Document vVrapr9pZMBxNNa0VzXNL1jDE

DEPARTMENT OF HEALTH, EDUCATION, AND WELFARE TRANSCRIPT OF PROCEEDINGS OF THE INTERAGENCY MEETING ON POLYCHLORINATED BIPHENYLS (PCBa) Thursday, August 5, 1971 Dr. Dale R. Lindsay, Associate Cocaiissioner for Science, Food and Drug Administration Chairman HONS 068058 .y [ |. |jj pj rvyawpywgjpprjrr' TRANSCRIPT OF PROCEEDINGS OF THE INTERAGENCY MEETING ON POLYCHLORINATED BIPHENYLS (PCBs) MCNS 068059 ATTENDEES COUNC11, ON ENVIRONMENTAL QUALITY Dr. Warrer R. Muir DEPARTMENT OF AGRICULTURE Dr. George F. Fries Dr. Fred J. Fullerton Dr. Philip C. Kearney Dr. Kenneth M. McEnroe Dr. William S. Monlux Dr. Harry C. Mussman Dr. Jack R. PI Inane r Dr. Robert C. Riley Dr. Frederick R. Sentl Dr. Joseph S. Stein DEPARTMENT OF HEALTH. EDUCATION AMD umP, Center for Dlaeaae Control Mr. William F. Barthel Food and Dior Administration Dr. Frank N. Allan Miss Helen C. Barry Dr. Nichols H. Booth Mr. J. William Cook Mr. Paul E. Cornelluaaen Dr. William D.'Aguanno Mr. Reo E. Duggan Mr. Hyman P. Eiduson Mrs. Mary K. Ellis Mr. John D. Findley Dr. Donald F. Flick Dr. Gerald B. Cueat Mr. Leroy Houser Mr. Kelvin H. Keath Dr. Albert C. Kolbye Dr. Herman F. Krayblll Dr. Dale R. Lindsay Mr. Donald R. Martin Mr. Joseph J. McGuire Dr. H. Dwight Mercer Dr. Murrell P. Morris Mr. Leasel L. Ramsey Mr. Lavefa R. Shelton Dr. Kenneth E. Taylor MGNS 068060 Food and Drug Administration (Continued) Hr. Robert A. Tucker Mrs. Berber* Ven Seholck Mr. Henry L. Verhulst Mr. John R. Westel National Institute of Environmental Health Science Dr. Lawrence Fishbeln Mr. William W. Payne Health Servlcea and Mental Health Administration Dr. Vincent F. Maturl DEPARTMENT OF INTERIOR Dr. Eugene H. Dustman Mr. Robert G. Heath Mr. Bernard M. Mulhem Dr. Lucille F. Stickel ENVIRONMENTAL PROTECTION AGENCY Mr. Virlyn W. Burse Dr. Morris Cranmer Dr. Thomas W. Duke Dr. Douglas Hammer Dr. Renault! D. Kimbrough Dr. Douglas Worf NATIONAL OCEANIC AND ATOMOSPHERIC ADMINISTRATION Mr. Themes C. Carver Dr. John A. Qnerson Dr. Joseph H. Soares OFFICE OF SCIENCE AND TECHNOLOGY Dr. Edvard J. Burger, Jr. NON GOVERNMENT Dr. Richard S. Gordon Dr. Thomas J. Haley Dr. J. R. Harris Dr. Roger A. Hoop ingarner Dr. Norton Nelson Dr. Lawrence M. Rosllnski MONS 068061 1 PROCEEDING^. DR. LINDSAY: I am Dale Lindsey, Associate Commissioner for Science, Food and Drug Administration. I apologise to everyone here for the catch as catch can nature of this meeting. In discussing this lets lest weelc with the Commissioner, he indicated chat he thought it probably would be a good idea to exchange information between the agencies that ere involved. The effort wes eo hurried thet besides Agriculture, EPA, end FDA, I are not sure whether we have other egencies here or not. Aa we go through the program anyone who has anything to eey -- and I would ancouraga you to have something to say ~~ please Identify yourself by name and where you ere from, for the benefit of our Stenotypiat who Is keeping e record of this meeting today so that all of us may know what happened and hopefully there won't be any argument about who said whet. There le soma problem, of course, about s meeting with as many technical terms as will be used here today. I hove asked the gentleman to use his best phonetic spelling and we will try to be aura that ve can fill In for what he may .not be familiar with. There ia no program, no agenda other than the agenda I have discussed with representatives of the agencies we have calked to. The Idea Is to exchange Information and I thought that probably MQNS 068062 2 Che best tey to do this would be to ask each agency with a problem Co give a situation report of that agency's problems or their findings. You don't have to tell us what you think you are going Co do. Ue will leavt. chat entirely up to you. The idea here is to identify interests, abilities to cope and to come up with soma sore of a better ides of who is doing what and what yet needs to be done and where it might be done. 2 think In the interest of time, since we are running late, 1 would like to have Dr. Sent! present the Department of Agriculture's position reports. DR. SENT1: Thank you. Dr. Lindsay. As Dr. Lindsay has said, our meeting has been put together on rather short notice. Ue haven't had much preparation for anything like a formal presentation. However, ve do have some people who can report on some of the things that are going on in the department. We thought probably it would be good to start out with a report on the situation that has focused attention on PCBs in the>last few weeks, and that relates to the finding in our poultry inspection service. . We have asked Dr. Stein, who is coordinator of the PCB work in that inapection service, to discuss it and give you a report on the monitoring program in the meat Inspection service. Dr. Stein. DR. STEIN: As Dr. Senti has said, this was very unexpected for me to be up here this morning and talking about this. The only data that I have with me are up In the top of my head. 1 have been rather closely associated with this project for about two weeks now. MCNS 068063 T nr 3 } think maybe if 1 just tell you how it came to our attention and what vc have done up until now, it might be helpful to you. * Ve found out about thla on July 19, which was two weeks ago Monday, l/e found out about it from representatives of Holly Farms in 'I North Carolina, who told ua that they had been having hatchabllity problems with their breeding fleck. The hatchabllity was down very low in some cases. As 1 gathered the information, they had done a lot of examination and testing to try to determine whet their problem was. * They had pinpointed fish meal and PBCs In flab meal. They than had called thla to the attention of Monsanto, who 1 understand then contacted the Food end Drug Administration. la that right, Mr. Duggan? MR. DUGGAN: That's right, right after noon. * DR. STEIN: On Monday, July 19, the poultry producers' representatives were In our office talking about it. At that time I don't think anyona knew what the reel extent of the problem was, although it was known that other people in the area had hatchabllity problems 4 and therefore probably used some of the same feed. 1 forget how thla came about but somehow we got an under standing that Food and Drug was Investigating the fishmeal plant and was going to furnish a list to us of the other purchasers of the fishmeal. We didn't really feel that we hed enough information at that time to do anything dramatic on a national scale. We wanted to learn more about the nature of it. We waited to get the list, which was furnished to us on July 22, Thursday of that week. It turned out there were 64 prime customers of the fistvncal plant, most of whom we could identify as being 1 MQNS 068064 integrated poultry producers. 'At that time vc sat down quickly with a small staff and decided what we were going to do. It looked like it was covering 12 states end many people. The poultry integrators, as you know, sometimes have hundreds of growers working for them individually. We came to the conclusion that it would be impossible with the laboratory facilities available and other llmitationa to teat all the birds involved. So we decided to try to find out as quickly as we could what the situation was. . Our plan called for taking multiple samples of all types of poultry and swine from every plant that was working under federal inspection in the areas Involved. In the meantime we found out that in two of the states, Arkansas and Indiana, which had been listed as prime purchasers, the plants or the purchasers in those areas did not use the fishmeal for livestock feed. One returned it because they had examined it and found it had PCBs In it and one used the fishmeal for preparing fish faad and also laboratory animal food. They didn't use it for livestock feed. So we had 10 states involved and approximately 180 poultry plants and, as 1 recall, 30 or AO swine slaughter plants. We set up our program. We told our people on Friday, July 23, to begin that day to pick up samples to send to our laboratory in Washington and to our laboratory in San Francisco. We gave them instructions on how to take the samples, pack, them, keep them in dry ice. We tied our labs all primed and ready to go and the samples begain arriving over the weekend. HONS 068065 A n*mjJi*it**L*.*, - - - **-**' 5 We began to get analysis about the 27th. During whet we would cell the CRASH teeting program, yesterday we had hed reports on 383 sanples. They include turkeys, broilers, layers and hogs. We have not this morning, to my knowledge found a sample chat exceeded the administrative guidelines established by the Food and Drug Administration, which is five parts PPM in the edible tissues of the bird. We began to be a little encouraged by our findings by the middle of the receipt of the samples but we couldn't be complacent because we had not concentrated on what could be the biggest problem, and that is the breeder fowls which were the cause of the knowledge in the first place, and layer fowls, both of which are kept much longer than broilers. In the meantime 1 should say we have found out that fisltmeal la not a big Item in hog feed. It is used to some extent but not like with poultry. So we set up last Friday a plan to con centrate on layers and breeders. We went back to every plant in the 10 states and told them to take samples from up to 10 lots daily of those that were slaughtered beginning Friday and going up through this week. They wouldn't take 10 samples if they didn't kill 10 lots, but 1 believe some killed that many. Those are being sent in to our laboratory right now. At the moment we have had no results on those latest samples. We plan to do continuing testing on broilers and we also plan to do some more tests on hogs. HONS 066066 ihfljViaiii ' IT iHr ili 6 When this first happened ve v^nt beck end checked our records of testing. We have been screening our routinely collected chlorinated hydrocarbon samples for PCB since about January. We had some problem with PBCs in another state at that time. We found in our records 1 think one sample that showed low level PCB8 somewhere about March or April out of a few hundred samples ve had screened for chlorinated hydrocarbons. We are continuing to screen our regular monitoring samples for PCBs and as 1 say, we will be continuing on an expanded basis to test samples. 1 don't know what ve will do until we get results on breeders. That la where, we are now. l didn't give you a lot of details, but 1 think that brings you up to date on what we have done. Let me first ssk if my co-workers want to add anything to what 1 have said. DR. KIMBROUGH: - Since the hatchability seems to be important, have you analysed any eggs or are you planning to? DR. STEIN: We have not analyzed any eggs. 1 think that question would better be put to Mr. Duggan. MR. DUGGAN Yea, we are analyzing eggs. DK. STEIN: You probably read In the paper that a number of birds were destroyed. They were destroyed on the Holly Fsrm down in North Carolina and they were destroyed on the basis of pretesting of live birds that Holly Farm was doing through a private laboratory. We have found very high amounts In some live birds *CNS 068067 7 present there. Some of them have been over the administrative guideline. Fortunately, those birds having that high amount were caught alive, killed and burled on that farm without being brought to slaughter. DR. BURGER: Would it be worthwhile to simply have quickly reviewed the Incident that led to the contamination of this feed, if it la known? DR. STEIN: I could tell it but I am not the one to do it. Mr. Duggan could do a much better job. His people did the review. All 1 know Is what 1 have read in the paper and then 1 talked to Mr. Duggan. I would be very delighted to have Mr. Duggan tell you about it. I can tell you what I know but he can tell you better. Are you willing to wait until Hr. Duggan takes hia turn up here? DR. BURGER: Yea. DR. FRIES: 1 was wondering If you hed identified which this was. MR. DUGGAN: I didn't plan to get into that but we have talked to the Monsanto people and they tell us, as its humanly possible, they have made that 100 percent 1242. We have heerd some rumors it might be just a portion of it bur they said that particular food is as perfect as they can make it, although not 100 percent. DR. STEIN: Are there any other questions? MOhlS G66063 --(r 1 riUifraiifin fj Thank you very touch. DR. SENT1: ' Another pert of the Department's activities relates tc work In the state experimental stations as related to our Cooperative State Research Service, particularly the research that is going on there. Dr. Riley of our research service will give a brief review of the activities In the experimental stations as they relate to PCB. DR. RILEY: Thank you. Dr. Sentl. I would like to discuss in broad outline some of the work in the State Agricultural Experimental Stations related to PCB. * Ve have pesticide residue laboratories In each of the 50 states. These laboratories are coordinated by regional projects in each of the four regions. There is federal participation on these regional residue projects. CSRS hss submitted names of key persons who are involved in this PCB situation.' Time has not permitted bringing many of these people in for this meeting. Frequently progress reports shown on USDA-CRIS-project printouts do not mention the work in a specific area such as PCB. For example, regional project W-45 has emphasised for several years coordinated research on chlorinated aromatic pesticides and PCB has received concerted attention. Dr. F. A. Gunther, at Riverside, California, has served as a clearinghouse for PCB samples to the participants of the Regional project. CalifornisrDavis is studying the photo-decomposition of PCBs. Colorado is studying the occurrence *0NS 068069 of PCB in tower sludge end che breakdown of PCB in sludge when It Is applied Co Che soil. Nevada is looking sc che Influence of PCB on enzyme sysCems. Hawaii Is working vlch che Influence of PCBs In semi-tropic climate. California-Riveraide has developed a carbon-skeleton chromatography method of separating and analysing PCB in the presence of DDT (J. Agr. Food Chem. JL9, 396-398 (1971)). Also they are working with che fate of PBCa in the soil. They have a soil bank of 150 soil types, and are working with PBCa in six representative soil types. Intldently, they are finding thac PCBs are quite persistent in Che soil. Scientists at Callfornla-Riverslde are also working with PCBs on vitamin D metabolism, calcium transport and calcium deposition in eggshells. In addition, che influeme and effect of PCBs on parasite and predators, storage in fat, and biological magnification are being examined. Similar research on PCBs is being conducted under a regional projact in the northeastern region. Cornell University is concentrating on PCBs in printers' ink, in newspapers and the relationship of recycling newspapers into food containers and movement of PCBa Into the food chain. There is considerable feeling that the burning of newspapers may be s mechanism that PCBs are widely distributed in the environment. The Geneve, New York station is working on PCBs in fish. Wisconsin has rather comprehensive work in the influence of PCBa on wildlife and some very specific projects are elmed et pinpointing MONS 068070 10 these influence*. I am happy to sec Roger Hoopingarner and Dr. J. H. Harris here from Michigan and North Carolina. I am sure they will tell us about the work on PCBe in their respective states. There are a few examples of the research being conducted at State Agricultural Experiment Stations and do not reflect a comprehensive survey of the vork. Moreover, much greater productivity can be accomplished within the framework of the pesticide regional projects and related wildlife and animal research if additional emphasis is placed upon this problem. Thank you very much. DR. SENT!: Z think that Just about covers in broad outline the kind of thing that la going on In the Department. Ue have an ARS In our pesticide residues analysis. Ue have baen concerned with PCB as it interfarea with the analysis for othar chlorinated hydorcerbona but 1 don't know that we need to speak to that at this moment. . >k If we get into problems of analytical methodologies this may arise. At this point 1 think I will turn it back to you, Dr. Lindsay, and perhaps you can enlarge some of the questions that have arisen in the discussion. DR. LINDSAY: Thank you. Dr. Sentl, and other members of the Department of Agriculture. 