19717. 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 Urt : rJ • 10 2 4 5 $ '/// O-^ ,6P V 2454 Vol. 115, No. 5 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 Printed, in V S A . LEUKEM IA AND FARM PRACTICES IN IOWA' THIS MATERIAL MAY BE PROTECTED BY COPYRIGHT LAW TITLE 17 li.S . COOE NOTICE L E O N F . B U R M E IS T E R , S T E P H A N IE F . V A N H E R a n d P E T E R IS A C S O N Burmeister, L F. (Dept, of Preventive Medicine and Environmental Health, University of Iowa, Iowa City, iA 52242), S. F. Van Lier and P. isa cso 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 stu d ies have been based on a w ide ran ge o f 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 o f the importance of farm ing in these states and because of the identifica­ tion o f h igh -rate leu k e m ia m ortality counties in this area (6). More recent studies (7) have continued to indicate that leukem ia mortality rates are elevated in the midwestern states. A l­ though m ortality from all cancers was R e ce iv e d for p u b lic a tio n A u g u s t 3 1 , 1981, a n d in fin a l fo rm N o v e m b e r 3, 1981. 1 F ro m t h e D ep t, o f P r e v e n tiv e M e d icin e a n d E n ­ v ir o n m e n ta l H e a lth , U n iv e r s ity o f Iow a, Io w a C ity , IA 52242. ( R e p r in t r e q u e s ts to D r. B u rm e is te r.) T h is w o rk w a s s u p p o rte d by P u b lic H e a lth S e rv ice g r a n t 1 R 0 1 -C A 2 4 3 0 2 -0 1 -E D C fro m th e N a tio n a l C a n c e r I n s titu te . 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 pro720 2455 . 0 - ^ 721 LEUKEMIA IN IOWA FARMERS 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 farm ing practices are associated with leukem ia m ortality rates. M aterials 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 S even th (code 204) and E ighth (codes 2 0 4 -2 0 7 ) Revisions of the International Classifica­ tion o f D is e a s e s (ICD) (21, 22), w ere 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 co n tr o ls w ere m atch ed 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 1 9 7 1 -1 9 7 8 . The entire Nebraska study was based on occupations defined by the B ureau o f the C ensus. 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 th e death certificate analyses. However, agricultural produc­ tion in Iowa counties has changed very lit t le d u rin g th e p ast th ree d ecad es. Spearm an 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 d istrib u tion s o f 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 low est producing 66 counties ranged from 1.52 for acres in oats to 3.49 for acres in soybeans. Estim ated relative risks and associated confidence intervals were computed as suggested by M iettinen (26). All computa­ tions utilize the m atching of two controls to each case. R esults H eart 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 ig u re 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 Iow a c o u n tie s for s e le c te d a g ric u ltu ra l pro­ d u c tio n c h a r a c te ris tic s . A , m ilk cow s; B, c o m ; C, so y b e a n s; D , h e rb ic id e s ; E , e g g -la y in g ch ick en s. per cent in N ebraska). Cancer d eaths other than leukem ia 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 sim ilar are the elevated risks of leukem ia m ortality for farmers. A n odds ratio of 1.25 (95 per cent confidence lim its o f 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 723 LEUKEMIA IN IOWA FARMERS 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 Cases Iowa Occupational group Controls No. % N ebraska % No. T e a c h e rs E n g in e e rs , s c ie n tis ts F a n n e rs C le rk s , s a le s p e rs o n s C a r p e n te r s , w o o d w o rk ers P r in te r s M a c h in is ts , m e c h a n ic s L a b o re rs N o o c c u p a tio n lis te d O th e r 17 49 661 116 89 12 71 116 5 539 1.0 2.9 39 .5 6.9 5.3 0.7 4.2 6.9 0.3 32 .2 9 25 43 3 84 31 3 33 49 65 35 2 T o ta l 1675 1084 0 .8 2.3 3 9 .9 7.7 2.9 0.3 3.0 4.5 6.0 32.5 Iowa N ebraska No. % No. % 37 64 1184 23 0 183 8 162 29 8 19 1165 1.1 1.9 35 .3 6.9 5.5 0.2 4.8 8.9 0.6 34 .8 12 66 781 163 52 9 77 126 161 721 0.6 3.0 3 6 .0 7.5 2.4 0.4 3.6 5.8 7.4 3 3 .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 Cases No. of farmers % Farmers Year of birth 1869-1889 1890-1900 1901-1947 Year of death 1964-1970 1971-1978 Age (years) at death <65 *66 Controls No. of farmers % Farmen Odds ratio 95% CL* 166 290 205 49.7 47.2 28.2 392 488 304 52.0 39.9 22.2 0.89 1.36 1.39 0.67-1.18 1.10-1.68 1.11-1.73 344 317 40.4 38.5 640 544 37.6 33.0 1.15 1.36 0.96-1.39 1.11-1.66 116 545 24.1 45.7 166 1018 18.5 41.5 1.36 1.21 1.02-1.80 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 ra tio for y ea r s o f d eath in 1 971-1978 was elevated in Iowa; how­ ever, the odds ratio for the years of death 1957-1965 was markedly higher in N e­ braska. As noted in table 2, the greatest risk for leukemia mortality in Iowa farmers ap­ pears to be in th ose 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 in crea sed le u k e m ia m o r ta lity risk s among farmers for those born from 1890 to 1900. However, neither association is sta tistic a lly sig n ifica n t for those born after 1900. The relatively low livestock producing counties have increased odds V 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, 19 6 4 -1 9 7 8 Production categories by counties S o y b e n n s/a c re 3 3 h ig h e s t O th e r s C o rn /a c re 33 h ig h e s t O th e r s M ilk p ro d u c ts so ld 33 h ig h e s t O th e r s C a ttle 33 h ig h e s t O th e r s H ogs 3 3 h ig h e s t O th e r s M ilk cow s 33 h ig h e s t O th e r s E g g -la y in g c h ic k e n s 33 h ig h e s t O th e r s F e r tiliz e r 3 3 h ig h e s t O th e r s In s e c tic id e s 3 3 h ig h e s t O th e r s H e rb ic id e s 3 3 h ig h e s t O th e r s K> OT CO VT\ 6s * CL, confidence limita. Year of b irth (of case) Before 1890 1890- 1900 A lter 1900 Odds ratio 95 * CL* Odds ratio 95% CL Odds ratio 96% CL 0 .6 7 2 1.032 0 .4 1 5 - 1 .0 8 8 0 .7 2 7 - 1 .4 6 5 1.594 1.233 1 .1 2 9 -2 .2 5 0 0 .9 4 0 - 1 .6 1 6 1.405 1.376 0 .9 7 9 - 2 .0 1 6 1 .0 3 8 -1 .8 2 4 0.831 0 .9 4 7 0 .5 5 4 - 1 .2 4 7 0 .6 3 8 - 1 .4 0 6 1.634 1.201 1 .1 6 8 -2 .2 8 5 0 .9 1 2 - 1 .5 8 2 1.384 1.389 0 . 9 8 0 - 1 .9 5 4 1 .0 3 9 -1 .8 6 7 0 .9 0 6 0 .8 7 7 0 .5 8 6 - 1 .4 0 1 0 .6 0 5 - 1 .2 7 1 1.187 1.474 0 .8 3 5 - 1 .6 8 5 1 .1 2 6 -1 .9 2 9 1.302 1.454 0 . 9 2 6 - 1 .8 2 9 1 .0 8 4 - 1 .9 5 0 0 .9 6 9 0.831 0 .6 3 2 - 1 .4 8 5 0 .5 7 0 - 1 .2 1 3 1.287 1.414 0 .9 2 1 - 1 .7 9 8 1 .0 7 2 -1 .8 6 4 1.231 1.522 0 . 8 7 9 - 1 .7 2 2 1 .1 3 1 - 2 .0 4 9 0 782 0 .9 8 7 0 .5 1 2 - 1 .1 9 3 0 .6 7 5 - 1 .4 4 6 1.246 1.429 0 .8 7 3 - 1 .7 7 8 1 .0 9 5 -1 .8 6 5 1.400 1 .376 0 .9 5 4 0.841 0 .6 2 3 - 1 .4 6 1 0 .5 7 6 - 1 .2 2 8 1.171 1.490 0 .8 2 7 - 1 .6 5 8 1 .1 3 6 -1 .9 5 3 1.446 1.345 1 .0 2 7 - 2 .0 3 6 1 .0 0 4 - 1 .8 0 2 1.105 0 .7 9 2 0 .6 8 3 - 1 .7 8 8 0 .5 5 7 - 1 .1 2 5 0 .9 5 4 1.627 0 .6 5 9 - 1 .3 8 0 1 .2 5 0 -2 .1 1 8 1.532 1.314 1 .0 5 3 - 2 .2 2 9 0 .9 9 7 - 1 .7 3 2 1.260 0 .7 3 0 0 .7 8 6 - 2 .0 1 8 0 .5 1 2 - 1 .0 4 2 1.089 1.548 0 .7 6 7 - 1 .5 4 8 1 .1 8 3 -2 .0 2 6 1.340 1.414 0 . 9 2 9 - 1 .9 3 4 1 .0 7 0 - 1 .8 7 0 0.731 0 .9 5 4 0 .4 2 0 - 1 .2 7 1 0 .6 8 6 - 1 .3 2 7 1.323 1.381 0 .9 2 2 - 1 .9 0 0 1 .0 6 1 -1 .7 9 7 1.129 1.626 0 . 7 6 2 - 1 .8 7 3 1 .1 6 6 - 1 .9 9 8 0 .7 6 7 0.951 0 .4 6 2 - 1 .2 7 3 0 . 6 7 6 - 1.337 1.104 1.528 0 .7 7 3 - 1 .6 7 5 1 .1 7 1 -1 .9 9 4 1.595 1.278 1 .1 0 5 -2 .3 0 1 0 .9 6 6 - 1 .6 9 1 . 1 .0 0 8 - 1 .9 4 9 1 .0 1 9 - 1 .8 5 7 725 LEUKEMIA IN IOWA FARMERS ratios. None of the agricultural production figures evaluated in Nebraska led to increased risk am on g farm ers in th e 1890—1900 cohort. It is for those born after 1900 that the Iowa and N eb rask a stu d ie s h ave th e 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 h igh est number of acres treated with insecticides. None of these farming practices were associated w ith leukem ia mortality in Iowa. Only acres treated w ith herbicides and egg-layin g chickens per county were sta tistic a lly significant at the 5 per cent level. The odds ratios for Iowa farmers for specific leukem ia cell types are summarized in tab le 4. O nly those d yin g 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 a cu te m y elo id le u k e m ia s. B oth chronic lym phatic and unspecified lymphatic leukem ias cause increased mortality in Iowa farmers. The odds ratios for chronic lymphatic leukem ia are elevated in th ose born a fter 1890 (tab le 5). A lth ou gh th e odds ra tio s for u n sp ecified lym phatic leu kem ia are greater th an 1 for each birth cohort, none is statistically significant, due in part to sm all numbers in each cohort. Odds ratios for chronic and unspecified leu kem ias according to county agricultural production Figures associated with combined leukem ia types are summarized in table 6. Chronic lymphatic leukem ia 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 w ith soybeans per acre and acres treated w ith herbicides. Unspecified lymphatic leukem ia mortality in farmers is associated w ith com per T able 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 Cases ICD No. Controls % No. of farm ers % Farm ers No. of farm ers Farm ers Odds ratio 95% CL* A c u te ly m p h a tic 2 04.0 28 28.9 69 3 5 .6 0 .6 8 0 . 