1 think it's probably appropriate to say at this time, since I forgot to say It earlier, that you will have the privilege of all good Washingtonians of extending and modifying your remarks. Ue will hsve a record of this early next week, 1 believe. 4 MONS 06SC71 & 4 i We will send the record around to the participants and you can taka that opportunity than to clean up anything that you may have misspoken or feel that you would like to change. When that is done, we will then distribute it to all the participants here for your further reference. 1 am not trying to take notes like 1 normally would because 1 am planning on getting a much better job from our Reporter. The logical agency to follow, 1 think, would be FDA. However, Dr. Duke of EPA is with us for a brief period because he has another meeting that Is In progress right now, so 1 would like to change the arrangement around and ask others who may be apeaklng for EPA to see If they would like to move in at this particular Juncture. EPA has not quite reached the tame acme that Agriculture and FDA have at the moment of never being able to do anything right so we will sandwich them in between the villains. We will let Dr. Duke make his presentation now and then he can catch the shuttle. Dr. Duke? DR. DUKE: I am Thomas Duke from the Environmental Protection Agency, Office of Research and Monitoring, Gulf Breeze Laboratory. I would like to mention at the beginning that there is other wprk going on within EPA, some of which you will hear about. Also there is some other aquatic work going on at EPA's Duluth Laboratory. I am going to speak only about data we obtained on PCBs in particular Aroclor 1254, at Gulf Breeze. MOMS 068072 12 We have had fish kills In the Pensacola area and when this occurs we usually check dead fish far pesticides residues and related compounds. In the summer of 1969, ve detected PCBs in some fish that were brought In. To make a long story short we traced the PCB, Aroclor 1254, to the effluent ditch of the Monsanto Chemical Company on the Escambia River. The contamination reportedly reached the river through a leak In the heat exchange system of the plant. The Aroclor 1254 flowed from their effluent ditch into the river and subsequently into the sediment and animals of Escambia Bay and the water of the Escambia River. I have some slides and it might be helpful if 1 went over these quickly with you. This Is a map showing the subject area near Pensacola, Florida. (Slide.) You will notice the location of the Escambia River and Escambia 'Say. The Aroclor 1254 entered the Escambia River approximately six miles from the bridge at Station No. 2. We detected it in fish, as I said, that wars brought in as part of a fish kill. We do not believe that the Aroclor 1254 In the effluent caused the fish kill. The cause of the kill was later shown to be a lack of oxygen, but at this time we did pick up the Aroclor 1254 reeidues. Subsequent samples showed Aroclor in other components of the system. (Slide.) This table shows you some of the levels of the Aroclor 1254 that occurred. These data are for croaker, menhaden and pinfish. HONS 068073 . -i. 13 In another sample, flounder liver contained approximately 76 ppm, shrimp, 1.5 parte per million. In sediment from the bay we found 1.7 parts per million. Sediment from the river outside the weir at the Monsanto plant contained approximately 400 ppm. I will now back up to the original slide. (Slide.) Xn 1969 we sampled the sediment from the river to Station 4 and ve have that data. Levels of Aroclor 1254 reached approximately eight parts per million in the lower area between Stations 4 and 5. In December 1970, we conducted another survey in which ve started at the Escambia River and went across the bay to the inlet to the Gulf of Mexico. At these stations we took duplicate top and bottom water samples and grab samples of sediment and also some core samples. To give you Just a general idea of the levels Involved, at the Monsanto weir -- this is in December of 1970 -- ve found 55 parts per million in bottom sediment. This is compared to the 400 parts per million ve found in 1969. 1 hesitate to compare the content of PCB in thes* sediments because the amount of PCB in the sediment depends upon the sise and chemistry of the sediment particle. The finer organic settlements have more PCB then the sand-sized grain. We have a shifting situation up there and I am not certain that our two grab samples contained sediment of exactly tha same composition. During the December 1970 survey, we found 18 parts per million in sediment between Stations 2 and 3 (on the map) and 7.2 ppm at Station 5. HONS 068074 14 We found (race amounts, somewhere around .05 parts per million, in sediment near Station 6 and then surprisingly in East Ray, off the map here. About four miles up Hast Bay ve found traces of PCB In the sediment and also under the Bay Bridge in Pensacola Bay. This was in December of last year. We did find one part per million in the water outside the weir. This was attributed to leaching from the sediments in the weir. Since that time, Monsanto has shut down that effluent ditch and diverted their effluent through a new ditch. We sampled Just lately and we did not find levels of PCB in the water or at least if they are there they are below .01 parts per billion. In December, 1970, we also took some core samples. Outside the weir, the core sample showed 76 parts per million of PCB on the surface; 30 parts per million^two to four Inches below the surface; six parts per million, four to six inches below the surface; and .4 parts per million, eight, inches below the surface. In Pensacola Bay at Station 5, we took more cores. As an example, one core contained Aroclor 1254 at these levels: Zero to two inches below the surface, 10 parts per million; eight to ten inches, 18 parts per million; ten to twelve inches, 1.2 parts per million. We still find PCBs at the 1 to 2 parts par million whole body range in some animals from the bay. I think the general trend is that we are seeing some loss of PCB compared to our 1969 samples. We are also doing some laboratory work on the toxicity of Aroclor 1254. MGNS 0660 75 15 I should mention first that ;e have several investigators working on this at the laboratory and I am presenting the data of several people. (Slide.) This slide shows some of out earlier work. Just to give you an idea of the toxicity. Here we are working at 5 parts per billion of Aroclor 1254 in the water. This material is insoluble so we are using acetone as a solvent and maintain acetone controls for comparison. You can see et 5 parts per billion we get 72 percent mortality in shrimp over a 20-day period, and juvenile fish are also susceptible. In oysters we have seen some loss of rate of shell deposition in oysters exposed to 5 parts per billion of Aroclor 1254 in the water. (Slide.) We also are looking at the effect of Aroclor 1254 on the estuarine fish. Spot. I thought it might be of interest to you that in tissue distribution studies, the liver contained the highest amount. This is spot exposed In the laboratory by the way. Also, in shrimp, the greatest amount is in the hepatopancreas as opposad to the muscle. I Just show this slide to illustrate again that these are the results of several analyses, if you will notice the graph, the hepatopancreas contains by fsr the greatest amount. We are continuing to work with this material in the laboratory. HONS 068076 16 At this time we ere involved in observing the histopethology of shrimp end fish ehet heve been exposed to Aroclor 1254 in the laboratory. I think that ia about all the data 1 have to present. 1 will be glad to answer any questions. DR. LINDSAY: Are there any questions of Dr. Drake? DR. SENTI: You commented that the fish kill was not actually due to PCB? DR. DUKE: Yes. I think we ell agree that in the Escambia Bay we have an oxygen deficiency problem at certain times of the year. It was at these times of the year that the fish kill occurred. We do not feel that the Aroclor 1254 alone caused the fish kills. We have not done the Interaction experiments necessary to determine *he effect of these levels of PCB in the presence of low oxygen stress. DR. LINDSAY: Are there any further questions? Dr. tforf has come In since we started with EPA and I would like to find out from him if he would like to have any introductory remarks to other speakers from the agency. Dr. Douglas Worf. DR. WORF: Dr. Lindsay has probably told you by now that this meeting was arranged in quite a hurry. We do have a strong contingent here, I think a very good representation of those Individuals who are doing or have done the work and will undoubtedly do the work in this ares that needs to be done. *CNS 06807? >u.tun*. 1*1 nr.iiimurirfcW.,,.-*- 17 This group from EPA ir Or. Hammer, Doug Hammar from our community health environmental group down at the Triangle, the Health Effects group. Just before the meeting he gave me series of reprints of papers chat his group had done and a:*e responsible for. I think he may he\e a few words to say in summarising the work that this group has done and he will make some recommendations for the future. Then we have Dr. Cranmer. 1 did not get a chance to talk to him. I just left a message for him to be here and 1 see that he la here. 1 cannot say exactly what he will have to contribute here, but I will leave that pretty much up to him. Then we have several people who came from our Chamblee Toxicology Laboratory in Georgia. Are that lady and gentleman here? DR. KIMBROUGH: Yes, we are here. DR. WORF: I hop* you will have something to say on this subject. I also called Dr. Norton Nelson. I am glad to see that Dr. Nelson is here. ' Is there anyone I am leaving out from the EPA establishment? DR. LINDSAY: Why don't you go ahead and introduce them as they come up end If somebody else shows up you can take care of It then? DR. WORF: Doug Hammer, will you come up here, end then followed by Dr. Cranmer and then the lady and gentleman from Chamblee. I will leave it up to you for the rest. 1 think Dr. Nelson may be able to give us contributions at any time. i MOMS 068078 18 DR. HAMMER: We have been concerned with PCB and our work it primarily epidemiological. We have studied PCB and other pesticide residue burdens in both urban and rural non-occupationally exposed blacks and vhites living in one South Carolina County. I do have two extra sets of f*ese papers in the back and can have more xeroxed. I Just had no Idea how many people would attend today. We studied a total of 723 people in four residence-race categories, i.c. urban blacks, urban whites, rural blacks and rural whites. As expected, PP'DDT and DDE residues were almost universal. DDD residues were found in 64 percent of the people and Dieldrln was found in 63 percent of the people. PCB residues were found in only 40 percent of the people, with values ranging up to 29 parts per billion. Significant age effects, not always linear were observed for all residues except Dieldrln and PCB. Racial differences were marked for every residue ethnic-residence interactions were also the same except for Dieldrln. There were residence effects for all residues except DDE and Dieldrln, but sex differences only for DDE and DDT. PCB residues were more frequent and higher in whites and in urban residents. Residues were rare in rural blacks, only 4.1 percent of the rural blacks having any PCB residues. Let me give you the mean values for them. For PCBs there were 100 to 150 people in each group. Rural Negroes had an arithmetic moan of 0.3 parts per billion. MGNS 066079 19 Tliis OKain is only 4.3 percent of that population. Urban Negroes had an arithmetic mean of 1.9 parts per billion. Urban whites had an arithmetic mean of 2.3 parts per billion, and rural whites had an arithmetic mean of 3.1 parts per billion. So If you are an epidemiologist, it is not too easy to figure that pattern out. Most of us feel that urban exposure to PCBs would be via polluted air and contaminated water. We have measured PCB In suspended particulates and they are present. Also, we have a contract in progress for the study of PCBs in human balnga and also an industrial use profile of three SAMA'a in South Carolina, looking at certain aquatic and land animals and alao fat and serum from persons having surgery. Summarising, we have in our own small way been concerned about this problem and have been measuring PCB burdens in the general population. Clearly, we did find PCB present. 