3 7 - 1 .2 3 C h ro n ic ly m p h a tic 204.1 132 4 5 .8 207 35 .9 1.70 1 .2 2 - 2 .3 8 U n s p ec ifie d ly m p h a tic 2 0 4 .9 64 5 1 .2 102 4 0 .8 1.66 1 .0 3 - 2 .6 8 A c u te m y elo id 2 0 5 .0 86 3 0 .7 168 3 0 .0 1.04 0 .7 4 - 1 .4 8 C h ro n ic m y elo id 205.1 46 32 .6 90 31 .9 1.04 0 .6 5 - 1 .6 5 U n s p ec ifie d m y elo id 2 0 5 .9 36 3 6 .7 80 40 .8 0 .8 0 0 .4 5 - 1 .4 1 2 0 6 .0 10 32 .3 19 30.1 1.07 0 .4 4 - 2 .5 9 207.9 31 41 .3 60 4 0 .0 1.07 0 .5 8 - 1 .9 7 — C h ro n ic m y elo id L e u k e m ia u n sp e c ifie d * CL, c o n fid e n ce lim its . 726 BURMEIOTER, VAN LIER AND ISACSON T able 5 Odds ratios (ORs) for leukemia mortality in white, male Iowa farmers over 30 years of age for selected leukemia types and year o f birth, 1 9 6 8-1978 Year of birth type C h ro n ic ly m p h a tic U n s p ec ifie d ly m p h a tic ICD No. 1890-1900 Before 1890 After 1900 OR 9 5 * CL* OR 95* CL OR 95* CL 204.1 1.00 0 .5 4 - 1 .8 5 2 .0 3 1 .2 4 - 3 .1 0 1.80 1 .0 9 -2 .9 7 204.9 1.58 0 .6 5 - 4 .5 4 2.30 0 .9 7 - 6 .9 7 1.25 0 .6 4 -2 .5 5 * C L , c o n fid en ce lim its . T able 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 Highest 33 counties County characteristics O ther counties OR 95* CL* OR 95* CL S o y b e a n s/a c re C h r o n ic . ly m p h a tic U n s p e c ifie d ly m p h a tic 2 .2 1 0 .6 2 1 .3 3 - 3.6 6 0 . 2 5 - 1.52 1.39 2 .4 9 0 .9 7 -2 .0 0 1 .3 8 -4 .4 8 C o rn /a c re C h ro n ic ly m p h a tic U n s p e c ifie d ly m p h a tic 1.34 4 .6 3 0 . 8 7 - 2.0 6 1 .8 2 -1 1 .7 4 1.94 1.00 1 .2 9 -2 .9 2 . 0 .5 6 -1 .8 0 M ilk cow s C h ro n ic ly m p h a tic U n s p e c ifie d ly m p h a tic 1.19 4 .9 4 0 . 7 6 - 1.85 1 .9 6 -1 2 .4 7 2 .1 0 0 .9 4 1 .4 1 -3 .1 4 0 .5 2 -1 .7 0 E g g -la y in g c h ic k e n s C h ro n ic ly m p h a tic U n s p e c ifie d ly m p h a tic 1.36 2 .4 7 0 . 8 2 - 2.25 1 .0 3 - 5.92 1.80 1.37 1 .2 5 -2 .5 9 0 .7 7 -2 .4 5 H e rb ic id e s C h ro n ic ly m p h a tic U n s p e c ifie d ly m p h a tic 1.89 1.21 1 .1 6 - 3.0 8 0 . 5 1 - 2.85 1.5 0 1.90 1 .0 3 -2 .1 8 1 .0 7 -3 .3 7 . * C L , c o n fid en ce lim ite . acre, number of m ilk 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 stom ach, prostate and lip cancer, as well as lymphomas and m ultiple myeloma. However, leukem ia 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 dem onstrate th at such an as­ sociation exists, but to diligen tly search for reasons for the association. T he N eb ra sk a stu d y o f B la ir 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 sta te s ind icates th a t m odern farming •26 727 LEUKEMIA IN IOWA FARMERS practices used in corn production may be a cause of the higher leukem ia m ortality 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 num ber of acres treated w ith in secticid es in N e­ braska are associated w ith leukem ia mor­ tality in farmers born after 1900. These results also tend to im p licate modern farming practices as possible causes of leukemia. There is no evidence linking leukemia m ortality 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 a sso cia ted w ith increased leukemia m ortality 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 ind icate th at a sta tis­ tically significant association existed be­ tween farming and leukem ia mortality, and that the greatest excess of leukem ia mortality was in poultry farmers. Analyses by type of leukem ia indicate that chronic and unspecified lymphatic leukemias cause increased m ortalities in Iowa farmers. Thus, it appears that it is the ly m p h atic le u k e m ia s th a t are of greatest concern. Sixty-three per cent of incident acute lym phatic leu kem ias in Iowa males in 1 9 6 9 -1 9 7 9 occurred in in­ d iv id u a ls und er a g e 30 y e a r s. C on­ 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 lym phatic leukem ia with number of dairy cows and corn production per acre by county. Donham et al. (14) showed significant association between acute lymphatic leu kem ia incidence in Iowa and dairy farming. As noted above, acute lym p hatic leu k em ia m o rta lities were o f lim ited num ber in th is 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 so cia te d w ith u n sp ec ifie d ly m p h a tic leukem ia m ortality, any elem ents com­ mon to both com and dairy production are worthy of further investigation. M any agricu ltu ral in n ovation s th at 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 am ount of nitrogenous fertilizer applied has added to the agricu ltu ral ru n o ff problem (28). T h is problem is exacerbated by the fact that the nitroge­ nous w aste o f dairy a n im a ls is m uch greater than that of other common farm livestock (28). Although highly specula­ tive, one m echanism of increasing the risks for farmers for leukemia and other cancers is contam ination of shallow farm w ells and farm ponds. This research, of course, offers no direct evidence that sh al­ 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 p t to id en tify farm ing practices and specific m echa­ nism s that m ust be closely studied if the can cer risk s of farm ers are to be d e­ creased. R e fe r e n c e s 1. G u r a ln ic k L. M o r ta lity by o c c u p a tio n a n d c a u s e o f d e a th . V ita l S t a ti s t i c s S p e c ia l R e p o rt 1963:53(3). 2. M ilh a m S . O c c u p a tio n a l m o r ta l it y in W a s h ­ in g to n s t a te , 1950-71. Vol. 1-3. D H E W 5 5 2464 .3l5 (¿A r T c 137 icology Letters. 29 (1985) 13 7 -1 4 4 g K v te r F ra ss e u o , I he synthesis of \b u s e , 3 (1982]j \ TOXLetl. 1508 DNA AND PROTEIN SYNTHESIS INHIBITION IN CHINESE HAMSTER OVARY CELLS BY DICHLOROPHENOXYACETIC ACID h o la te secretor »83) 86A. i •'-> f hep atic Na, K.ced c h o le sta s is^ (Dichlorophenoxyacetic acid; cell cycle; DNA synthesis; protein synthesis) • (1984) UO-isi'J'' tran ssu lfu raiio VIV IANA A . R IV A R O L A . JO R G E R . B E R G E S S E an d H É C T O R F . B A L E G N O * :m „ 259 (1984^' P- B ain. R.k. p a th w ay in cir- Departamento de Biología Molecular, Universidad Nacional de Rio Cuarto. 5800 - Rio Cuarto. Córdoba (Argentina) r. (Received S ep tem b er 9 th . 1985) * (Accepted O c to b er 10th. 1985) * • an d irreversible- ■ th y l-P G E t p . H ep ato lo g y , gN SU M M A RY d R. Tritapepe?-* at 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 i bile it?i investigated in Chinese h a m ste r o v ary cells (C H O ) em ploying tw o d iffe re n t m eth o d s. T h e results show ed that th e h e rb id d e a ffe c ts D N A a n d p ro tein synthesis dep en d in g o n th e stage o f g ro w th an d m eth o d of ie. R elationshi 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 nvesi. (Suppl. by th e chem ical d e te rm in a tio n o f D N A and 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 w as re d u ce d m ark e d ly w hen cells tre a te d w ith 2,4-D w ere in confluency lls, P h arm aco lJ for 4 days a fte r reach in g p late au g ro w th . i S-adenosyi-i-'jJ E u r. J . D rugion in therapy, IN T R O D U C T IO N aphthylisothio- 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 stradiol-ireated and L . Okoiic.SA M e) in rats. t t *To w h om c o rre sp o n d e n c e sh o u ld be a d d ressed A b b rev iatio n s: C H O . Chinese h a m s te r o v ary cells: 2 ,4 -D , dich lo ro p h en o x y acetic acid ; 2 .4 .5-T. tn ch lo ro p h en o x y a c etic 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 RESUL 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 Fig. flasks with a 25-cmJ surface were used for the experiments. Trypsin (1:250 Difc (HU) 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 37°C. 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 2466 139 il defects. ¿ 2 /mphocytes^ ricity. 2,4-D^ >ther relatq (3H]uridixj5 corporation! growth [4], of 2,4-D i synthesis o f gentle shaking immediately after which 3 ml medium containing 15 Vo 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 ch an g ed fo r fresh m edium w ith o r w ith o u t I m M 2 ,4 -D . T h e D N A -specific radioactivity » a s d eter­ m ined. a . W ith 2.4-D ; • , w ith o u t 2.4-D . 2467 <0 -3.5(0 "l Fig. 3. C ells grow ing in n o rm al c u ltu re m edium were kept fo r 4 a d d itio n a l days at 37°C a fte r reaching, p la te a u g rp w th -T h e 'm e d iu m w as th e n c h an g e d fo r fresh m ed iu m w ith o r w ith o u t 2,4-D a n d th e 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. C ells were in cu b ated fo r 4 d ay s a fte r reaching p late au grow th. T h e m ed iu m w as ch an g e d for a n o th e r w ith o r w ith o u t I m M 2 .4 -0 . an d a 10-m in pulse w as given w ith I p C i/m l o f []H ]th y m id in c every 2 h . A u to ra d io g ra p h y was c arried o u t im m ed iately . P e rcen tag e o f labelled cells 12 h a f te r ch an g in g the c u ltu re m edium : o p en bars, c o n tro l; so lid b a rs, cells w ith 2.4-D . ^ <7P-/'=Zj> 2469 142 r& Fig. 5. P rotein-specific rad io activity o f ceils trea te d as in d icated 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} Fig. 6. 2 ,4 -D to a final co n cen tratio n o f I m M , was a d d e d to a cell cu ltu re in logarith m ic grow th an d DNA synthesis follow ed fo r 24 h. In o th er series o f flasks th e m edium w ith 2.4-D w as rem oved after 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 to j 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 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 w ith n o rm al m edium . 