1 think we all know possible sources of these PCBa. All of these people were asymptomatic and thara Is no raason to,think thay were 111. Nevertheless they are picking up PCB aa they are many other pesticides. Are there any questions? ! MR. BARTHEL: What body fluids or tissues were used? DR. HAMMER: These are in serum. We are also collecting about eight or ten tissues from sutopsied people and we will bs measuring PCB in the liver as well as the fat and serum. MR. MUSSMAN: Have you found any correlation between the fat and serum levels? HONS 068080 20 DR. HAMMER: I do not have the values on the fat levels. The PCB levels in the serun did not correlste very well with the other DDT derlvetlves in serum. MR. MUSSMAN: But In no instance were fst end serum samples selected from the same patient? DR. HAMMER: Right. I've presented completed work. The other work is in progress now and 1 do not have the results and 1 could not get them In two days. DR. FISHBEIN: Do you have a spectrum of the PCBs that are actually involved? DR. HAMMER: Dr. Lamer Frlestor of the South Carolina State Board of Health la doing our ?CB work for us and 1 am truly not an analytical chemist. I know there are probably about 19 compounds that you can measure and he las worked out a fine technique using five "finger prints" and gets about 90 percent of the PCBs present. I would be happy to put you in touch with him because he really understands the method, and 1 am not an expert in it. They are not easy to aiessure. ' MR. BURSE: What techniques did you employ in order to eeperete the PCB from the DDT-like materials? DR. HAMMER: He was using a methanolic calcium hydroxide digestion. This makes it water soluble, removing essentially everything but the PCB. DR. CRAMMER: 1 might speak to you a bit about some of the activities at the Perrine Primate Laboratory in terms of analytical methodology end toxicology of PCBs. HONS 068081 21 Dr. Frank Biros haa utilized the combination of tha mass spectrometer and cha gat chromatograph ro analyze mixtures of these compounds. Basically this concept la a gas chromatographic separation followed by tha selection of a particular component of the PCB mixture for analysis by the mass spectrometer. One can take quantitate compli cated PCB mixtures by selectively examining Individual components, separated by gas chromatography, with the mass spectrometer. There are components of these rather complicated mixtures which are peculiar to or particular formation of PCBs and these are the components of special interest. If you have a mixture of several PCB formulations, which you will often find resulting from general environmental exposure, you may approach representation of body burdtne in the general popula tion of the country. Quantitation of this type of sample would be extremely difficult because of the many components represented in verioue concentrations. If one applies the technique of a gas chromatographic separa tion and the application of the mass spectromenter to the examination of chlorine ratios and fracture patterns an approximation of the relative contribution of the various PCB mixtures can be accomplished. Dr. Enoe, Chief of the Chemistry Branch has been responsible for a program for analyzing human tissues for several years with some considerable success. In cooperation with the Division of Pesticides and Community Studies, he has examined several tissue samples from humans which were extremely high. HONS 068082 22 One technique thet is showing promise in our laboratory ia using capillary columns in the gaa chromatograph prior to the mass spectrometer. This gives extremely good resolution. One does not have quite the problems with the PCB analysis by the mass spectrometer that were experienced with some of the chlori nated hydrocarbon pesticides which decompose on the ges chro matographic columns and on the separators. - We have hed e considerable success when dealing with analysis In the pretence of chlorinated pesticides. If one has a sample with DDE end DDT or several other compounds in the body fat perhaps even from some sort of drug therapy tha problem la immense in terms of trying to ascertain the exact exposure to any particular formulation, if no aelactive criteria la applied. .towever, with PCB analysis Just as with other types of analysis there is no substitute for good clean up procedures. Of course, I am not saying it la going to be easy. You can tie up a gaa chromatograph and mass spectrometer combination for two or three days analyzing one complex sample if you want to do it accurately. However, et the Perrine Primate Laboratory we are now including analysis for PCBs In our pesticides residue chemists' training course as pert of the standard procedures because these compounds are showing up in so many human tissues in the monitoring program. 1 would like to aay just a few vord6 about the experimental animal work that we ere doing on the interactions of PCBs on the toxicitics of certain pesticides. HONS 060003 Mtsta 23 One- case that you may lie interested In Is s vitamin C-deficicnt guinea pig. You get a fourfold decrease in the I.O5Q of 1260 in ascorbutic guinea plga. ' A diet of 50 part* per milllo'i of 1260 in the diet of a rat, decreases the fat storage of lindane by 75 probably through - microsomal ensyme accumulation but slightly Increases the storage of p,p'-DDT. This is interesting since here we have two pesticides, both chlolnated hydorcarbona, being effected in opposite directions in terms of their storage. The toxicity of the organophosphate insecticide parathion la altered in the vitamin-deficient animal when you pretreat with 50 ppm 1260. You change the ratio of the meta bolites of parathion that are formed. Parathion, is metabolised by two major routes. One is the direct detoxification and formation \ of diethylthiophosphate and p-nitro phenol. The second pathway first oxidises parathion to peraoxon which is then further metabolise to diethyl phosphate end p-nltrophenol. Then you break that up to diethyl phoephete and other materials. With pre-treatment with PCBs you get an Increase in the parathion to peraoxon metabolism rate. One might at first expect if you were getting more peraoxon that you should produce a more toxic situation. The rate of cholinesterase inhibition is increased in animals pretrested with 1260, due to the more rapid conversion to paraoxon but the total depression of cholinesterase is les^.since the biological half life is shorted due to the simultaneous increase of the direct detoxification pathway. AOIlS 068084 In sunanary, I would Ilka to eap'.iasixe that PCB have many interesting effects, on the metabolism ari toxlcities of pesticides and other compounds and one should avoid generalizations about the toxic effects which have yet to be described. Thank you. DR. HAMMER: I just wanted to mention some work that Is being done not supported by us down In Charleston, South Carolina, where PCB at levels of 0.001 to 0.1 parts per million has been concentrated up to 200,000 times in coll. DR. CRAMMER: That la Interesting. X think the amounts of DDT required for no effect on your liver microsomal enzymes are approximately the seme in the Immature rat. I think you can draw tome correlation. DR. WORE: I think next ve will have Dr. Kimbrough and next her associate, Mr. Burse. Dr. Kimbrough is from our Toxicology Laboratory in Chsmblee, Csorgis. ' DR. KIMBROUGH: Thank you very much. We have studied the toxicity of 2 PCBs, Aroclor 1254 and Aro- clor 1260 in the Sherman strain rat. Let me apeek first of all about Aroclor 1254. The acute oral LD^q ln adult rats is greatar than 4 grams per kilogram. We also undertook a subacute feeding study in both mala and female rats which Included a reproduction study. 1 will just give you *<xe of the results that we have now and if there are any questions 1 do have some tables that I cannot present but I can look up some of the facts. MONS 068005 25 We found Chat feeding 500 parts per million to both male and female rats over a period of about 240 days lowered the hemo globin and the hematocrit. These animals also showed less weight gain. As far as the reproduction study was concerned, a definite effect on reproduction was produced at 100 parts per million. We did the first breeding after 76 days on the treated diets and we noticed this effect then. There were less offspring. The offspring at weaning were smaller and the survival was decreased. We did study a lower dose, 20 ppm, and noticed no definite effect on reproduction except that the number of animals born was slightly lower. When we did autopsies on these anlsials we found that everything from 100 ppm on up showed an Increase in the liver weights. Most of the other organs were more or less normal. There were some exceptions which 1 will mention later. We also found that some animals had porphyria. We found that in the male rats fed Aroclor 1254 it was produced in some animals at a dietary level of 100 ppm (approximately 5 mg/kg per day). There was none at 20 ppm. In the females we found fluroescence of the urine as well aa the plasma at 20 ppm. We are going to look into this more. Sometimes neither plasma nor urine fluoresce but a pigment will be present in the liver -- we have also had some rats where we found fluroescence of the teeth and other organs. It doesn't occur in all the animals. It occurs more in females than in males. HONS 068086 ,ntfcri I Till Mil 26 We also performed autopsies on the offspring. We found an increase in liver weight in the F2. generation of the- weanlings at a dietary level of 20 ppm. . Ue also gave some rats several, dosage levels of Aroclor 12S4 during pregnancy. The dose that caused an effect was 50 mg/kg/day given during the 7th to the 15th day of gestation. Giving the material dermally at the dosage level of 50 mg/kg/day for 30 days an Increase in the weight of the livers of the exposed animals was observed. I would tike to give the toxicity data on the Aroclor 1260 now. In some of the animals that I have mentioned Mr. Burse has determined PCBs In various tissues and he will present his findings following this report. The Aroclor 1260 seems to be leas toxic. We found that the oral LD$q was more than 10 grams. At a level of 500 ppm the hemoglobin was affected. The body weight was affected in the animals that were fed on a diet ot 500 or 1000 ppm of Aroclor 1260. The livers were Increased in size at autopsy. The livers were larger and heavier from the dietary level of 100 ppm on up in male rats. In the females in thla feeding study the liver weights were not significantly Increased at any of the dietary levels that were tested. The reproduction, with 1254, was definitely affected at 100 ppm. With 1260 it was not affected at 100 ppm but was affected at 500 ppm if the Aroclor 1260 waa fed over a period for 76 days. We again found fluorescence in the urine in some animals which Indicates porphyria. We found It in one of 10 males at 100 ppm MCNS 06809? T ,-------- 27 In the urine and in Clva of Can females at 100 ppm. W found nona at 20 ppm in aithar aax. But vith tha 1254 wa did find it at 20 ppm in aome femaia rata. Wa alao doaad eras anlmala vith varioua dosage lavala of Aroelor 1260 dally during tha 7th to tha 15th day of pragnancy. Tha doaaga laval that gave an affaet vaa 100 mg/kg/day during that parlod. Tha numbar of the offapring born and thaI \ ^----------------------------- --------------------------- [I \ aurvlval of tha offapring vaa raducad. v\ "Tfia findings that vara made vhan tha llvar vaa atudlad can ba divided into diffarant parta. Ona la that tha llvar calla ara enlarged in tha anlmala that have received Aroelor over a parlod of time. Thia oecura with 1260 aa vail aa with 1254. In addition accumulation of fat la found in tha llvara. Soma of tha changaa that have bean daacrlbad with chlorinated hydrocarbona auch aa tha inclualona within tha llvar calla and tha so-called marglnatlon can alao ba observed. At tha higher doaaga lavala (1/10 males and 6/10 females at 100 ppm Aroelor 1254 in tha diet for about 8 months, 1/10 female rata at 100 ppm Aroelor 1260 in tha diet for 8 months, none of tha males, nona at 500 ppm, but several at 1000 ppm) a vary pronounced change la found which haa bean termed adenoflbroals. There ara diffarant opinions on vhat adenoflbroals represents. It consists of fibrosis in tha llvara concomittant vith a proliferation of calls which by aqme ara considered to represent proliferated bile ducts. Others feel that they represent undifferentiated hepatocytes which proliferate when destruction of dlffaxentlated hepatocytes occurs. . In many of tha livers 1 also observed a brown plpnent which 1 assume is porphyrin. We did find fluorescence in these livers st autopsy. M0MS 066088 28 Occasionally other organs shoved changes. In some animals hyperplasia of the thyroid vas observed. The incidence of bladder cancer In our rats oust be vary iov, but 1 do not know uhat the aetusl Incidence is. The animals are random bred. I have vorked at the Toxicology Laboratory since 1962 and 1 have until now never seen a rat with bladder cancer, but thla doesn't swan that they could not occur apontaneouely. I did obaerve cvo bladder cancers in animals that vers fad 100 ppm of the Aroclor 1260. The stgnlfl* canee of this finding is doubtful at praaant. However, it should be Investigated whether PCBa have any carcinogenic potentials. Now, could 1 have the slides, pieaaeT This first one shows the liver of an animal that hes racalvad Aroclor 1254 over a period of 8 months. You ean tea the enlargement of the liver cells. You also sea quite a number of mitotic figures, flare la an inclusion in the cytoplasm which resembles inclualons observed in the cytoplasm when rats have been given high does# of chlorinated hydrocarbons. The PCBs seem to cause similar changes In the liver. In the next tilde you see e normal liver of a control animal. The next slide shows another stain. The previous two slides were hematoxylin aosln stains and this is a PAS stain. This shows the so-called "duct formations" which Is psrt of the adenofibrosls. They are lined by hepatocytes which are reduced in slse. The next slide, shows a very good illustration of the adenofibrosls. Note epithelial cells that line duct formations which sometimes contain s cellular debris. Increased fibrosis which is shown in this area le also seen. MONS 068089 29 Tha naxt slid* 1* an Illustration of baginning fibrosis. Some haps :ocytes hsva dark nuclal and soma of tha "duct formations' which contain a mucinous material are also saan. Tha next slide illustrates again the adenofibrosia which sometimes can form nodules in tha liver. It has happened that they have been called tumors but they are not. It is a reactive prolifer ation that can occur in the liver when liver cells are deetroyed. Tha next slide shows a fat stain which demonstrates the amount of fat found In these livers. I have done a little work with the electronmlcroacope. We are planning to do some more work with it. Are there any questions? MR. BURSE: Mr. Chairman and ladies and gentlemen, l am Vlrlyn Burse from the Atlanta Toxicology Laboratory, Atlanta, Georgia. The chemistry section of the Atlanta Toxicology Laboratory has been analysing blood, tissues and some excreta for residue levels of PCB derived materials with emphasis on Aroclor 1254 and 1260 using gas chromatography in addition to other systems. We have evaluated three approaches to the separation of PCB frosi DDT-like materials, namely the TLC approach, using silica gel as an adsorbent, the Reynolds procedure, using florosil ad an adsorbent and the Armour Burke procedure. See Appendix 1 for the complete manuscript. In the mass spectrometer work that dealt with tissues our work paralleled the mass spectrometer work that Dr. Bagley reported concerning Aroclor materials in bald aaglea. HONS 068090 A*1' lilli^ilwi^W'iteiif.rti.l imfcrilii in iiiilMirti ir I ,-nUm,- eww- , ,,,, 30 ; '' i '! I '' ' ; ' :, 'l ; Thera la something Id tha urine of Experiment C (Appendix 1) that I think la vorth mentioning. We combined aa lac ted a ampler from Che urine atudy and examined them by man a electrometer and found tha ` uaual chlorinated clutter. We found clusters at 254 matt unite, at 288, at 324 and at 358. There was an leotoplc clutter which waa Indicative of four chlorines that we found at 304. Initially we were trying to figure out what could possibly give a molecular weight of 304 and have an isotopic cluster which waa indicative of four chlorines. We know that It cannot be polychlorinated biphenyl. About two weeks after this work was done I waa looking through Food, Cosmetics, and Toxicology and found a paper by Dr. Voa from tha Netherlands. This work was a follow-up on some previous work that he had done with chicks published In Toxicology and Applied Pharmacology. Ha was looking at the Aroclor 1260, the German product, the French product and tha American product. He found discrepancies in the effects of the dosege levels of these three compounds. The two forelgi products fell mors in line together and the Monsanto product waa quite out of line, with the total effect of the Monsanto product being just signs of porphyria. Ha assumad there was something In the two foreljpi products chat resulted In the anomalies he was seeing. After he fractionated these two foreign products on florlsll he was able to find the tetrachlorodlbenzofuran and the pentachlorodlbenzofuran as well as some chlorinated napthalenea. ;i MOMS 068091 31 The 304 doe* fell In line with the tetrachlorodlbentofuran. However, we have not been able to confirm one way or the other that thla la 304. I have taken the Honaanto product, Aroclor 1254, and fractionated It from florlall, looked at the elution pattern* by conductometric detection, and eluted until all the PCB pattern vaa (tone but have yet to look at it on the mata spectrometer. f This la work that la pending. We have alao done aome work relating to reproduction atudleti with Aroclor 1254 and 1260.(Appendix 11) We plan to continue effort* to laolate conatltuenta of Aroclor 1254 In the atandard aa well aa Isolation of conatltuenta of Aroclor In body fluid* to determine what 1* responsible for the effects resulting from acute and chronic exposure to Aroclor. Additional work will be done to determine steady state values for Aroclor at a high level aa well as low. Two additional proceduraa using TLC will also be evaluated for separating PCB from DOT-like material. One Involves chemical degradation of DDT-llke materials and the other Involves triple development on TLC using Kleselguhr which Is a method that Dr. Vos from the Netherlands has published In the Bulletin of Environmental Contamination and Toxi cology. DR. WORF: Thank you very much. 1 think Dr. Lindsay has suggested we have a coffee break. Before we do thla 1 would like to thank the EPA people who made the presentation here on very short notice. 1 think thla la Rood hard data. HONS 068092 There are some gaps in the EPA program that we could not Include. We do have a strong program In monitoring this type of a chemical In the environment, both In the water and In the air 32 and in tha tell and In tiaaue. Tha ttaaua part vaa pretty wall daaerlbad hara today. ' brTpyindla of our Watar Hyglana Lab unfortunataly la not hara an<> haa had conaidarablc experience In monitoring and developing tachnlquaa and templing techniques and inatnaaentatlon for determining PCBa in water. Vlth thla Z think va will taka a coffaa braak. DR. LZMDSAY: I would Ilka to auggaat that, at a poaalbla way of gattlng toot of thla tachnlcal and datallad Information wore completely disseminated, parhapa wa can ataaaarlaa from tha pcdlia and than. If lta all right with tha paopla who ara providing It, wa con amplify thla for tha record. Vo will try to gat dlatrlbutlon to everybody that la hare without Jeopardlclng publication proapacta for It later. Thla la atrletly an Interagency type of exchange and 1 don't think thla will constitute jeopardy for tha later publication or acceptance by aowe critical edueatora. We will taka a abort coffaa braak and be back hare by quarter of eleven. . (Short reeeee.) DR. LINDSAY: Aa Z indicated earlier, there la no agenda, tte are trying to play It by ear ao 1 will reiterate what tha "no agenda" la. Wa atlll have aavaral people to hear from in the Food and Drug Administration and there la a gentleman from the Department of Agriculture that we would like to hear from. Then we want to hear from aone of the people from outalde the Government who are working In thla field HONS 068093 ^MiaLJUflri'klllWB lixutiiMBMiiiiatj. LlifiiBi 33 of PCB research who can review some of chelr work, particularly as they relate to the problems of the regulatory agencies. They may have other areas that would be interesting, but we are particularly concerned about how their work fits Into some of the problems that we have. Over on the chairs against the wall you will see two or three piles of Xeroxed papers. The larger piles consist of what we call "status reports." Dr. Herman Krayblll Is primarily responsible for getting these together in the Food and Drug Admin istration. Ue don't apologise for them but they are out of date. The June 1970 and the supplement of December 1970 are there but they are a little bit old now, the way PCBs have been moving. We don't have enough to go around. He would appreciate it very much if each group of people would noc take copies for everybody but get only what you need. I would like Mr. Duggan to give a situation report with regard to the Food end Drug Administration. Just before we go into the activities of the Bureau of Veterinary Medicine I would like to aek Dr. Sent! to Introduce a man he discovered wee here who could lead into some of the animal feed problems. MR. DUGGAN: It Is nice to see so many familiar faces. We had a "meeting on PCBs about a year ago and a lot of you were at those meetings where we were going to talk about emerging problems. Since that meeting we have had problems emerge more than once. HONS 06*094 'n"Tir*rwrii*M - -u 34 Now we are right in the middle of one of the emergencies. 1 think 1 will start off by giving the FDA regulatory policy on PCS* in foods. It is a very simple one: we do not approve of any foods containing PCBs, nor do we condone any practices which result in any levels of PCB residues in foods. While that may be our policy, until there are some legally sanctioned uses. We have been forced to compromise that policy to the extent that we do not object to the marketing of certain specific lots of food that might contain some low levels of PCBs. 1 do want to stress the difference between approving and not objecting to. I think this is the key. In tills particular Instance of poultry we have advised the Department of Agriculture that we will not object to the marketing of poultry that contains 5 parts per million in the edible portion or 5 parts par million in the separate fet. That means chat any time the fat la separated out during slaughter or processing as a finite substance to be used In other food products the 5 parts par million guideline will apply. In terms of animal feeds we have advised them thst the use of feed Ingredients contained in detectable levels of polychlori nated biphanyla for food produced in animals is neither approved nor condoned by the FDA. Such adulterated feeds can be used for animals not uded for food purposes provided It1 la not toxic to those animals, or for non-food purposes such as fertilisers or industrial chemicals. We have had this problem face us a number of tines over the past three of four years. We have had a couple of instances where we were pressed for guidelines by the states which had discovered PCB 068C95 mjl, 35 residues it. milk. We gave them s guideline of .2 parts per million to deal with the particular situation. The preliminary thrust of our Interest in those Instances was to discover how the PCBs were getting into the milk and how it could le prevented. In one instance I think it was pretty well established that the silos had been painted with a paint containing PCB. The states did take action and they kept that milk off the market. In another case 1 believe It was pretty well established that one of the power companies had disposed of excess transformer oil in spraying thalr rights of way and dairy herds had been grased on those rights of way. More recently we had had this problem of poultry in the State of New York. Through the activities of the state and the Department of Agriculture the major poultry Industry in the State of New York I think properly contained the problem of marketing PCB contaminated poultry end eggs. 1 do not believe we ever finally nailed down the source of that contmlnatlon, though there was some indication that it might have been due to the practice of grinding up bakery products without taking them out of the packages and throwing the whole package Into the animal feed system. ' This brings us down to the present problem. MQNS 060096 Friday afternoon about 5:15 on the 16th of July the Monsanto Chemical Company celled and said they Just wantsd to toll me that there was an awful lot of fish meal in ths State of North Carolina that was contaminated with PCBs and that the company 36 involved was the East Coast Terminal. Vith fish meal being used at an animal feed end with the accumulative effects Into the fat of animals, we thought perhaps we had better get the boys out again on Saturday and Sunday to investigate the problem because at that time it was only a rumor. You know, you get a lot of misinformation over the telephone. By Monday morning the Atlanta Regional Office had visited the terminal. They found that the fish meal that was ready for shipment was contaminated. It contained anywhere from 12 to 20-some-odd parts per million PCBs. You might wonder what PCBs were doing in a fish meal plant to begin with. Fish meal is often contaminated with salmonella. We object to the use of salmonella-contaminated fish meal In animal feeds. So the companies have adopted a policy of pasturlsing the fish meal. In this case it is done by passing the fish meal through a system with the heat exchange fluid in the hollow screw. It seeme that fish meal has a facility for eating holes in these screws. After some investigation wa found that this had probably started occurring about the end of April end they had been fixing the screw off and on during the process. Later on it developed they had refilled or ueed about 5,000 pounds of aroclors In the month of June. We found that they had shipped about 16,000 tons from the end of April until the 16th of July. We dfcd request erabargos by the state organisation and began to list shipments. The manager of the plant did not seem to have a whole lot of authority. This is why Monsanto finally called ua up. They* *0NS 060097 37 had known about thla for several days. They had tried to sell the company some different heat exchange fluids. The firm did not pay a whole lot of attention to them not realising the aignificance of the problem. The actual operation and direction and policy for this particular plant is vested In the South Pacific Protein Company headquartered in Darien, Connecticut. As Dr. Stein has mentioned to you, the Department of Agriculture learned of this on Monday, about the same time that we had gotten our results in, and they were asking for guidelines on the poultry that might be contaminated. Ve had had a guideline for the New York incident, but we had told them it was not applicable to any other situation. This then swant that we had to get our scientists, our Bureau of Foods and Bureau of Veterinary Medicine, involved to take another look and see what guidelines we could use in this particular case. The manager of the South Pacific Protein Company came down to talk with us on Tues4ay. He imediately saw the gravity of the problem, particularly in light of the fact that this la used st about two percent in poultry feeds, which means that there could be well over half a million tons of contaminated poultry feed in the system. He stated that he would have to go back and discuss what he was going to do with the plant manager, who happened to be in Peru at the time. Apparently this is an integrated operation too, and these firms are owned by Peruvian Interests. They sre not, as far as MOMS 068098 .11 aiiwT' - iii nif-i > iMuTiatiii 38 vc can deternlne, a part of the Peruvian Government. At any rate, early Wednesday morning he edviaed u> that * he had issued telephone Instructions to all of hia consignees asking them to return all unused fish meal to the North Carolina plant and that they were to ask their customers to return all of the fish meal to the North Carolina plant. This recall is going satisfactorily. We are now engaged in looking at the eggs that might he produced from this. We are also looking to determine vhat happended to the eggs thst did not hatch, whether they got mixed up Into the Incubator reject rack or if they went for industrial purposes as they are supposed to go. This Is pretty much where we stand at this particular sMeient. I think one thing we must recognise here is that we are not dealing with quite the same problem ae we are dealing with in the pesticide area. There have not been the widespread direct uses of PCBs on food crops or in food establishments. This Is s fact. Unfortunately it has fanned out into a major problem. We are not yet at a point In cur toxicology information where we cen establish a guideline for ell foods. I think we ere going to have to continue to deal with these other circumstances Involved in each case. It is not an entirely satisfactory systam, but until we have a better system I think we are stuck with this one. I think that is about all 1 have. I will be glad to try to answer any questions anyone might have. MGN5 06609$ MR. BARTHEL: What levels did you find In eggs? Mr. DUGGAN: tfe have not put that together yet. tfe expect to have a fix on that about the latter part of the week In speaking of this, as you know, PCBa will be detected In the ordinary pesticide multi-residue method. Since our meeting last year we have been very much aware of this and have been looking at the chromatograms during the routine surveillance of our food for PCB residues. 