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. ACK NOW LED GEM EN TS 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 Científicas y Téc­ nicas (Argentina). REFEREN CES 1 R . D u ffa rd . G .M de M oro a n d A .M .E . D u ffa rd . H a tch in g a n d lipid c o m p o sitio n o f chick brain from eggs tre a te d w ith 2 ,4 -D ich lorophenoxyacetic bu ty l ester. T o x ico lo g y , 24 (1982) 305. 2 C . K o rte a n d S .M . Ja la l, 2.4-D induced clasto g en icity a n d elevated ra te s o f sister ch ro m a tid ex­ ch an g es in cu llcred hu m an lym phocytes. H e red ity . 73 (1982) 224. 2471 Toxicology L Hscvier 3 R. N ahU A l-N a jja r a n d A .S . S o lim an. C ytological e ffe c u o f h erbicides, i. E ffects o f 2,4-Dfc 2,4,5-T on m eiotic cells o f w heat a n d tw o related species. C y to lo g y , 47 (19S2) 33. TOXLett. 15 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 . H am a n d W .L . M cK eehan. M edia a n d grow th req u irem en ts, in W .B . J a k o b y and I.H . P a s ta a ^ S (E d s.) M ethods in E nzym oiogy V ol. LV1II, A cadem ic P ress. N ew Y ork, 1979. 6 C . S h ip m an , J r ., T ry p sin , A: m am m alian tissues, in P .J . K ruse, J r . a n d M .K . P atterso n , AMITRO OF THE MICE T issue C u ltu re M e th o d s an d A p p licatio n s, A cadem ic P ress, New Y ork, 1973. 7 A .B . P a rd e e, A restrictio n point for c o n tro l o f n o rm al a n im al cell p ro life ra tio n , P ro c. N a t l . , Sci. U S A , 71 (1974) 1286. (NOD me 8 B. G retchen a n d R. Y am chesky, A u to ra d io g ra p h y , in W .B . J a k o b y a n d l.H . P a st a n (E ds.) M eth o d ^ in E nzym oiogy, V ol. LV1I1, A cadem ic P ress. New Y ork. 1979. ■ 9 R .L .P . A dam s, in C ell C u ltu re for B iochem ists. E ls e v ie r/N o rth -H o lla n d , A m ste rd am , 1980, p . ; 10 H .N . M u n ro a n d A . F leck, R ecent dev elo p m en t in th e m easu rem en t o f nucleic acids in biolog m aterial. A n aly st, 91 (1966) 78. SATORU N OHHARA. Aburahi Ll 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 ^ geearch U 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 (Received S (Accepted ( tio n to O N A re p lica tio n , J . Cell P h y sio l., 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 ch ro m o so m e s, J . Cell P h y sio l., 95 (1978) 333. SU M M A R ' Strain dii in N O D . 1C i m o n th s .. but n o t in c HOD s tra tr 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 O verall E v a lu a tio n s o f C arcin ogen icity: A n U p d a tin g o f I A R C M o n o g r a p h s V o lu m e s 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 Experimental Animals — IARC Monographs Volumes 1-17 (IARC intern, tech. Rep. No. 78/003), Lyon 3. IARC (1979) Criteria to Select Chemicals for 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) 2.4D 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. lá 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. 2.4D 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 2479 AA>) rp CHLOROPHENOXY HERBICIDES 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 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 ìd e o t a p e s n o w a v a il a e 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' --------------------------------------------- -1 YES! I want to continue to receive Environmental Health Monthly. CCHW is a non-profit tax-exempt organization that serves as an Environmental Crisis Center. Name__ 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. Address. We count on your support for Environmental Health Monthly. Annual Subscription Rates: O O O O S35 Health Professionals $15 Grassroots Community People Check Enclosed or Charge to my credit card: Visa/Mastercard 5 Expiration Date Signature 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, Managing Editor, EHM, P .0 .926 Arlington, VA 22216 (703) 276-7070. V____________________________ J Citizens Clearinghouse for Hazardous Wastes, Inc. P.O. Box 926 Arlington, VA 22216 (703) 276-7070 Environmental Health Monthly PRAY FOR PEACE _ 2485 8 p x# ^ S tUnited States Department of Agriculture Forest Service Pacific Northwest Region November 1988 Managing Competing f and Unwanted >■ Vegetation Final Environmental Impact Statement Appendices D & H 4-¿,o 8 I HlS.kASa( O M N I E n v iro n m e n ta l S erv ices 1987. P r e lim in a ry h e a lth e ffe c ts e v a lu a tio n fo r p o llu ta n ts g e n e r ­ a te d b y field b u r n in g , sla s h b u r n in g a n d r e s id e n tia l w o o d c o m u b u s tio n . M a y P r e p a re d fo r O r e g o n S ta te D e p a r tm e n t o f E n v iro n m e n ta l Q u a lity . I O r e g o n S ta te D e p a r tm e n t o f E n v iro n m e n ta l Q u a lity (O re g o n D E Q ) J u n e 1986. F ie ld a n d s la s h b u r n in g P M -1 0 /T S P m a x im u m Im p ac t s tu d y . O r e g o n S ta te D e p a r tm e n t o f E n v iro n m e n ta l Q u a lity (O re g o n D E Q ) F e b r u a ry 1987. O r e g o n to x ic a ir p o llu ta n t e m is s io n s In v e n to ry . h. O z k a y n a k , H ., a n d S p e n g le r, J.D. F e b ru a ry 1986. H e a lth e ffe c ts o f a ir b o r n e p a rtic le s. E n e rg y a n d E n v iro n m e n ta l P o licy C e n te r, J o h n F. K e n n e d y S ch o o l o f G o v e r n ­ m e n t, H a r v a r d U n iv e rsity , C a m b rid g e . P e a rc e , N .E ., S m ith , A .H . e t al. 1986. N o n - H o d g k ln 's ly m p h o m a a n d e x p o s u r e to p h e n o x y h e rb id d e s , c h lo ro p h e n o ls , fe n c in g w o rk , a n d m e a t w o rk s e m p lo y ­ m e n t: a c a s e -c o n tro l s tu d y . Br. J. In d u s tr . M e d . 43:75-83. P e te r s o n , S. 1983. G r a z in g Im p a c ts o n b a c te ria l w a t e r q u a lity - A lsea r a n g e r d istric t. P r e p a re d fo r th e U .S.D .A . F o rest S erv ice, R e g io n VI. n- R a d ia n C o rp o ra tio n F e b ru a ry 1986. W a s h in g to n to x ic a ir c o n ta m in a n ts s tu d y - r e v is e d fin al re p o rt. P r e p a re d fo r W a s h in g to n S ta te D e p a r tm e n t 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 o rta lity o f 2,4 -D a c id a n d 2,4,5-T a cid h e rb ic id e a p 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. S o ft tis s u e s a rc o m a a n d e x p o s u re to p h e n o x y h c rb ic id e s a n 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 o rta lity S tu d y o f p e rs o n s e x p o s e d to d io x in in a tric h lo ro p h e n o l-p ro c e s s a c c id e n t th a t o c c u rre d in th e BASF A C o n N o ­ v e m b e r 17,1953. A m . J. In d . M e d . 3:179-89. H-W U.S. E n v iro n m e n ta l P ro te c tio n A g e n cy (U S E P A ) 1976. In te rim p r o c e d u r e s a n d g u id e lin e s fo r h e a lth risk s a n d e c o n o m ic im p a c t a s s e s s m e n ts o f s u s p e c te d c arc in o g e n s. E ed eral R e g is te r 41: 21402-21405. U.S. E n v iro n m e n ta l P ro te c tio n A g e n cy (U S E P A ) 1984. P r o p o s e d g u id e lin e s fo r c a rc in o g e n ris k a s s e s s m e n t; for e x p o s u r e a s s e s s m e n t; fo r m u ta g e n ic ity risk a s s e s s m e n t; fo r h e a lth a s s e s s m e n t o f s u s p e c t d e v e lo p m e n ta l to x ic a n ts. F e d e ra l R e g is te r 49L 46294-46301; 46304-46312; 46314-46321; a n d 4632446331 (N o v e m b e r 2 3 ,1 9 8 4 ). Z ack , J.A. a n d G a ffey , W .R. 1983. A m o r ta lity s t u d y o f w o rk e rs e m p lo y e d a t th e m o n s a n to c o m p a n y p la n t in N itro , W e s t V irg in ia . E n v iro n . Sci. R es. 26:575591. Z ack , J.A ., a n d S u s k in d , R.R. 1980. T h e m o rta lity e x p e rie n c e o f w o rk e rs e x p o s e d to te tra c h lo ro d ib e n z o d io x in in a tric h lo ro p h e n o l p ro c e s s a c c id e n t. JO M 22(1 ):1 1-14. U 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 HO to H I IUi IIUI lUillUM I lOUlitt Risk >y sment B ib lio g ra p h y -H e a lth R isk /E p id em io lo g y A m e s, B .N ., M a g a w , R., a n d G o ld , L S . 1987. R a n k in g p o ss ib le c a rc in o g e n ic h a z a rd s . S cience 236:271-280. A x e lso n , O . e t aL 1980. H e rb ic id e e x p o s u r e a n d t u m o r m o rta lity . S c a n d J. W o rk E n v iro n . H e a lth 6:73-79. C a la b re s e , E.J. 1983. S calin g : a n a tt e m p t to A nd a c o m m o n d e n o m in a to r . In: ■r “P rin c ip le s o f a n im a l e x tra p o la tio n ," e d . C a la b re s e , E.J., N e w Y o rk , J. W ile y 8c S o n s. p p . 499-527. C a lifo rn ia A ir R e so u rc e s B o a rd D e c e m b e r 1981. In f o r m a tio n r e la tin g to d e v e lo p m e n t o f a s ta te a m b ie n t a ir q u a lity s t a n d a r d fo r fin e o r in h a la b le p a rtic u la te s. C r u m p , K.S., a n d C o m p a n y , Inc. 1986. W o rs t c a s e a n a ly s is s t u d y o f fo re s t p la n ta tio n h e rb ic id e u se . M a y . P r e p a r e d f o r F o re s t L a n d M a n a g e m e n t D iv isio n , D e p a r t­ m e n t o f N a tu r a l R e so u rc es, S ta te o f W a s h in g to n . D a v id s o n , I.W ., P a rk e r, J.C ., a n d B ellies, R.P. 1986. B iological b a s is fo r e x tra p o la tio n a c ro s s m a m m a lia n s p e ­ cies. R e g u la to ry T oxicol. P h a rm a c o l. 6:211-237. D o s t, F.N . S e p te m b e r 17 ,1 9 8 6 . A n e s tim a te o f c a rc in o g e n ic ris k a sso c ia te d w ith p o ly a ro m a tic h y d ro c a rb o n s in s m o k e fro m p re s c rib e d b u r n i n g in fo re s try . S u b m itte d to B u re a u o f L an d M a n a g e m e n t, W a s h in g to n D .C . F ln g e rh u t, M .A . e t al. 1984. R e v ie w o f e x p o s u re a n d p a th o lo g y d a ta fo r s e v e n c a s e s r e p o r te d a s so ft tis s u e s a rc o m a a m o n g p e rs o n s o c c u p a tio n a lly e x p o s e d to d io x in -c o n ta m in a te d h e rb ic id e s. In: " P u b lic h e a lth ris k s o f th e d io x in s ," e d . L o w ran c e , W .W ., L os A lto s, C A , K a u fm a n n . p p . 187-203. H a rd e ll, L., a n d E rik s so n , M . 1981. S o ft tis s u e sa rc o m a s, p h e n o x y h e rb ic id e s a n d c h lo rin a te d p h e n o ls . L an c et (A u g u s t 1): 250. M-1M .H u m a n E p ic 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 a lig n a n t ly m p h o m a a n d e x p o s u r e to c h em ica ls, e sp e c ia lly o rg a n ic s o lv e n ts , c h lo ro p h e n o ls a n d p h e n o x y a cid s: 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 a se -c o n tro l s tu d y : s o ft-tis s u e sa rc o m a s a n d e x p o s u r e to p h e n o x y a c e tic a c id s o r c h lo ro p h e n o ls . Br. j. C a n c e r 39:711-17. H a rt, R .W ., a n d F ish b e in , L. 1985. In te rs p e c ie s e x tra p o la tio n o f d r u g a n d g e n e tic to x ic ity d a ta . In: "T o x ico lo g ic a l R isk A s se ssm e n t Voi. I," e d s. C la y s o 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 o a r, S.K ., e t al. 1986. A g ric u ltu ra l h e r b ic id e u s e a n d risk o f ly m p h o m a a n d so ft tis s u e sa rc o m a . JA M A 256(9): 1141-1147. H o n c h a r, P .A ., a n d H a lp e rin , W .E. 1981. 2,4,5-T, tric h lo ro p h e n o l a n d so ft tis s u e sa rc o m a . L an c et (J a n u a ry 31):268-9. L y n g e, E. 1985. A fo llo w -u p s t u d y o f c a n c e r in c id e n c e a m o n g w o rk e rs in m a n u f a c tu r e o f p h e n o x y h e rb ic id e s in D e n m a rk . Br. J. C a n c e r 52:259-70. M u r p h y , S.D. 1986. I n tr o d u c tio n a n d h isto ric a l p e rs p e c tiv e o f risk a s s e s s m e n t. W a s h in g to n P u b lic H e a lth 6(1):7-12. N a tio n a l R e se a rc h C o u n c il— C o m m itte e o n th e I n s titu tio n a l M e a n s for A s s e s s m e n t o f R isk s to P u b lic H e a lth (N R C C o m m itte e ) 1983. R isk a s s e s s m e n t in th e fe d e ra l g o v e rn m e n t: m a n a g in g th e p ro c e ss . W a s h in g to n D .C ., N a tio n a l A c a d e m y P ress. N e w to n , M ., a n d D o s t, F.N . 1984. B io lo gical a n d p h y sic a l e ffe c ts o f fo re s t v e g e ta tio n m a n a g e ­ m e n t. S e p te m b e r 24, S ta te o f W a s h in g to n , D e p a rtm e n t o f N a tu ra l R e so u rc e s, O ly m p ia . O ffice o f S c ien c e a n d T e c h n o lo g y P o licy (O STP) 1984. C h e m ic a l c a rc in o g e n s: re v ie w o f th e sc ie n c e s a n d its a sso c i­ a te d p rin c ip le s . F e d e ra l R e g is te r 49: 21595-21601. c\ O Human Epidemiology NEUROLOGICAL EFFECTS ----------------------- Cohort Studies----------------------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. Singer, Moses et al 1982 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 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 56 workers in a 2,4-D & 2,4,5-T plant were compared with 25 unexposed controls. 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 nonsignificantly reduced in exposed group. Sural nerve conduction was slightly reduced in unexposed. 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 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. ,ew of reproductive effects cf sins/ no definite conclusions. 2488 H-I43 H H u m an H ealth R isk A sse ssm e n t REPRODUCTIVE OUTCOMES * Cohort Studies Smith, Fischer, Pearce & Chapman 1982 548 sprayers in New Zealand and 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. Other Studies----------------------Nelson et al 1979 Cleft palate occurrence by county with herbicide use by county based on rice acreage. No association observed. Thomas 1980 Congenital malformation and 245-T use over time in Hungary. No association observed. Hanify et 1980 al New Zealand malformations in association with spraying herbicides by area and time. Mix>_-results Field &Kerr 1979 Australia - neural-tube defects ar.c spraying of 2,4,5-T over time.Milo positive association Balarajan & McDowall 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 Review of Vietnamese studies for both paternal and maternal studies Mixed positive results - no clear pattern Hatch 1984 Review of reproductive effects c-f dioxins/ no definite conclusions. 2489 H-142 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 . . >• > s v»'-' •' 1.2 Proportional Mortality Death certificate study/ 49 STS deaths/ looked at occupations with possible 2,4-D exposure including farming and forestry. > J k 9 ^ ** $ 3 0 O ' H-X41 H-141 F^ « S e TOXICÏTÏ/ POINT ESTIMATE OF RELATIVE'«1^- cmnv >1 _ Q COMMENT SOFT TISSUE SARCOMA (STS) -Cohort Studies--— -*------ -— — Lynge 1985 2.72 0.0 3.33 Based on 1 male case in pl­ acid manufacturing and pat Based on 0 female cases in] acid manufacturing and pac 'r 0.0 Based on 5 male cases. Based on 0 female cases. 5.19* 0.0 1.38 0.0 Zack & Gaffey 1983 Based on 3 male cases in manual services. v Based on 0 female cases in manual, services. Based on 1 male case in other chemical manufacturing and packing]' 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 Axelson et al 1980 Based on 0 male deaths. 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 Honchar & Halperin 1981 0.0 41.4’ Based on 0 male deaths. 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 H-139 P-3-513 H H u m an H ealth R isk A s s e s s m e n t i?? TOXICITY/ STUDY POINT ESTIMATE OF RELATIVE RISK >1.0 <=1.0 COMMENT NON-HODGKIN’ S Cohort Studies Riihimaki et al 1982 o o Based on 0 male deaths, AxeIson et al 1980 o o Based on 0 male deaths Ott et al 1980 o • o 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 Hardell, Eriksson et al 1981 ---------Case-Report-----------------------Pilot study of 17 cases. 14 cases had employment consistent with exposure (farming, forestry, sawmill, painting and building). --- 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 nonHodgkin '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 (4.80*) ( (1.71*) ) 576 cases and 694 random controls from the general population: ever 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 -1 3 7 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~& ?' J TOXICITY/ STUDY ■tau*.-. Human Epidemiology HODGKIN'S P O I N T ESTIMATE OF RELATIVE RISK >1 . 0 <=1.0 COMMENT -Case-Control StudiesHardell, 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 nonHodgkin'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 -I3 5 1 H H um an H ealth R isk A sse ssm e n t . TOXICITY/ STUDY POINT ESTIMATE OF RELATIVE RISK >1.0 <»1.0 COMMENT LEUKEMIA ■Cohort Studies Lynge 1985 Manufacturer Cohort 1.11 2.08 Based on 5 male cases. Based on 2 female case. 1.35 Based on 1 male case in phenoxy acid manufacture and packaging. Based on 1 female case in phenoxy acid manufacture and packaging. 4.0 Riihimaki et al 1982 Herbicide Applicators Axelson et al 1980 Railroad Sprayers Ott et al 1980 Manufacturer Cohort* 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 0.68 Based on 12 male cases. Based on 1 female case. 0.0 Based on 2 male cases in phenoxy acid manufacture and packaging. Based on 0 female cases in phenoxy acid manufacture and packaging. 0.63 Based on 1 male death. 0.0 PRM based on 0 male deaths among 2,4,5-T exposed workers. 1.36 Zack & Gaffey 1983 Manufacturer Cohort Riihimaki et al 1982 Herbicide Applicators 1.1 Based on 4 male deaths with ten year latency period. Axelson et al 1980 Railroad Sprayers 2.2 Based on 3 male deaths. 3.1 (6.1*) 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) Ott et al 1980 Manufacturer Cohort 0.0 Based on 0 male deaths with only amitrole exposure. 0.0 Based on 0 male death. * = Significant at the p=0.05 level. 2498 i?A5?1.0 <=1.0 COMMENT LUNG CANCER ■Cohort StudiesLynge 1985 Manufacturer Cohort Based on 38 male cases. Based on 6 female cases. 1.19 2.21 2.06* 1.28 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 Based on 14 male deaths. 1.68 PRM based on 6 male deaths among-'* 2,4,5-T exposed workers. . Riihimaki et al 1982 Herbicide Applicators 1.1 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 1.9 (2.9) Based on 1 male death with phenoxy acid and amitrole exposure (with a ten year latency period) 3.2 Based on 2 male deaths with only amitrole exposure. (with a ten year latency period) (2 . 6 ) Ott et al 1980 Manufacturer Cohort Based on 0 male deaths with only phenoxy acid exposure. 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------------------------0.99 0.88 Lynge 1985 Manufacturer Cohort 1.05 0.87 Zack & Gaffey 1983 Manufacturer Cohort 1.13 Riihimaki et al 1982 Herbicide Applicators Axelson et al 1980 Railroad Sprayers Ott et al 1980 Manufacturer Cohort 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. Based on all 35 male deaths. 0.82 PR M b a s e d on 9 male deaths among 2,4,5-T exposed workers. 0.71 Based on all 26 male deaths. 0.82 Based on 20 male deaths with ten year latency period. 1.4 Based on all 17 male deaths. 1.1 (1.9) 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) 0.28 Based on the 1 male death. ★ = Significant at the p=0.05 level. 