1 have enough confidence In the ability of our field laboratories to believe that if there had been any substantial aoxnmts or abnormal amounts, let us say, approaching detectable and measurable levels of PCBs in egg saaq>les generally we would have heard about.lt long before now. We do not believe there should be any detectable residues in eggs. This works out, 1 understand, to about a .5 parts per million guideline. DR. BURGER: Just to make sure 1 understand, there Is now an administrative guideline for PCBs In animal feed, in milk and in fish; is that right? MR. DUGGAN: No. DR. BURGER: X am sorry. MR. DUGGAN: We have no guideline. There should be no detectable levels of PCBs In animal feeds. There is a guideline for milk. There is a guideline for fish. There is a guideline for poultry. Now, these are interim guidelines. They were set to deal with specific Instances. If Joe Stein calls me up next week HONS 066100 40 and call* m* h* haa a problem with PCBs In turkeys In California, for example, then ve are going Co geC Che circumstances surrounding that particular Instance and then ve will look at lc in tense of the new toxicology ve might have, how It could have been prevented, and then deal with it on that basis. In other words, these guidelines that wa heve talked about here today are not across-the-board. DR. BURGER: Is there a systematic scan for PCBs In fish at this point? HR. DUGGAN: Yes, they will be picked up In the multlresldua methods that ve consaonly use for pesticide residues. DR. BURGER: Although you say they are not necessarily specifically for PCBs? MR. DUGGAN: The fingerprint for PCBs Is quite Identifiable and recognizable. I think there may be someone from the Bureeu of Foods who can talk more specifically to that point. DR. BURCER: A final question. Did 1 understand you to allude to an lnduatrial uae of eggs? HR. DUCCAN: Yes. DR. BURGER: What is that? MR. DUCCAN: I think they use eggs In the manufacture of tanning, preparations for tanning leather. This Is one use. I suspect there are other uses as well. DR. BURGER: Thank you. DR. LINDSAY: Dr. Sentl, would you introduce our next speaker. *0NS 068101 41 DR. SENTI: We have Dr. Fries here of our Animal Science Research r-lvision who has had soma experience with the feeding of PCBe to livestock and he .will give a brief summary of that work. DR. FRIES: 1 will cover this very briefly. Last lumcr 1 was called in to give advice to a farmer who had been taken off the market because of excess DDT in milk. I decided to use this as a field study. It was a short time thereafter that 1 picked up the strange peaks which we identified later as PCBs. We were certain of the Identification because the Baltimore FDA laboratory had found PCB in the milk of this farm previously. The souree of PCB was silo paint. By coincidence the cows had been taken off the contaminated silage st about tha same time we removed them from the source of the DDT contamination. We were able to follow the levels of both contaminant! for a alx month pariod. Wa sampled the cows individually every three weeks through the decontamination period. When e cow lt.renK>ved from PCB contamination, there le a SO percent drop in the level of the milk within about the first three weeks. This is very similar to DDE. Than there Is a alow rate of decontamination as the PCB is removed from body fat. This rate la about 1.3 percent per day. This le identical to the DDE. In fact, any grouping of cows you take - individual cows varied very little but on any average group of cows the two c'ompounds behaved identically. That pretty well eurnnarlees the field work. We are now feeding Aroclor 1254 to cows et Beltsville to establish relationships between the input end excretion In the milk. HONS 068102 Jtmm.., 42 Arochlor 1234 has been used in silo paints and is probably the biggest PCI1 problem facing the dairy industry. 1 think this problem is possibly bigger than has been suspected. I think there are quite a few of these silos around. I might also mention that Dr. Bitman's group at Beltsvllle is doing work on PCB with rata and quail. They are studying effects on egg shell thickness in quail, vitamin A storage, and effects on the liver ensymes. I am not prepared to talk about their results. 1 do have a mimeographed summary of this field study. If someone la Interested in the details they could write me for a copy. Are there any queatlons? DR. HOOPXNGARNER: X was curious if activated charcoal would help reduce this quicker? SR. FRIES: Mo. In fact, that vaa part of the study. I have a disagreement on this subject with one of your colleagues at Michigan Stata. That la part of the study and it Is Included in the mimeograph. They had activated charcoal on the farm before 1 became involved. Ue fed activated charcoal in combination with phcnobarbltal as well as phenobarbltal alone. Neither treatment had an effect on the rate of decontamination. I would suspect that if somebody had contaminated silage and fed activated charcoal with it, they would reduce the PCB level in milk by at least 50 percent or more. . 1 have looked at a number of other farms having these silos. in general it Is a borderline situation. Some of the tima MGNS 068103 in ! 43 during the silage feeding period the milk level Is under che guideline end sometimes it Is just slipping up over it. The levels ere reesonebly compersble to the levels thet hsve been reported In Ohio where they hsve been teking some dairymen off the market. DR. STEIN: In running your field survey did you do eny biopsies on those milk cows? DR. FRIES: I didn't do biopsies on the field survey. I an doing biopsies on the study 1 have underway at Beltsvllle. DR. LINDSAY: Thank you. Dr. Fries. Dr. Mercer, ere you going to speak for the Bureau of Veterinary Medicine? Will you tell us where you stand with it now? DR. MERCER: As with moat programs which have a very loose agenda, if you are able to sit back long enough, whatever you have to say will be said, so I don't think this will take very long. I was not necessarily prepared to give the position of BVM on the PCB problem. 1 was more or less prepared to talk about lnavallable toxicity information relating to domestic animals. Two of the major concerns of BVM, of course, are, one, the safety aspects of PCB to food producing animals, as well as other animals that might be consuming PCBs and a second major factor that gets s greet deal of attention Is the tissue residue aspects In the food producing animal, as might be obtained through the feed sources. Fortunately you have just heard che data from Dr. Fries that probably gives us es much information as Is available on dairy cows. I think it is well established that for a long lime wc may have been MOMS 060104 44 measuring PCBs in milk and calling them DDT or other chlorinated hydrocarbonr. I am going to briefly bring ua up to date on the information that wc do lave available on the toxicity of PCBs in domestic animals and poultry. There are a couple of papers that give a very good xeviev of vhat is known about the toxicity of FCBs. Dr. Lindsay referred to the status report that Bureau of Foods * FDA, has prepared, end whleh Is available, which covers the literature up until the letter part of 1970. There la no point in going Into a detailed dlscueeion of this published information. A recent review article by Peapall and Linear, the only one 1 am aware of, does review the toxicity of the PCBs and was published in 1970. Both the FDA status report and the Peapall article will serve to give a very good background with regard to what la known about PCBs. There have been some toxicity studies conducted in poultry. 1 believe the classic work was done by McCone et. al. 1962. I trill briefly give you a summary of their findings. McCune fed chickens four-levels of PCB; 100, 200, 400, and 800 parts per million aa a component part of the diet. The chickens at the 100 parts per million level shoved no effect on the liver. They only erfowed a alight fluid accumulation In the pericardium. The bird with the 200 parts per million level showed no liver effects. They did show a more extensive hydroperi- cardlisn. As they went up the scale, the 400 and 300 parts per million in diets they began to observe more gross toxic effects on other organs as well ss quite extensive hydropericardium. *10NS 060105 45 There wee eleo some work reported by De Nos end Kolman, 1970 on chickens receiving 200 and 400 parts per million for tvo weeks with a 60 percent chlorinated PCB. They found some effects at both of these levels; kidney effects at the 200 parts per million level were extensive with hemorrhage and enlirgement of kidneys occurring at the 400 parts per million level. They also Saw hydropericardium.. They found some enlargement of organs such as adrenals and spleen. The pancreas was also effected. Beyond this work in chickens, the Information becomes very scanty. We will be hearing a report from Dr. Harris of North Carolina, who le currently Involved in some toxicity studies with chickens, and I believe he will be reporting on what he is finding. This Information will be most pertinent at this particular time. A number of studies have been conducted on wild life and there have been e few toxicity studies done on ring doves where they have noticed some effects of PCBs. However, none of these studies really give us much In terms of a dose-effect correlation. This is the type of correlation that we need most in order to start chinking about regulatory guidelines. Vhat kind of a tolerated dose can we afford to have. Dose effect correlation data is Just not available. When you get beyond poultry, and gat into the swine or calves or sheep or any of the other domestic animals with which we are concerned regarding food production capabilities, toxicity and residue data gets extremely scarce. 1 do not know of any information on these other species et MQNS 066106 this point. If there it any current research going on In these aress I would be most happy to learn about It. It is certainly not in the literature. The other aspeet that we need to have more Information on is the tissue distribution and excretion pattern of PCBs. The best article that ve can refer to in terms of published information on the metabolism of PCBs is an article that Grant et. al. published in which they d!4 a metabolism study on rats. Again we run Into this hairy question of extrapolation from rats to other domestic animals. Thay did report some interesting literature, including evidence that PCBs vara being found In human milk. This information has bean substantiated In dairy cattle, where measurable levels did occur In milk. But basically I think tha Grant work confirms some previous data that was given to ua by EPA people this morning and that la that the primary organ of concentration In the rata was the fatty tissue. If you compare on e relative basis fat to serum, assuming the serlum has a value of 1, the data, in general, that Grant published showed something like 508 parts per million in fat compared to 1 part in blood. Tha next major order of concentration was the liver, 59 parts per million coopered to 1 In blood. The brain tissue, being the next in the sequenclal order of concentration, then the kidney, apleen, heart, testes and no muscle tissue showed measurable residues. * , MONS 068107 V i |J 111 1- >lf| - 47 i am not aware of any dose concentration correlation studies in the muscle tissue of birds or any other animal, as far as that Is concerned. 1 think this is an area that we must become Increasingly concerned with if ve expect to have any impact on the regulatory aspects of PCBs. There is no further toxicity or residue data ve can talk about in domestic animals. We would be happy to entertain any questions you may have. DR. GORDON: In your mind doea the Bureau of Veterinary Medicine think that the outbreak of hydropericerdlura that occurred in early 60's, Is that associated only with PCBs or in the Bureau's mind Is that associated with other factors? That vea a major problem in the poultry industry at that time. DR. MERCER: 1 think in answer to your question that ve will feel much more comfortable at some of the data that is currently under way and the results become more available to us. Again, 1 refer to the work that is going on in North Carolina. I think ve will have some confirmation as to whether or not this vaa a sola effect of PCB. At this point all ve have to go on Is reported literature and you have to assume that this is what the major effect vea. DR. FLICK: I vss wondering if Dr. Gordon's question ves pertaining to the chick edema disease which occurred In the late SO*a end early 60's. This disease was not due to polychlorinated biphenyls. The evidence thus far Indicates that these are polychlorinated dlbenzoparadloxlnt and Indeed are quite toxic. The polychlorinated biphenyls ere toxic and produce syndrome which we might call dloxinosls. However, HONS 068108 malm 48 the levels of intake are much higher, several hundred fold to vhat ve observed with the polychlorinated dib<nzoparadloxlns. DR. KIMBROUGH: I would like to add something to this. The work by Vos and his coworkers has bean cited several times. These authors pointed out that they fourd hydropericardlum which Is the chlckedema disease in the chickens that they led with PCBs They found chlorinated dlbensofurans as a contaminant in the European FCBs that they studied. They suggested that chlckedema could also be produced by the chlorinated dlbensofurana. DR. MERCER: Thank you for your contribution. That plus the diamines gives us a real problem. Are there any other questions? If not, thank you. DR. LINDSAY: Thank you. Dr. Mercar. Dr. Kolbye, can you tell us s little bit about the Bureau of Foods? DR. KOLBYE: I will comment briefly and then act as M. C. for some of the other staff. I voulk like Mr. Les Ramsey If we can gat the projector to work to put on the screen some of the residue data to give you e quick idee of what we have found in certain food sampling. Then 1 would like to esk Mr. Cook if he has anyting further to add to the chemistry and then ask Or. Kraybill to tell us what are some of the gaps in our eoxicologlcal research. Las, why don*t you come up end just give a runthrough on these? HONS 068109 I* 'i bni iaiiASittln~ifaNilW.i -...... '9 MR. RAMSEY: The film looked as If It would not be visible to most of you. Perhaps I can summarise it, although trying to summarise residue data orally is not very satisfactory. Vhat 1 want to do is to indicate what our residue findings for PCBs have been in the past year, the period from July 1, 1970 to June 30, 1971. We have looked for PCBe in all the samples that we screened for pesticide residues. In our pesticide surveillance and enforcement program every sample that is analysed there is also screened at the earns time by the multi-residue method for PCBs. In this program in the past year ve looked at 570 samples of fish. 315 of those smnples were positive for PCB. The overall average is of the order of 2-to-3 parts per million, m other words, the fish that we analysed, at least, do not run as high in PCB as the fish do in total DDT, that is, DDT plus DDE plus DDD. We have analysed 1,193 samples of cheese and found 81 positive. The highest level was 1 part per million, and the average about 3/10ths of a part per million. We have screened 805 samples of milk. Of those, 60 were positive and were identified with the contamination Incidents that you have already had described for you in the West Virginia area, in the State of Ohio, and I believe ii' the State of Kentucky and perhaps some of the other states of our Atlanta Region. Some of those samples ran as high as 28 parts per million PCB in the fat in this West Virginia Incident that Mr. Duggan described, HONS 068110 `nr'M.t.'i'i. m r>*> ............. -rr^M 50 where the trmsformer fluid wee apparently used as a solvent for herbicides u ;ed to control weeds on the right-af-vay there. Let me say that the samples that have been found positive In milk have been looked at and the situation investigated. Usually it has been due to some accident such as the feeding that was discussed with regard to the silage in the silos painted with paint containing PCB or arlaing from the pasturing of land that had PCBs sprayed on it for one reason or another. 