2500 D -3-t>©( H-131 Human Health Risk Assessm ent H .-^¿r IV. Presentation of Epidemiology Studies by Type of Cancer Summaries of all cohort studies and relevant case-control studies are présented 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. -- ; -r i H -I3 0 \sP ^ Human Epidemiology Zack & Gaffey 1983 USA Manufacturer Cohort 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 Total observed deaths = 163 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 Ou et al 1980 USA Manufacturer Cohort 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. ^ 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. Total observed deaths = 11 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.t»65 H-129 Human Health Risk Assessm ent H 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 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 cancer incidence = 208 among 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. 200 individuals 9 o A H-128 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 o f 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 Human Health Risk Assessm ent H 3. Leukemia r 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. H -I2 6 O' yo 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. E v a lu a tio n s o f A s s o c ia tio n 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 2506 Based upon very small studies, there is a suggestion that exposure to phenoxy acids and/or dioxins may cause stomach cancer. H-125 Q-abo7 H Human Health Risk Assessm ent 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 etal, 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 . S tu d y D e s c rip tio n s 9 The studies evaluated include five worker cohort studies, a number of casecontrol studies, and a few miscellaneous studies. The worker cohort studies cL $ Vo H-124 2507 Human Epidemiology Observational Epidemiology I. Discussion A . S tr e n g th s & W e a k n e s s e s 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. T h e S c o p e o f th e S tu d ie s 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) S ection 6 Data for Evaluation of Human Epidemiology 2509 9 2510 O' Journal o f Rural Studies. V0 | 4. No 3. pp. 23«J-24T. IV8X i|7 j.l_ijifr m S3 m.i - ijuij Primed ui Great Britain 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 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). 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. 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). 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. 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 chemi239 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 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 241 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 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 243 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 Ê 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* P P b P Insecticide H erbicide Fertilizer M anufacturing M ining R uralily M ediatt family incom e M edian educational level Foreign slock A dju sted K l F -ratio —1» 129* 12.630» -1 2 8 6 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 -3 .4 9 0 -0 3 1 5 2.406 1.080 -6 .5 3 3 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 b P —4.646 7.009» -0 .5 2 9 -1 .5 0 7 - 1 640 0 223t -0.000 0 299» 1.308 0078 4.558» -0 .1 1 7 0 221 -0 .0 3 0 -0 .0 7 2 -0 0 1 8 0 134 - 0 046 0 149 0.046 R espiratory b P 57.488» - 1 9 151» -4 .2 9 8 -5 .6 3 5 23.610» 0.105 0 002» -0 .1 6 8 » -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 b p 3.463 21.529* -5 .4 0 5 » 8.690» 12.330» 0 140 0 001 -0 .7 1 9 » 42.850» 0.363 67.673* 0.026 0 216 -0 0 9 2 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). M »/> = SIMM. 02 p b V v tP=«=0.05. C. Shannon Stolces and Kathy D. Brace U rinary G enital V ariable Chemical Use and Cancer Mortality 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. 245 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. 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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 re b sfo r s c h u n g 80. 289-295. 2519 » J o -30*0-0 \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 O* 9^3-2- 2521 STUDY OF PESTICIDE GENOTOXICITY M ichael D. W a te rs ,1 Shahbeg S. S andhu,1 V incent F. Sim oon,2 K r is tie n E. M ortelm ans,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 r o 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 fundam ental problem in p e s ti c id e developm ent i s to produce chem icals t h a t a c t s p e c i f i c a l l y a g a in s t c e r t a i n organism s w ith o u t a d v e rs e ly a f f e c ti n g o th e r s . Because o f th e s i m i l a r i t i e s in th e s t r u c t u r a l , m e ta b o lic and g e n e tic components o f a l l l i f e form s, a b s o lu te sp e c ie s s p e c i f i c i t y i s fre q u e n tly d i f f i c u l t 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 f f e c t s beyond th o se f o r which th ey were o r i g i n a l l y m anufactured. 275 280 MICHAEL D. WATERS ET A L T able 2 . D e s c rip to r G en o to x icity B ioassays Employed Organism P ro p e rty Examined Point/G ene M utations in P rokaryotes R eference ■ a) à SAL* S. typhim urium (5 s t r a i n s ) Reverse m utation WPU* E. c o l i WP2 uvrA Reverse m utation (2) - Point/G ene M utations i n Eukaryotes YER S. c e r e v is ia e D7 R everse m u tatio n C27) L5T Mouse lymphoma L5178Y c e l l s Forward m u tatio n (5) SRI D. m elanogaster R ecessive le th a lity (25) . „ Prim ary DNA Damage in P rokaryotes REP* E. c o li polA D i f f e r e n t ia l to x ic ity (21) REV* B. s u b t i l i s ree D i f f e r e n t ia l to x ic ity (13) SAR S. typhimurium uvrB, ree D i f f e r e n t ia l to x ic ity (1) Prim ary DNA Damage in Eukaryotes (4) YE3* S. c e r e v is ia e D3 Enhanced m ito tic recom bination YEH S. c e r e v is ia e D7 Gene c o n v ersio n and c ro s s in g -o v e r (28) UDH* Human lung f i b r o b l a s t s WI-38 Unscheduled DNA s y n th e s is (19) , Chromosomal E f fe c ts see C hinese ham ster ovary c e l l s S is te r-c h ro m a tid exchange (16, 22) MNM Mouse bone marrow and c a rd ia c blood Chromosome breakage (m ic ro n u c le i) ( i7 ) DIM Mouse Dominant le th a lity (18) 25CG : *A b io a s s a y from Che i n i t i a l b a tt e r y o f sc re e n in g t e s t s . 9 -/¿ I ic h lo rfo n Compound P oint/G ene M utation P ro k ary o te Eukaryote SAL WPU YER L5T SRI. Ni *'T rr NT -.f tt 3 m __________ DNA Damage__________ P ro k ary o te Eukaryote REP REW SAR YE3 YEN UDH Chromosomal E ffe c ts SCC MNM DLM _____________________________________ ____ — ----------- ? £ C acodylic a c id v r c rr D i a ll a te IT Brornaci1 C. Z C Dicamba c » r Dinoseb DSMA +* Honuron + USUA P en tach lo ro p h en o l P ro p a n il Siduron Sim azine S u lfa lla te +* T ria lla te +* T riflu ra lin 2 , A-D 2.A-DB K tf a 2 , A, 5- T or ro _!------------------- o V c V vs\ t J MLDY OF PESTICIDE GENOTOXICIT Y 1SET, 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 a te d aro m atics (F ig u re 1 0 ). 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 o f c h lo rin a te d compounds; evidence of p o s it i v e e u k a ry o tic a c t i v i t y f o r th e 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 t e s t i n g i s in c o m p le te , 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 a ry o tic system , and fo u r p e s ti c 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 eu k a ry o tic system s (T able 12). The l a s t th re e chem icals in t h i s group have s im ila r s t r u c tu r e s (F ig u re 12) and a re c l a s s i f i e d as e th y le n e b is d ith io c a rb a m a te f u n g ic id e s . S ince th e d a ta in T ables 7 and 8 su g g est t h a t th e p o s i t i v e r e s u l t s o b ta in e d 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 eu k ary o tes. *•1 m te d Chromosomal Damage. A lthough th e i n i t i a l t e s t b a tte r y did not in clu d e t e s t s f o r chromosomal damage, nine p e s tic id e s (T ables 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 chem icals caused a p o s it i v e resp o n se f o r s is te r - c h r o m a tid 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 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 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, a cep h ate, demeton, m onocrotophos, and t r i c h l o r f o n , were p o s itiv 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 , c a co d y lic a c id , monuron, and benomyl, were p o s it i v e i n e u k a ry o tic 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 l e t h a l t e s t . S ix o f th e s e compounds were p o s it i v 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 e th y l-p a ra th io n , and m onocrotophos, th e h e rb ic id e b ro m acil, and th e fu n g ic id e s c a p ta n and f o l p e t . Comparison o f B ioassay and C a rc in o g e n ic ity Data A comparison o f th e g e n o to x ic ity t e s t r e s u l t s w ith c a rc in 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 e rb 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 fu n g ic id e (c a p ta n ) e v a lu a te d i n th e p r e s e n t stu d y cause tumors in 2525 9 -/j/ u KJ 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 Compound __________ DNA Damage_________ P rokaryote Eukaryote REP REW SAR YE3 YEH UDH C h lo rp y rifo s ( I ) - C hrysanthem ic a c id ( I ) - o -d ic h lo ro b e n z en e ( I ) - 2,4-D (H) - - t - - - 2,4-DB (H) - + - - - - Dicamba (H) - - + + - - - Dinoseb (N) - - + + + - - P ro p a n il (H) - - + + - - 2 ,4 ,5 -T (H) - - + - se c-b u ty la m in e (F) - + - - - + + - + - - + - - - - MICHAEL D. WATERS ET AI to OJT to cn> P oint/G ene M utation P ro k a ry o te E ukaryote SAL WPU YER L5T SRL 314 MICHAEL D. WATERS ET Al ci 2,4-DB Acid / \ Cl REP ci 2, 4, 5-T Cl. n \ ■0— CNj ----- C — OH CI REW F ig . 11. 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 MICHAEL D. W ATERS ET t Comparison o f G e n o to x ic ity and C a rc in o g e n ic ity T e st f'H R e s u lts P e s tic id e s G e n o to x ic ity Mice m/f P o s itiv e C a rc in o g e n ic ity Captan (F) C a rc in o g e n ic ity R ats m/f •M Ref. +: 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 te s ts + + d i) S u l f a l la t e (H) (m u ta g en ic ity t e s t i n g inco m p lete) + : SAL 4 te s ts +/+ +/+ (9) 7 te s ts - /+ T r i f l u r a l i n (H) ' (9) *Ì H u (9) P o s s ib le C a rc in o g e n ic ity +: L5T, YE3 10 t e s t s A zinphos-m ethyl ( I ) F en th io n ( I ) 5 te s ts P a ra tb io n ( I ) 8 te s ts ±/± (9) (9) ± /t/t (9) N egative C a rc in o g e n ic ity 4 te s ts (9) E ndrin ( I ) -: 6 te s ts (9) M alathion (1) -: 8 te s ts (9) 5 te s ts (9) D iazinon (1 ) M ethoxychlor ( I ) M e th y l-p a ra th io n ( I ) PCNB (F) ‘ v 2,4-D and e s t e r s (H) ; +: L5T, YE3, SCC 8 te s ts (9) 6 te s ts " (9) +: REV, REP 5 te s ts *• • (12) + = p o s it i v e re s p o n s e , ± = e q u iv o c a l, " = n e g a tiv e resp o n se (under c o n d itio n s o f 'b io a s s a y ; n o t n e c e s s a r ily n o n -c a rc in o g e n ic ). 2528 frtM Table 13. 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 exposure assessment that would tend to mute any exposure-re-' sponse effect. For example, acres sprayed is only a surrogate measure for delivered dose—a farmer’s use of herbicides in 1970 may not be representative of use in other years, and a large proportion of subjects are likely to have ceased farming since 1970. Third, the exposure information available in this cohort, although less than that available in case-control studies, would be less affected by accuracy of respondent recall, a major criticism of case-control studies. In the cohort study presented here, the Aaron Blair information on herbicide use in 1970 is probably reasonably accurate, but it is unclear how well herbicide use during this year represents farmers’ use in other 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 for certain '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 ' ethnicity i 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 softWigle et al. (9), through prudent use of readily available data V resources, have provided new information that supports the tissue sarcoma.-----7 : In this 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 or older, which provide further evidence that the use of herbicides have observed non-Hodgkin’s lymphoma associated with pheis associated with the risk of non-Hodgkin’s lymphoma. Mortal­ noxyacetic acid herbicides (3 -7 ) and, in particular, the phenoxyity 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, was impossible t&directly evaluate risks associated with potential 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 carcinogenicity of 2,4-D and 2,4,5-T in animals is inadequate insecticides. 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 relianceon —fositiv^and experimental evidence is not. :among:Jannax^en in.riris.cohort .study, 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. Received February 27,1990; accepted February 28,1990. Second, mortality from non-Hodgkin’s lymphoma rose signif­ Occupational Studies Section, National Cancer Institute, Executive Plaza icantly with increasing number of acres sprayed with herbicides, North, Rm. 418, Betfaesda, MD 20892. Herbicides and Non-Hodgkin’s Lymphoma: New Evidence From a Study of Saskatchewan Farmers 544 Journal o f the National Cancer Institute r 2% 2T 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 ( /) B l a b A, M alker H, C antor KP, e t a l : Cancer among farmers: A review. Scand J Work Environ Health 11:397-407,1985 (2) Bono GG, Boone« KM, C ook RR: Phenoxy herbicides and cancer Insufficient epidemiologic evidence for a ™ u i relationship. Fundam Appl Toxicol 12:172-188,1989 (3) H ardell L, E riksson M, L o w e r 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) H oar SK, B lair A, H olmes FF, et al: Agricultural herbicide use and risk of lymphoma and soft-tissue sarcoma. JAMA 256:1141-1147,1986 (5) W oods JS, P oussar L , S everson 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) P ersson B, D ahlander A, F redrdcsson M, et al: Malignant lymphomas and occupational exposures. BrJlnd Med 46:516-520,1989 . (7) L a V ecchia C, N egri E, D 'A vanzo B, et al : Occupations and lymphoid neoplasms. Br J Cancer 60:385-388,1989 (8) Pearce NE, S heppard RA, S mith AH, et al: Non-Hodgkin's lymphoma and fanning: An expanded case-control study. Int J r«nrw 39:155-161. 1987 (9) W igle DT, S emenctw RM, W ilkins K, e t a 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 A gency for Research on C ancer : Evaluation of carcino­ genic risks to humans. Overall evaluations of carcinogenicity: An update. IARC Monogr Eval Carcinog Risk l-42(Suppl 7), 1987 Better Cancer Treatment M eans Improved Survival Cancer Treatments: Consider the Possibilities An easy-to-read brochure designed to make patients aware of clinical trials as a treatment option. 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. 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: 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 _____ Cancer Treatments: Consider The Possibilities _____ What Are Clinical Trials AU About? Name________________________________________________ fWpnmrinr Address______________________________________________ I NCER ITUTE C iry. 2531 EDITORIALS 545 L 2. 2532 Environmental Health Monthly Voi. 2, NO. 6 March, 1990 ABSTRACT Editorial Review Board L o b M arie G ibbs A rlington, V A G ary G illen, M.D. Circleville, O H R obert G ln sb arg , Ph.D . Chicago, IL M arc L appe, Ph.D . Chicago, IL Penny N ew m an Riverside, C A Beverly Paigen, Ph.D . B ar H arb o r, M E David Oxonoft, M.D. Boston, M A Je n e tte S b e rm an , M.D. Alexandria, VA Managing Editor S tep h en L ester A rlington, VA Printed on Recycled Paper 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. Citizens Clearinghouse for Hazardous W astes, Inc. P.O. Box 926, Arlington, Virginia 22216 (703) 276-7070 2 534 13 Q' 1■ .. i • j t m+ y r \ ^ i1 I \ \ n \ , i i; ! !! *! ■r i i / » \ \ r \ 1 • . 1 5%7- I OF THE N A T I O N A L \ It****. ■>r n I! CANCER I N S T I T U T E &Esag&Bsa April 4, 1990\ Volume 82 Number 7 Contents Editorials News Commentary Review Articles In This Issue 541 Dose-Intense Adjuvant Treatment of High-Risk Breast Cancer G. Bonadonna, P. Valagussa 542, Herbicides and Non-Hodgkin’s Lymphoma: New Evidence From a Study of Saskatchewan Farmers A. Biair .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 - ,5 7 ° . .’. W* . .. 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 ’-'•575 .> 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 Highly Specific Prediction of Antineoplastic Drug Resistance With an In Vitro Assay Using Suprapharmacoiogic Drug Exposures D. H. Kent, L M. Weisenthal \.V •_:r 582’ 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-4 T. Reports •-r * * # 5 9 6 : Expression of the Progestin-Induced Fatty Add Synthetase hi Benign Mastopathie! and Cancer as Measured by RNA In Situ Hybridization ■ ' v—•¿;*r D. Chalbos, C Escot, C. Joyeux, M.-J. Tissot-Canyon, A. Pages, H. Rochefort -.Svci"; •*l J ’1 _. * 'if ?'*&■ a- ^ 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 Into Protein Matrix and In Vivo Localization in Normal and Neoplastic Tissues of Mice S. Rainer 2535 , 612 (Comenu continued on back cover) Q - 2 3 - - ■S 4 P-a-t,2>Cp V ^ B P - f f c a 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 -1 4 ). 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. In cases 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 R eceived June 2 6 .1 9 8 9 ; revised N ovem ber 27, 1989; accepted Decem ber 22, 1989. . Laboratory Centre for Disease C ontrol, Ottaw a, ON. Canada. W e thank Dr. David Bray, John Silins. M artha Fair, Deborah Jordan-Sim pson. and Christine Poliquin of the Health D ivision. Statistics C anada; Ray Bollm an, form erly o f the Agriculture D ivision, Statistics Canada; Dr. John Davies and Joan Lindsay o f the Bureau o f Chronic Disease Epidem iology, Laboratory Centre for Disease C ontrol. Departm ent o f National Health and W elfare; Diane Robson of the Saskatchewan C ancer Registry; and the Provincial Registrars o f Vital Statistics. • Correspondence to: Donald T . W igle, M .D ., Laboratory Centre for Disease C ontrol, Ottaw a, O N , C anada K IA 0L2. 2536 n Voi. 82, No. 7, April 4, 1990 ■5 ARTICLES V 'l Y Q ' ^ 575 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 number of 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 Farm Register 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 (1 7 ,1 8 ). 