317 eae^les of ahell egge were looked at. Eighteen of those were positive for PCB. The highest level found was 5/10ths of a part per million. The average, of course, la much lower. We have found traces of PCB in the by-product from two potato~proccsslng plants. One was in the Denver District and the other in the Seattle District. The waste coming from those plants shoved traces of PCB. And so fsr as I know ve have not yet been able to identify the cause of the PCB In the waste. We have looked at a number of oyster*. And, incidentally, oysters, by and large, do not have high levels of PCB, at least the ones ve have looked at. The total shown here In this table is 12, but 1 believe wc have looked at 20 others in the Galveston Bay area. And, again, the highest found was about l/10th of a part per million in the oysters. We have looked at some miscellaneous foods. One sample of cat food showed 6 parts per million of PCB. MCNS 066111 51 A sample of crab neat shoved J/lOths of a part per million. We even analysed the coating that was used on one of these silos involved in the milk contamination, and the coating contained 11 parts p**r million. We looked at a sample of wheat, and it had 3/10tha of a part par million, while one of straw had 3/10ths also. These are a limited number of samples, from which 1 think it la impossible to draw any firm and reliable conclusions. We have also, of course, begun to look for PCB in our total-diet studies. In the fiscal year 1970, out of our 30 market baskets, we found one composite of dairy products positive for PCB. It contained 0.0S parts per million. In three market baskets we found the meat, fish, and poultry to coi.taln PCB. Again, the highest level was about a tenth of a.part per million. We also found one sugar composite positive, which Includes i candy, incidentally. And we think probably the PCB was in the candy, perhaps, in a wrapper or from some other source. The level, again, was very low, 0.08 parts per million. In 1971, with 19 market baskets reported thus far, the frequency has gone up in the esse of the meat, fish, and poultry composites. We have had 11 positives, ranging again to 0.13 of a part par million. Also, we have found two Instances where the cereal products composite contained PCB. And In one instance this was traced back HOMS 066112 to Che shredded wheat In Chet composite, which was picking up PCB from the container Chet bed been fabricated from waste paper. More recently we have looked at some waste paper and have gotten some information from the paper Industry. And it appears that waste paper generally has PCB in it ranging up to 700 parts per million. The so-called carbonless carbon paper runs very high in PCB. In other words, in summary, we have analysed about 9,000 samples of food in the past year for PCB, and about 500 of chose were positive. DR. K0LBYE: Are there any quaatlona directed to Hr. Ramsey? &kis. 1 might add one note. Lea, 1 am not sure you mentioned So far we heve not reported the residue of PCB in fresh fruits and vegetables. MR. RAMSEY: I should have said that we have not found it. DR. BOOTH: I would like to aak a question regarding the PCB levela in shredded wheat and also in some of the other plant materials that were mentioned. You did mention that It probably came from the wrapper in the ease of shredded wheat. I was wondering if plant# can taka up PCBa. He do know that, in the literature, it is indicated that plants do take up &DT. moms 0641J3 53 DR. KOLBYE: I can't speak for that specific point. I don't know about the translocation of It. 1 would presume it can oeour, but I -am not competent to speak to that particular point. Does anybody care to answer that? DR. KEARNEY: We have looked for a number of years at residues in soils and translocation from soils into plants. In the case of DDT, ve find tome movement of soil residues into plant materials. It depends on many, many things, as you can imagine, such as concentration, plant species, soil organic matter, temperature, and a myriad of other things. What ha have found recently In the case of DDT -- which chemically mimics PCBa in many ways -- that the closer the material is to the surface, the greater the contamination in the plant from volatility. There is the possibility of PCB residues in soils giving rise to residues in plants, but depending on many environmental factors. DR. KOLBYE: I might add Chat this recycling of paper products situation may present us with a long-term problem in PCBs with respect to the manufacture of chip board and things like this which can come into contact with food surfaces. It is one thing to eliminate PCB from the National Cash Register Company paper but apparently there is not for PCB in the paper that is already marketed and recycled ao that these manufacturers cannot eliminate PCB entirely. So it looks like this is one of the more immediate questions the FDA has to face in attempting to regulate that exposure. iM fc iiim m k M i ' > >. sin ii i HONS 06811'* Bill Cook, do you have anything further that you would car* to add on the chemistry? MR. COOK: X have little to add but I thought I might addreas myself to a question that Dr. F.urger raised and two or three other points that might be of interest to those of you who may not be close to the laboratory. You asked about specificity identity. For us in Food and Drug this is very Important. As has been mentioned a number of times, the PCBa, 1254 and 1260 appear with the pesticides through the analytical procedura. Whan we do find PCB we separate them from pesticides. 1254 and 1260 are very easy to separata. We also have confirmation teats. These Aroclore are very stable to alkali, for instance, and wa go through an alkali test. Many of the pesticides such as DDT are easily altered by alkali. Besides that when there is e question one can use mess spectrometry. We don't do Chat routinely. A number of people have spoken about quantities. I think It is important to recognise that there are some problems of quanti tation, means of making calculations. Generally speaking, in fish the identity of PCB appears to be 1254 or 1260. Those chrcmatogrems do not look exactly like the chromatograms obtained from standards. Wc make a comparison of all of the area under the curve from a standard against all of the aTea under the unknown curve using either the electron capture or for the microcoulmetric detectors. We know of Instances in which people make their calculation from two or three peeks. I know one individual who makes hie calculations based on DDE as e reference. These different means of basing calcu- MCNS 060115 55 latlons will result In different values. " ~ One point on that carbonless carbon paper, both the Los Angeles and Seattle FDA Districts, and we In the Washington laboratory have done some work on a few of those pieces of paper. The lowest value we found was one percent by weight and the highest, from a copy of the Internal Revenue Service, Form 1040ES was 4.3 percent by weight of-PCB 1242. That is the chemical that was used by the National Cash Register Company In their carbonless carbon paper. They have their patent leased out to another company, Meade, and as far as we know now they too have discontinued the use of PCB in making carbonless carbon paper. However, as Dr. Kolbye indicated, this is going to continue to be recycling for some time to come. Somebody might even throw an old government file Into the veetepaper; this may contain forms containing PCB and thua continue to edd PCB to the cycle. We have not done any work on the penetration of PCBs into planta but I would guesa it would penetrate into root vegetables such aa carrots as is the case with dieldrin and there may be no measurable translocation upward Into the aerial parts of the planes. We In our lab have done e little work on the effect of ultraviolet light. Thia is a rough treatment. We knock some of the chlorines off; 1254 appears to become lesser chlorinated. These results have yet given ua any concern because generally speaking everybody throughout the world Is reporting In wildlife residues which look like 1254 and not residues with less chlorine like 1242. MOMS 068116 56 If there are any questions I will try to answer them. DR. MORRIS: I recall that during the early days of the Food Additive Amendment we received food additive petitions covering the uae of polychlorinated aromatics at; indirect food additives. Did these early petitions include Monsanto's PCBs, and if so, what was the result? MR. COOK: There was a petition for one of the compounds to be used as a component of an adhesive on packaging tapes. This was a chlorinated terpheynl, not a biphenyl. Mr. Ramsey could probably answer that better than I. MR. RAMSEY: Yes. It is allowed in e food packaging adhesive on the basis that there is no migration into the food. MR. COOK: When we apeak of aroclora we ere speaking of a mixture of chlorinated biphenyls, a mixture of chlorinated biphenyls and terphanyls or chlorinatad terphenyls. The 4400 aeries Is a mixture of the terphenyls and biphenyla, and the 5400 series ere the terphenyls. Those higher ones are solids that teem to be very inert. The lower series such as the 1221, the 21 percent chlorine Is even water soluble. it la very fluid. . DR. HALEY: They also will produce chemical necrosis is they get Into the skin, the terphenyls. So they ere not innocuous. MR. COOK: I am not familiar with the toxicology that was presented on the petition. DR. KOLBYE: Are there any further requests to Mr. Cook? MOMS * * i, '\ . ; ` '- ` < ..imiajMH aB 57 I chink Che point about the terphenyle is that as fat as vs know chare is no migration. This can be checked. 1 think it would be interesting if the Food and Drug Administration tould declare the Form 1040 a hasard to health but 1 am not sure it would be appreciated by the IRS. DR. KRAYBILL: Dr. Lindsay has indicated to you that the status reports that we prepared, there are two of them -- the lest one appeared in December -- are now very much out of date. I . believe with information presented this morning that we have been scooped and this is a good thing since such information la most Illuminating. Another thought that came to my mind was the similarities in other areas of work such as research on the dioxona and some of the pesticides. In dloxon toxicology we encountered the problem of chloracne in occupational exposure and thia morning a PCB toxic response was mentioned that is hydropericardium. One may have some contaminants here ss one observes with the dioxins. The polychlorinated biphenyls contaminants occurring together with those from dioxins. If one looks over the various reports -- and there ia an excellent Swedish report ss well ss the FDA status reports - and realizing what we heard today, there are some voids in our knowledge, areas that we should explore to enlighten us e little more on the safety or the toxicity of these particular compounds. One thing we should identify are.the primary constituents MQNS 068118 of the residues of PCB. This Is e big talk. Of the 1,200 series, 427. and 68% and 60% chlorine compounds and so forth, fish, perhaps, as a food would be a good Item to survey In this identification. It would be helpful to know what chemical or molecular apaclas we are dealing with which would help us in making our assesament of toxicity more meaningful. As an environmental health scientist, one always thinks of the total stress. Accordingly, Dr. Worf mentioned here'this morning that he is collecting air level data on PCBs. 1 sure would like to see this data. There is some PCB water data, perhaps on potable water aupply. There may be some PCB levels determined in the water in the estuaries where the fish swim around. We should have such data. Mr. Rmssey previously reported the data on foods and food composites in the diet. A statement was made about fruits and vegetables aa to non occurrence of PCB. We have reason to feel that some of these classes of foods don't have the PCB residue, hence; we are talking largely about the meat, fish and poultry group, but that is one-fifth of daily poundage inaofar as total Intake of our diet. Another important aspect is that of human monitoring and Dr. Manner and Mr. tturse talked about this. The sort of information we definitely need is data on the body burden of these compounds. You .did hear about the levels in the fat or adipose tissue, liver, kidney and brain relevant to the study in South Carolina. It la most interesting to have such data but X wonder perhaps if one should not acquire data from surveillance MGNS 060119 59 acroaa the country to eee whether there ere any geographic differences, EPA has the monitoring system to do this. EPA hat the resources available in about 15 community study projects. They represent an excellent geographic distribution. The other thing one needs is some research on the effect of PCB on various cell systems. 