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 farm practices 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 After the Central Farm Register and the linkage of the Censuses of Agriculture and Population were preprocessed, records of i-» ^ . Journal o f the National Cancer Institute 2537 f-z fo -x -* T ab le 1. D istribution o f acres planted in m ajo r cro p groups. S ask atch ew an . 1971 % F arm s A c res Small groins 17,592 17,298 17,964 17,245 '1 3 0 1 0 -2 2 9 2 3 0 -3 7 9 380+ 25.1 24.7 25 .6 24.6 Hay and other fodder crops 4 5 .8 4 4 9,679 N one <30 3 0 -6 9 70+ 65.4 13.8 10.3 10.5 1222 7,354 Canola and mustard seed 46,2 3 2 8,902 7.632 7.333 N one <65 6 5 -1 1 9 120+' - 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 abic 2. No. o f farm s by % o f total area sprayed with herbicide and total farm size, S askatchew an, 1970* % total area sprayed T o ta l farm size (a c re s) 0 -4 9 5 0 -2 9 9 3 0 0 -5 9 9 6 0 0 -9 9 9 ,0 0 0 + All farm s T o tal 0 1-19 2 0 -3 9 4 0 -5 9 6 0 -7 9 80+ 9 58 (96.0) 4,963 (68.8) 11307 (52.2) 10,776 (46.0) 7,458 (44.3) 35,462 (50.6) 1 (0.1) 41 8 (5.8) 3,101 0 4 .3 ) 4 ,9 7 4 (21.3) 4377 (2 7 .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 ,0 9 6 (9.7) 1,761 (7 5 ) 1,015 (6.0) 5540 (7.9) "2 (0.2) 141 (2.0) 275 0 .3 ) 183 (0.8) 116 (0.7) 71 7 0 .0 ) 31 (3.1) 87 0 .2 ) 81 (0.4) 53 (0.2) 50 (0.3) 302 (0.4) 9 98 (1 0 0 .0 ) 7,216 (1 0 0 .0 ) 21 ,6 4 6 (1 0 0 .0 ) 23,405 (1 0 0 .0 ) 16,834 (1 0 0 .0 ) 70 .0 9 9 0 0 0 .0 ) * V alu es in p arentheses = % o f farm s. T ab le 3. O bserved and expected No. o f deaths am ong S askatchew an farm ers aged 35 y ears o r m ore. 197 1 -1 9 8 5 95% Cl C au se o f death O bserved Expected* SM R A ll cau ses in fec tiv e and parasitic A ll m alig n an t n eoplasm s S to m ach T ra c h e a , bronchus, lung C o n n ectiv e tissue M elan o m a “ P r o s t a t e .............. B rain L y m p h o id t N o n -H o d g k in 's lym phom as} L eukem ias§ M u ltip le m yelom a D ise a ses o f the circulatory system A c cid e n ts, 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 4 6 2 .0 9 3 .6 2 0 0 .0 112.1 156.2 68.5 7,895.5 1.098.7 0.74 0.41 0.81 0 .9 0 0.71 0 .8 9 1.06 0 .9 6 1.03 0 .9 6 0.92 0.88 1.02 0 .7 4 0.79 L ow er lim it U pper lim it 0.72 0.27 0.78 0.79 0.67 0.53 0.68 0.87 0.83 0.83 0.75 0.74 0.8 0 - 0 .7 2 0.74 0.75 059 0 .8 4 1.02 0 .76 1.40 1.56 1.05 1.25 1.10 1.11 1.04 1.29 —£ U 6 6.8 4 'E x p e c te d No. o f d eath s based on age- an d period-specific m ortality rates for S ask atch ew an m ales, 1 9 7 1 -1 9 8 5 . 1 1 C D (In tern atio n al C lassification o f D is e a s e d , 2 0 0 -2 0 3 . 4 1 C D 9 . 2 0 0 , 202. § 1 C D 9 , 2 0 4 -2 0 6 . 2 0 7.0, 2 0 7 .2 , 2 0 7 .8 . 208. Voi. 82, No. 7, April 4, 1990 2538 ARTICLES 577 T ab le 4 . A nalysis o f sociodem ographic variables and non-H odglcin's lym phom as, based on internal standardization, for S askatch ew an fanners aged 35 y ears o r m ore. 197 1 -1 9 8 5 95 % C l Person years O b serv ed d eath s RR* *§ 76.352 80.025 7 0 ,4 9 0 78,105 5 7 3 ,0 0 6 9 14 17 13 50 E d u catio n (g rad e s com pleted) 12+ 9 -1 1 <9 ' U nknow n 9 5 .6 7 2 162,916 4 6 ,3 8 4 5 7 3 ,0 0 6 M o th er tongue E nglish F ren ch G erm an U k rain ian O th e r 5 1 0 ,4 3 6 38.9 3 2 140,794 9 5 .177 9 2 ,6 4 0 V ariable L ow er lim it U pper lim it 1.0 0.77 0.60 0.84 0.43 0.38 0.27 0.41 0.25 1.54 1.31 1.76 0.74 12 30 11 50 1.0 1.15 0.88 0.52 0.59 0.36 0.28 2.24 2.19 0.98 51 3 22 16 11 1.0 0.78 1.43 1.56 0.96 0.26 0.86 0.89 0 .5 0 2.35 2.33 2.71 1.83 1970 Incom e (S) <1300 7 ,5 0 0 -2 3 ,9 9 9 2 4 ,0 0 0 -4 7 ,9 9 9 4 8 ,0 0 0 + U nknow n * 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 ab le 5. D o se-re sp o n se analysis o f 1970-1971 fa n n in g p ra ctic e s and no n -H o d g k in 's lym phom as, b ased on internal stan d ard izatio n , for S ask atchew an farm ers aged 35 years o r m ore, 1 9 7 1 -1 9 8 5 95 % C l F arm in g p ractice P erson years O bserved d eath s RR* A cres sp ray ed w ith herbicides. 1970T 0 1 -9 9 1 0 0 -2 4 9 250+ 438.341 112.446 197,199 129,992 46 14 28 15 D o llars sp en t o n p esticides. 1970t 0 1 -4 9 5 0 -1 0 9 110+ 3 9 4 ,3 2 2 150,443 170,616 162,597 D o llars sp en t o n fuel an d oil for farm pu rp oses, 1970§ 0 6 0 3 6 0 -5 9 9 6 0 0 -8 9 9 900+ 2 0 5 ,2 0 9 2 1 7 ,8 7 2 22 1 ,5 5 5 2 3 3 .3 4 2 ' L ow er limit U pper limit 1.0 l .l 1 1.47 1.34 0.62 0.94 0.74 2.0 0 2.41 2.38 44 15 25 19 1.0 0.88 1.49 1.19 0.49 0.92 0 .7 0 1.57 2.45 2.04 22 23 27 31 1.0 1.18 1.45 1.83 0 .6 6 0.81 1.03 2.13 2.55 3.25 * M a n tel-H aen szel R R estim a te adjusted for age a n d c a le n d a r 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 fo r tren d c h i-sq u are (1 df) = 5.78, o n e-sid ed P = .008. 578 2539 Journal o f the N ational 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 farm and 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 of joint 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 a b le 6. O bserved d eath s and RR* due to n o n -H o d g k in 's lym phom a 1 9 7 1 -1 9 8 5 , by farm size and acres sprayed w ith herbicides in S ask atch ew an , 1970-1971 A cres sprayed F arm size All farm s < 1 ,0 0 0 acres > 1 ,0 0 0 acres 35 1.0 11 1.0 46 1.0 1 -9 9 D e ath s RR (9 5 % C l) 14 1.31 (0 .7 1 .2 .4 0 ) 0 0 .0 0 (0.00, 2.85) 14 1.11 (0.62. 2.00) 1 0 0 -2 4 9 D eath s RR (9 5 % C D 28 1.92 (1 .18, 3.18) 0 0.00 (0.00, 1.01) 28 t .47 ( 0 .9 4 ,2 .4 1 ) 250+ D e ath s RR (9 5 % C D 10 2.14 (1 .0 5 ,4 .2 4 ) 5 0.60 (0 .2 2 . 1.68) 15 1.34 (0.74, 2.38) 8.32 .002 1.00 .159 2.31 .064 0 D eath s RR h i-sq u are for trend 'o n e -ta ile d ) * M an tel-H acn szel RR estim ate adjusted for age an d c alen d a r yr. V ol. 82, N o. 7 , April 4 , 1990 T ab le 7. RRs (95% C l) from m ultivariate Poisson regression analysis of n o n -H o d g k in 's lym phom a, restricted to farm s less than 1.000 acres, S ask atch ew an farm ers. 1 9 7 1 -1 9 8 5 V ariable fuel cost, 1970 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 N ovem ber 7 ,1 9 8 9 ; revised D ecem ber 1 8 ,1 9 8 9 ; accepted Decembe: 2 6 .1 9 8 9 . Supported by Public Health Service grant C M -57710 from the National Cance Institute. National Institutes o f H ealth. D epartm ent o f Health and Humai Services, and by the Veterans Adm inistration. O ncotech. 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 Jo u rn a l o f th e N a tio n a l C a n c e r In stitu t 9 - s i *■ ti I H 2544 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 i m 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. 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. Nonmedical expert witness w ith adequate train­ ing, education, and experience could express novel cancer-causation theories. Christophmen v. AUied-Signal Corp., 902 F.2d 362 (5th Cir. 1990). Expert’s testimony was admissible despite the lack o f epidemiological evidence linking chemical ex­ posure to colon cancer. 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- 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 33 LAW REPORTER 373 2545 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 proof was 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, see Drnlttn 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.) 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.] F a 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. Expert’s failure to use a specific term did not pre­ clude a finding th a t 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 NOVEMBER 1990 374 33 LAW REPORTER 2546 a * . * 2547 I I 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 o f cancer at four factories m aking phenoxy herbicides NOTICE D avid Coggon, Brian Pannen, Paul W inter Abstract To assess the possible carcinogenicity o f phen­ oxy herbicides and related chlorophenols and dioxins, the International Agency for Research on Cancer is coordinating an international collaborative study o f workers exposed to these compounds in their production or use. Four B ritish cohorts o f chem ical manufacturers which have been recruited to the survey are described. They comprise a total o f 2239 men em ployed during 1963-85. These subjects were traced to 31 Decem ber 1987 through the National Health Service Central Register and the National Insurance Index, and their m or­ tality compared with that in the national population. Two deaths were from nonHodgkin’s lymphoma with 0-87 expected. Both deaths occurred more than 10 years after first exposure to phenoxy compounds. One further non-Hodgkin’s lymphoma was registered in a living subject with probable exposure to phen­ oxy compounds. No cases of soft tissue sarcoma or Hodgkin’s disease were recorded. A non­ significant excess o f lung cancer (19 deaths observed, 14-2 expected) is probably attribut­ able to chance or a confounding effect of smoking. In one cohort only there was increased m ortality from circulatory disease (34 deaths observed, 20-4 expected). A nested case-control study did not point to any occupational cause for this excess, but further evaluation will be needed during continued follow up. The regulation of pesticides requires that the utility of products be balanced against any risks to the environment and to the health of manufacturers, > I M R C E n v iro n m e n ta l E p id em io lo g y U n it, U n iv e rsity o f S o u th a m p to n , S o u th a m p to n G e n e ra l H o sp i­ ta l , S o u th a m p to n S 0 9 4XY D Coggon, B Pannen, P W inter j THIS MATERIAL MAY BE PR0TECTE9 ETY COPYRIGHT LAW TITLE 17 U.S. C00E users, and those eating contaminated foods. Judge­ ments about the toxicity of new compounds in man 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 directly. Such assessment is important because laboratory investigation may not always reliably predict toxicity in man. One group of compounds that have attracted particular attention are the phenoxy herbicides (for example, 2,4,5-trichlorophenoxyacetic acid (2,4,5T), 2,4-dichlorophenoxyacetic acid (2,4-D), 2 methyl-4 chlorophenoxyacetic acid (MCPA)). Dis­ covered in the 1940s, these chemicals have found extensive worldwide use in agriculture and forestry, as well as being sold on a smaller scale for domestic application in gardens. Initial case-control studies in Sweden suggested that exposure to phenoxy com­ pounds and structurally related chlorophenols might carry an increased risk of soft tissue sarcoma12 and lymphoma.’ This idea was supported by the findings of four cohort studies of chemical manufacturers in the United States.4"7 Subsequent investigations, however, have been less conclusive.*"22 Several have shown associations between the manufacture or use of phenoxy compounds and soft tissue sarcoma or lymphoma, but risk estimate's have been smaller than in the earlier studies and usually not statistically significant. The statistical uncertainty surrounding small increases in risk for rare diseases presents a problem in evaluation. To help resolve this issue, the Inter­ national Agency for Research on Cancer (IARC) has established an international collaborative survey of workers exposed to phenoxy acids and related com­ 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 relevant not only to the assessment of phenoxy compounds but also to other chemicals that have been manufactured and formulated at the same factories. ’•**- »■», fr ' 41 ■'äfcl' 1 Coggon, Parnell , W inter 174 Toiie 1 D efinition o f cohort sa •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 A 2,4,5-T 1968-78 2.4D and 2,4-DP 19542.4DB 1965 MCPA and MCPP 1954MCPB 1970PCPA and PAA (produced only) 1969 - Picric, add Dinitro-o-butyl phenol Diaitxo-o-cresol Simiaxte Aminotriazole Oxynils B 2,4,5-T (formulated only) 1970-74 2,4-D, 2,4-DP and 2,4-DB 1969 MCPA and MCPP 1969MCPB formulated 1969 produced 1975 - C 2,4,5-T (formulated only) 1959-81 2,4,-D (formulated only) 1959-81 MCPB 1956PBA (produced only) 1958-75 Factory D 2.4.5T (formulated only) 1960-79 2.4D 1949 2.4DP 1955MCPA 1951 MCPP produced 1955formulaied 19652.4.6-TCP (produced only) 1983- Number o f men analysed Number of All manual employees during April 1975Octobcr 1985 1104 1062 Dithiocufeamates Organophosphorus compound* Carbamates Disocap Toluidine compounds Urea herbicides Imidazole compounds Phthaizmide compounds All weekly paid employees during March 1969Novembcr 1985 271 261 Amuopbyliine Metronidazole Sulpbonas&ides 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 345 343 Metallic soaps Plaiddser eaten Naphthenic add Alkyl phenols Phthalate esters All weekly paid employees during April 1969Dccember 1985 519 503 traced (3) All maintenance workers during July 1967December 1984 •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-DB«2,4dichiorophenoxybutyric 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 I I I M oriaiity and incidence o f cancer al fo u r factories making phenoxy herbicides T able 2 ■ 175 O bserved a n d expected m o ria iity by cause: a ll subjects A nalysa based on national rases Expected numbers locally adjusted Cause o f death Deaths observed Deaths expected 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 SM R 95« C l Deaths expected SM R 95« C l 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 T able 3 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 M o r ta lity b y fa c to ry fo r selected causes Factory A Factory C Factory B Factory D Cause o f death Deaths observed Deaths expected Deaths observed Deaths expected Deaths observed Deaths expected Deaths observed Deaths 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 17 5 1 3 5 3 0 11-90 5-29 1-25 1-43 2-83 0-99 0*07 22 12 0 3 6 4 1 30-13 14-31 2-33 2-59 8-34 3-22 0-20 51 23 6 6 14 6 1 49-50 23-75 4-79 3-48 13-42 5-30 0-29 Expected numbers are based on national rates. 2550 m ■XW" .......... .. ....... J-'*~ ----- ^ .v ..--,. - - C oggon, P a rm en , W ittier 176 T7D»-0*CS ECO^'EP :fjlrf!'-r?CO April 25, 1991 Marvin Legator, Ph.D Dept, of Preventive Medicine & Community Health U.T.M.B. 24 KEILLER-F19 Galveston, Texas 77550 Re: fax 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 thé 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, 1 9 7 4 , 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, V 0O' LhQ¡f\tO. 2563 EXHIBIT _ _ / M. HËKfDfefCKS A {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 15 :Cl h PR- « F^QM Lh U ÜFr !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?9i 15 :Q:Z FF.OH L h I-'I O F F I C E ^0 14097615172 p_ CHRONOLOGY Newman/AT&T 7-20—SO 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. - -65 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. 2-23-72 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.] - -72 Maude noticed a purple substance had drained onto ner property from AT&T's property. 3-25-74 AT&T contracted with Kem-Xil for vegetation control on 6,400 sq. rt. 2-20-75 AT&T & Kem-Kil contracted to spray 6,400 sq. ft. for vegetation control. 3-31-75 AT&T entered into a contract with vegetation control on 9,600 sq. ft. 4-26-75 AT&T contracted with Kem-Kil for vegetation control Of 9,600 sq. rt. 3-17-77 AT&T sprayed with their "in house" cnemicals soraved are not Known. - -77 Kem-Kil for employees, 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. & Kem-Kil enter into a contract for vegetation control. Denton is not included. 4/7 7 AT&T 3-16-77 Texas a &w concluded that tree had died of herbicide poisoning. 2566 p. a.tfc'l iiPF-X?-!??! rrCf' 1 Lh I.'J CFr!CE TO lSI1-!' P.0to 6-6-77 AT&T made a settlement with Floyd and Jean Halbert in the amount of $300. AT&T agreed it would not spray again. 3-28-78 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 AT&T contracted with Kem-Kil to control of vegetation. 12-4-80 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- AT&T contracted with Kem-Kil to spray 9,600 sq. ft. for the control of vegetation. -32 Spring 1982 spray for the 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 Dog was euthanized. 10-5-32 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, -22567 discharge diagnoses were: Diabetic ketoacidosis, Candida vaginitis, acuta sinusitis, hypoglycemia. 1- 33 2- 7-83 Dr. Gruaaro Garza performed several blood and urine tests on Wesley Patton Halbert. 3- -83 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. Wesley Patton Halbert suffered poor muscle coordi­ nation, extreme fatigue, headaches, nausea, and mononucleosis. Trisha 10th grade; took Standford Test of Academic results showed she regressed back to the 8th grade level. 1-9-34 Trisha and Kippie put on homebound school. 3-27-84 Results of Standford test lower than previous year. 3-28-84 Trisha diagnosed as chemically sensitive. showed Kippie scored 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 shaft. Wesley's penis 9-5-84 Wesley had to have his appendix removed. remarked appendix is unusually large. Dr. removed warts on 2568 h P 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. "appendix unusually large." 12-30-87 Trisha has genetic screening. 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 Tony aborts baby 24 weeks into pregnancy because of abnormalities,’ with clinical history of renal agenesis demonstrated by sonography. 5-5-33 Trisha's baby, Megan, has surgery for hydrocepha­ lus. Dr. remarked All genes normal. 2569 p-a.ti.1o 3/90 Megan’s collar bone not connected. 5/90 Maude R. Newman, chemically seeing Dr. William Cudd. imbalance, started K. 3-4-90 Kippie delivers baby girl, Randi Ashlynn cissna. 2AG/N03002.C7 -5- 2570 TOTAL P .09 /? 2571 , o RECEIVED JUN 1 3 1991 M-C-T, INC. Toxicology Consultants Mutagens - Carcinogens - Teratogens General Toxicology I.D. #74 212 4899 7 0 Colony Park Circle Galveston. Texas 77551 Telecopier - (409) 744-6369 y i o S ’.ooa-' M. Legator, P r e s id e n t 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; Dear Ms. June 11, 1991 MAUDE NEWMAN ET AL V AT&T Conwell: The following is an invoice for services rendered in the above referenced matter: RES EARCH AND CONSULTATION 1 1/2 DAYS (S3.000/DAY) $4,500.00 Yours truly 2572 2573 FILED No. 82.-4966-A 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. 1991 JÜL 15 AM 9:^8 § § § § § § § § § § § § § 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. AT&T of said incident. Plaintiff Maude R. Newman notified Defendant 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. -132584 / V 8* .9v< 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. chemicals may also attack the heart and liver and other organs. Such 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. suffer these symptoms for several weeks. He continued to 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 10/3/84 4/10/85 R. S. Croissant, M.D. R. S. Croissant, M.D. 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 23.4 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 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