1 think ve should study the effect of these Aroclors on certain human cell cultures. Insofar aa toxicity is concerned, In short term toxicity the response that it moat intriguing to me la the effect on the liver mlcroeomal enzymes affected by the Aroclora. An effect on the liver microsomal ensymes by the Aroclor^ one might study farther, since this has been done to e certain degree. The influence of dllantln and hexobarbital, which Interact with some of the pesticide compounds, have been explored such es DDT and dieldrin and lindane and compounds of that type aa well as carbon tetrachloride. These have an Important effect insofar aa synergism in their interaction, therefore how much do they potentiate which could have an analogous situation in real life. Another area la the teratogenic study on the Aroclors with certain teat systems, other than the chick embroyo. FDA baa done extensive work on s wide series of Aroclors with the chick embryo and reported a (tost of biological defects from these various Aroclors. Another area for study is the short term reproduction response, the effect on the fetus. This Is most, important. Last hut not least -- there should be some work taking place on the mutagenic effect of these compounds. Then Mr. Burse and Dr. Hatimer referred to 06*1*0 60 the metabolic studies snd here ve need s better ides perhaps, on the distribution of these Aroclors In the body, the metabolic rate, the retention times or turnover rates, and the excretion rate. Also we should have a bettei picture on the fate of these compounds and their metabolites as It appears in the feces and urine. This brings to mind the Identification of the Aroclor degradation products. Are the Aroclors broken down like DDT into metabolites -- such as DDE, DDA end DDD. In truth then what is the toxicity of these various metabolites? Nov we get into the long-term effects of these compounds and we lonediately think of the carcinogenic properties of these compounds end we were Interested to hear Dr. Kimbrough aay she was first to note a few bladder tumors. In this context, will these compounds attack other organ slice such as the kidney, the liver, the brain, et cetera. Experiments in chickens and rodents do not follow e characteristic pattern Insofar as reproduction. For example, the Aroclors teemed to be more toxic then DDT in these particular studies. I made an outline here thee you may want to consider on what 1 celled dissimilarities In PCD end DDT toxicity. We might cite some of these differences. A. Apparently Aroclors have five times the activity that DDT has insofar as effect on the liver microsome enzymes. To me this Is most Important. B. The reproduction experiments in the rodents and chickens which I alluded to* where I said the aroclors may appear to be more toxic then DDT. HGNS 060121 61 C. The metabolic** apparently are unknown at la their storage capabilities in the serum and body tissues. D. The adipose tissue levels in man of Aroclors seems to be lower than that of DDT. At least, looking at the data of Dr. Hamrier, he showed parts per billion levels in man in his surveillance studies. E. The aroclors are not as universally distributed as DDT and this has been mentioned by several of the Investigators. There is one other piece of information that caught my eye and that la in the teat work with Aroclor 1221, 1248 and 1268, administered at a dose level of SO perts per million. With Aroclor 1221 there was an 11 percent reduction in the sleep time. (hexabarbital used) With 1248, there is a 45-percent reduction of sleep time, with the 1268, there was a 48-percent reduction. So this would mean at increasing levels of chlorine content -- the reduction of sleep time goes up, again pointing up the importance of this interaction between a drug and a toxic compound, such as the Aroclors. Other data on toxicity is pretty well aumnarised in FDA status reports, and previous speakers here have given values on the LD-50, the effect on reproduction, etc. DR. KOLBYE: Are there any questions directed to l)r. Kreyhill DR. MORRIS: In light of the relatively small quantity of PCBs now being manufactured, it is difficult to understand how PCB has attained the same degree of criticality as DDT which has been manufactured in hundreds of thousands of tons, extending beck over three decades. Do we really know how much PCB Is now being produced? HONS 068122 62 Are there large sources other than Monsanto? The reported universal occurrence of residues Indicates there nay be sources which are currently unknown to us. , .. DR. KOLBYE: 1 don't think Monsanto has ever released data on what the volume of their previous production was. DR. MORRIS: I understand we have made some pretty good estimates. DR. KOLBYE: That may be. Who haa the information to apeak to that? I remember a meeting about a year ago In Dr. Burger's office where we couldn't get that Information. Maybe It is available now. Dr. Lindsay, that concludes our viewpoint, except perhaps for the suggestion that after the meeting today winds up and Is concluded 1 would like to suggest that va have eome sort of a continuing panel of representatives so that we can exchange infor mation. DR. KIMBROUGH: 1 would like to point out again that 1 do not want to make the statement that the PCBs ere carcinogenic. However, we should set up studies to determine whether they are carcinogenic. I would also like to raise another question; reports have been made particularly in the older literature where people have developed chloracne after they have been exposed to PCBs. 1 wonder if chloracne has been obaerved recently? Do the workers who worked with the fishmeal show skin changes? ' DR. KOLBYE: Does anyone have any Information of that point? It might be interesting to check into the Japanese poisoning cases, too. 06&123 hqhs 63 DR. NELSON: The Japanese do report that the poisoned show the colored individuals did have skin disorders. DR. WORF: I would like to direct a question to Mr. Duggan. I would like to know whether the cortaminated fishmeal is going to be disposed of in any regulated manner. What are the plans? MR. DUGGAN: The contaminated fishmeal, of which there is now between 1,000 and 1,500 tons, Is being collected at Wilmington. What will be done with it we don't know. This is the manufacturer's problem but it will not be used in food of feed. We will maintain control over It until It is properly disposed of, probably ss fertilizer. DR. KOLBYE: Fertiliser for non-food crops? MR. DUGGAN:- Are you going to enforce that? DR. KOLBYE: No. I guess that la our hope. MR. DUGGAN: On this fishmeal, in our initial investigation we did look for ?CBs in the fishmeal coming off the boat and going Into the pasteurizer. The results were negative. So it is not a general problem with fishmeal. DR. LINDSAY: Henry Verhulst, would you report on the Bureau of Product Safety? MR. VERHULST: I have very little to say because we are relatively new in this. We have tho responaibility for all products going into the home, particularly those that are accessible to children. Recently, we have begun a project to investigate if PCBs are included in the plastics, particularly in childran's articles. After today, undoubtedly, we will want to look into the matter of newsprint, dyes and otherproducts that are coming into the home. HONS 068124 Certainly all sources should be looked at as part of the total picture In tins of the problem that does exist. DR. LINDSAY: I suspect we had better take a break for lunch. After lunch we would like to hear from other agencies that are here and from individuals who are working in the area of PCB research. Dr. Hooplngarner and others will be heard. Then we will come down to the crunch; where do we go from here? Aa to lunch, .1 think the only advlee I can give you is that if you went for coffee, that is also the nearest place to have lunch. Any place else is quite a little ways off, except there are several "blind" stands on'different floors. We will recess now and we will need to be back here, under these circumstances, by a quarter after one. If there are no other questions, we will see you back here at a quarter after one. (Whereupon, at 12:15 p.m., the hearing was recessed, to reconvene at 1:15 p.m., this same day.) HONS 068125 65 1 AFTERNOON SESSION - DR. LINDSAY: If we get started quickly, we won't be but more than the ten minutes or so late that we were before. That Is pretty good. Mr. Dustan, I think we have reached about the point where since I think you know the gentleman Involved in other agencies better than 1 do, will you Introduce any Individual here from either Interior or NOAA, and ask them to give a situation report. MR. DUGGAN: The last PCB meeting we had was held out at Patuxent, hosted by Dr. Dustman and Dr. Stlckel. Dr. Dustman has been very much inter ested In this PCB problem since It first came to our attention. Dr. Dustman, would you speak to the point and have your group speak as they wish. DR. DUSTMAN: Mr. Chairman, Mr. Duggan, ladles and gentlemen, we have been familiar with PCBe for a very long while. In the very early stages we didn't know what they were. The eagles told us that they were there. We learned very early In our chamlcal meanderlngs to stay shy of them, and de veloped methodology at Patuxent that allowed us to split then off, ao to speak We did this by toning, and It has served us well through the years. I have with me from the Patuxent Wildlife Research Center, three people that I would like to acknowledge: Dr. Lucille Stlckcl, who is our environmental pollution research coordinator, and you will he hearing a little bit from her later on; Mr. Mulhern, who has recently published a method of separating suitably and measuring PCBs by use of a thin layer method, (this was published in JAOAC In Ma>}, I believe; and Mr. Haath, who is our Center blometrlclan, and also In charge of our toxicology work. He has carried on a number of teats, short term toxicity tests, using our standard test species, and also longer term tests, studying the effects of PCBs on reproduction. HONS 068126 66 Wa have as of last March a publication that la soon to make its appearance, entitled "The Occurrence and Significance of Polychlorinated Biphenyls in the Environment" that will be published in the Transactions of the North American Wildlife Conference that was held in Portland, Oregon. With your permission, 1 would like to read a susnary of this paper, some of which is well known to you; some 1 hope will be of such recant , origin that it will be new knowledge* This paper la areview of the litera ture: there have been several other reviews mentionedhere today. This one was written with particular emphasis on wildlife matters. It is some 24 or 25 pages in extent, and details those sorts of things that we are concerned with and engaged in in studies of environmental pollution as it relates to wild animals. Thera are several things hart in the summary that 1 think you will find of Interest. 1 am sure you are all aware that foreign scientists have given e fair amount of attention to PCBe, and I would like to start by mentioning that special studies in the Netherlands, and Great Britain,aa well es in the United States, have traced PCBs to industrial effluents, although other possible sources have not been followed. The use of PCBe In paints, cartons, and insulating fluids suggests that environmental pollution may be from many different sources. PCBs are present in fish and wildlife In many countries of the world. Quantities ere higher in animals living near Industrial sites. PCBs build up in biological food chains with increases of tens to thousands of times frca lover to higher organisms. This la of very great importance to those of cs who ere concerned with environmental effects. HONS 06812? h 67 Experimental studies have shown that PCBs have a toxicity to mallards, pheasants, bobwhite quail, Coturnix quail, redwing blackbirds, starlings, cowbirdf and grackles that is of the same order of toxicity as DDE to t'tese species. Overt signs of poisoning also are similar to those caused by compounds of the DDT group. Toxic effects of DDE and Aroclor 1254 to Coturnix chicks were additive, but not synergistic. PCBs containing higher percentages of chlorine are more toxic to birds than those containing lower percentages. And, of course, w have heard of the PCBs of foreign msnufacture containing contaminants to sn extent that greatly increased their toxicity. So we have contsmlnants that are contaminating tha environmental contaminant#, if you want to put it that way. Toxicity to insects of PCBs of different degrees of chlorination is the reverse of the pattern in birds. The lower chlorlnations are more toxic to insects. PCBs enhance the toxicity of Dieldrin end DDT to insects. Residues of PCBs in the brains of birds killed by these compounds measure in the hundreds of parts per million. PCBs My have contributed to mortality of some birds In the field. PCBs Induce microsomal enzyme activity in birds and mammals and the lower chlorinated mixtures have estrogenic activity in rats. This you have heard today earlier. Offspring of pheasants whose parents received high dosages of PCBs made poor choices in visual cliff tests, indicating that behavior was affected Egg production and hatching after pipping also were affected. Long-term studies of the reproductive effects of Aroclor 1254 on mallards and bobwhite quail and of Aroclor 1254 plus DDE on quail showed no HONS 068128 significant difference* from controls. This was work that Mr. Heath was responsible for at Patuxent. In studies of chickens however, egg produc tion, hatchability, and shell thickness were impaired by high doses of Aroclor 1254, and by low doses of Aroclor 1252. With- these few remarks, I would like to ask Or. Stlckel if she would come up and tell you a bit about what we have done, what we are doing, and what we plan to do at Patuxent in regard to studiea of PCBs. DR* STICKEL: Many of the principal findings Dr. Dustman has al ready covered. I think maybe the main point of our work that would be of eoneern to you la the demonstration of the universality of the occurrence of PCBs. There has been some feeling that PCBs may be only a local problem, but from the evidence that we have at hand, the very great extent of the distribution of these materials In the natural world is becoming increasingly clear. The PCBs have been present In substantial quantities In every bald eagle that we have analysed at our Center from the time we got the flrat gaa chromatograph. And the ones that have been collected and analysed from the years 1967 through 1969, where it has been possible to get an approximation of the amounts, contain quantities of PCBs that are of the same order of magnitude as DDE, which means that the averages are In the tens of parts per million, and the extremes In the hundreds of parts per million. There has been one case where PCBs probably were Involved In the death of an eagle, with brain residues into the hundreds of parts per million. Ospreys have been sampled -- both tissues of birds and the eggs that they lay MONS 06Q12S 69 In a number of area* along tha Atlantic Coast. Connecticut osprey eggs contained an average of 16 parts per rilllion PCBs, with amounts ranging from 7 to 30 parts per million. Eagle eggs had an average o'. 10 parts per million of PCBr and even in Alaska, 1.65 parts per mllllo'i. Ospreya eat nothing but fish and the fish haven't been through the processing plants to be directly contaminated by leaking heat exchanges. fl Eagles feed primarily on fish, but also eat some birds. So that they are working on the same food base that we are. We have also made surveys of woodcock, a bird that is of consider able Interest to hunters and that feeda altogether on earth worms. A wood cock eats an average of 75 percent of its weight a day in worms. Their tis sues on a fat basis contained an average of four to nine parts per million of PCBs. The worms they feed upon are living In the same soils where we are growing our crops, and again, these birds are a product of the same food baae that we depend upon. -He have sampled waterfowl nationwide; all samples have contained PCBs at various levels from low to high, depending upon the regions. The only birds that we have sampled that have not had PCBs In every sample are mourning doves. The breast meat of mourning doves, the Southern hunters will be pleased to know, are extremely low in all DDT products, PCBs, and mercury. So, if you want to go hunting, don't hunt eagles; hunt mourning doves. Tha really important part of our work, however, is not so much the MONS 068130 70 distribution of PCS* In the environment end the levels of residues that ere encountered, but the significance of these residues. Hr. Heath 1>i conducting research to determine the effects of the various formulations of PCBe on the reproduction of birds, end on their survival. The PCBs follow the standard dose-response relationships th.it have been found for other toxic chemicals and toxlcltles have been estab lished by problt.analysis techniques. The reproductive studies have not been conducted with sll the different formulations. There are some signs of species differences in response to PCBs, which Is also true for response to DDE. The species that ere sensitive to these two materials may be somewhat different, however For example, bobvhlte quell and pheasants are birds that are not susceptible to DDE-induced shell thinning except In e very minor degree. Their shells can bs thinned by massive doses. But, vheraas mallard ducks are sensitive to DDE, the opposite may well be true with PCBe. Mr. Heath's studies showed no reproductive effects of PCBs on mallard ducks at anything that would approach a realistic envir onmental lavsl. In contrast, the Monsanto Chemical Company's studies with chickens did show shell thinning as e result of dosage with certain PCBs. This has not been pursued sufficiently yet to be sure, because 11 the formulations have not been tested againat ducks end chickens at the same dosages; the cross-comparisons are still an approximation and may not prove to be correct. ^ In addition to these studies, we have special studies In residue kinetics, which are studies of how to diagnose the cause of death due to PCBs, determination of the tissues to analyze, end the critical residue MCNS 068131 71 levels. They also Include studies of how rapidly the chemicals build up In the ^issues and how rapidly the birds can rid their systems of the material. These studies are not very far along, so I can't give you any results at this point. We also have a chemistry laboratory which of course is basic to the success of any of our enterprises. Some of our first results have been published, giving the mass spectra and empirical formulas of 18 dif ferent PCB materials In eagle tissues. Mr. Mulhern's work with thin layer chromatography has led to a method for quantification and separation of PCBe. Mr. Bagly has made studies of the metabolic changes of PCBe in quail and these results are nearly ready for publication. An Important problem In chemical analysis was brought out this morning. This was that the pattern of PCBs changes in the animal body, and keeps on changing with time, so that quantification from total areas, using the Aroclor mixtures as standards will leave something to be desired in terms of accuracy. However, as nearly as we have been able to determine from the magnitudes that have been found In wild animal tissues by different people using different methods, it does not appear that different biological con clusions are going to be drawn. All measurments are roughly the same magni tudes; so that it's a matter of Improving precision. Despite the variations In methodology, it does not appear that they have produced misleading con clusions in the biological sense. I have been asked to call your attention to a publication, "Chlor inated Hydrocarbons in the Marine Environment," w.hlch is a National Academy of Sciences publication that Includes a discussion of PCBs. HONS 068132 m. ii i l. w w i l ii t[1 'li 1 l i1 l l^ 72 HR. DUGGAN: Since neither Dreeors Dustmen nor Sticket Invited question, I think they would both be willing to answer any questions that you might have of them. Are there any question? DR. WORF: I was wondering v*at the sources of polychlorinated hydrocarbon* are in the marine environment and is It possible that some of the sources might oe from ships that have sunk that have used tons -- lit erally tons of FCBs in transformers? I happen to be involved In the transformer plant operations a number of years ago and one of their main customers were ships that used transformers. Is this a possibility? I shouldn't really ask you. I would suggest that as a possibility. DR. STICKEL: There Is e possibility; however, quite e bit of work Is being dona in England and they have managed to trace PCBs to the sewage outfalls from industrial plants. This material has been taken end dumped In the Clyde Estuary, and In certain other places around the coast. It would appear that the levels of contamination in their fish were suffi ciently well explained by the amounts that were dumped. DR. HAMMER: Dr. Henaer, EPA. I Just wanted to clarify, did you say that woodcocks had the 49 parts of the PCBs, or the earthworms? DR. STICKEL: Four to nine. DR. HAMMER: Is that in the woodcocks or In the worms? DR. STICKEL: On the woodcock breast muscle. DR. HAMMER: What was in tha earthworms, do you know? DR. STICKEL: No. HONS 068133 . 73 DR. LINDSAY: Are Chere any other questions? - If not, we have Mr. Tom Carver, and Dr. Bnerson, and I believe someone else from the National Marine Fisheries. Tom, would you care to make a few remarks or would some cf your colleagues make a few remarks? MR. CARVER: I can do it from right here. Reo asked us in come as observers, and we can best do that by sitting down. The Service rather abruptly terminated lta PCB research program when Tom Dukes laboratory was transferred to EPA. There Is one other aspect that I should mention. The estuarian portion of the national pesticide monitoring program has been looking for PCBs in shellfish at about 170 locations around the country. This program is also conducted at Tom's laboratory in Gulf Breeze. The results In general you have heard earlier from Food and Drug. We have found PCBs In oysters at very low levels, and very Infrequently, and I think most of these come from Southern waters. I believe most of the elements of the national pesticide monitoring program have included PCBs in their analyses. Is this essentially correct? MR. DUGGAN: Particularly in the past year. MR. CARVER: Good. An the results of these studies will be printed in the Pesticide Monitoring Journal on a continuing basis, so maybe we can sell a few more copies of that. DR. LINDSAY: Are there any questions of Mr. Carver? If not, thank you, Mr. Carver. Thank you Reo. | That brings us down to people who are doing research. As 1 indlca curlier this morning, we asked agencies as we contacted them if they wished MCNS 068134 74 to bring in someone from outside the sgency that was either working under their funding or about whom they know and what they thought should be here. Vi brought two people in. Their names both begin with "H" so, if I go alp isbetlcally, 1 guess I have to go to the second letter -- in which case that puts Dr. Harris in front of Dr. Hooplngarner. Dr. Harris, from North Carolina State University, was one of the people that wc were looking to quite early in the episode of the Holly Farms chickens. Dr. Harris, could you tell ue e little about that -- and anything else? . DR. HARRIS: Thank you Mr. Chairman. We became interested in Aroclor when the inspection service began to pick up residues in poultry meet, after the New York fiasco. We had some teste underway to determine the toxic effects on poultry. On June the 9th, 1971, e condition in two-week old broiler chickens with symptoms similar to chick edema disease as described by Schmittle and Sanger was seen. The moat common symptoms were gasping and incoordination of the head and neck just prior to death. The most severely affected birds emitted e squeaking sound. The mortality ran to 50 percent and the remainder were stunted to the point that they were destroyed. The condition occurred in several broiler flocks from one day's feed production and no further cases developed. On postmortem examination, most birds had a severe hydropcricardiun with sufficient fluid in the peritoneal cavity to cause distention. A greenish yellow gelatinous-like fluid was found under the skin of some of the birds. The livers showed varying degrees of degeneration, with a mottled to s roughened appearance resembling cirrhosis. The kidneys were swollen MCNS 068135 75 nd pale vlch snail hemorrhages. Soma of the birds had whita cataoua-like material, resembling a bacterial infection over the heart and the liver. There was Inflannatlon of the Intestinal tract but no extensive enteritis. The digestive tract was usually empty. Becuase of the sporadic nature of the condition and the resem blance of chick edema disease or crofalarla poisoning, a toxic substance in the feed was auepected. Feed from houses with effected chickens was collected for analysis and a feeding experiment. Forty one-day old broiler chicks from the same parent flock were equally divided and placed In a battery brooder. Twenty were given free access to the suspect feed and twenty to a known non-toxic feed that Is routinely fed in the Department. The chicks were observed dally as to appearance, feed and water consumption. At ten daya of age, the chicks on the suspect feed were not very active and would huddle close to the source of heat. Feathers were rufflet and some of the birds were gasping. At fourteen days, half of the birds on suspect feed had stopped eating and would not move about In their cages. On the fifteenth day, ten birds died and the remainder were showing symptoms of gasping. The twenty birds on control feed were normal. All the birds on suspect feed were autopsled and had typical lesions, as we had observed In the previous birds dying In the broiler houses. In some of the birds, we were able to withdraw 45 ml of fluid from their pericardial sac and peritoneal cavity. A sample of the suspect feed was analyzed for chick edema factor, chlorinated hydrocarbon pesticides, crotalarla seed and polychlorinated biphenyls as McCune and Flick have described the latter as producing symptoms end lesions as we had observed. The North Carolina Department of HONS 068136 76 Agriculture's seed laboratory found no crotalaria seed. Analysis of the suspect feed contained DDE, 1.3 ppm; DDD, 1.42 parts per million; PCB, 148 parts per million; Benzene Hexachlorlde, 8.8 parts per million. Chick Edema Factor, negative. The principal toxic Ingredient in the feed was considered rc. be PCB. The only common denominator we had was fishmeal coming from the Port of Wilmington. We alerted the feed company as to the toxic effects they were having with their feed end the cause. We then notified the Departent of Agriculture, who has this In their jurisdiction. The grose pathology has been described in the literature by McCune, and we feel that based on his work, there is e synergistic effect between the benzene hexachlorlde we found and PCB. The main problem experienced by the poultry Industry was the effects on hatchabillty. Breeder flocks that produce the broiler chickens previously were hatching 88 percent and eome went down to as low as five percent. We did some analysia of PCB on chicken embryos. These were 14 oneday old dead embryoa. They contained .35 parts per million PCB. The yolk of fertile eggs contained .97 parts per million, and the fresh yolk aaterlsl from eggs prior to being placed in the incubator contained .29 parts per million. These ware all from breeder flocks that experienced lowered hatchability. We are doing the histopathology on the sections collected from those birds, and we*ll have reports on this at a later date. I will be glad to entertain any questions that you might have regarding the problems we have in North Carolina. HONS 060137 fW" 77 DR. LINDSAY: Thank you, Dr. Harris. I chink as Dr. Msrcsr observed earlier this morning, it is hard for a group of people getting up sequentially this way to leave anything for anyone else to say. Dr. Hooplngarnet from Michigan State University is a member of the tean that is working on the problem of mid-west meat kill, and I'll leave 1l up to him to deacrlbe more of their efforts. Dr. Hoopingarner. DR. HOOPINGARNER: Thank you. Dr. Lindsay. 1 come here by default. Dr. Ringer and Dr. Johnson probably should be here, but since they are on vacation, I won the toss. Michigan comes by this problem in a long series of events much like you have described. It starts back essentially with the opening of the St. Lawrence Seaway or before, when the alewlfe moved into the Great Lakes. This is a little rough fish, not too important, except when they die by senescence, and they pile up in great numbers on the beeches of Lake 1 Michigan and Lake Superior. To combat this, the Michigan Department of Natural Resources de cided to Import some game fish, since they had essentially controlled the 4 lamprey, which had been destroying much of the lake trout. These game fish made tremendous gains. Probably some of the greatest weight gains in re corded fish history -- at least so 1 am told. The first subsequent generation of coho, that is the eggs and young hatchlings, died in great numbers, in what apparently was DDT poisoning. That Is, the people in fisheries* Dr. Howard Johnson, said that this appeared to be what was happening. So they undertook an extensive program in moni toring of the mortality of the young fish. HOMS 068130 78 Of course* prior to this time they had also monitored the DDT or chlorinated pesticide* within these fish and had found quite large quantities of DOT. In fmet, so large that most of the fish were not allowed to be.shipped inter-state. In the subsequent years since the first harvest of the fish* the young were still dying, but now the symptomology had changed. This always looks like Monday morning quarterbacking, but essentially there was s confusion in the symptomology. This is when they started with the problem of looking for other possible contaminants: mercury, TFM, many of these became suspect, along with PCBs. The work is still continuing. About the same time, since the coho come to the wiers in tremen dous numbers -- and they have virtually tons of the fish available for the asking - and so they were fed to mink, primarily In Wisconsin, but some In Michigan. These mink fed the fish product had few young, and the young that they did produce almoat all died. They attributed this to DDT poisoning or chlorinated pesticides and they stopped feeding coho, A year ago, Dr. Ringer at the University decided to test just that hypothesis, sod he fed pesticides to mink in very high quantities, higher tu.m found In coho and he found no apparent reduction in reproduction in mink They had a few mink left over, and so they decided to try some PCBs. The analysis of coho showed about IS parts per million PCB. So they decided to double that level. They used ten parts per million each of 1242, 06813s mcns 79 1254 and 1260, and fad it to min'... They didn't fail to reproduce; they failed to live. This is where the research essentially is currently at Michigan State. . They are now beginning a new season feeding kits and leading up to a reproductive season, and ve have initiated a cooperative program with four of us trying to analyze some of the problems. The levels of PCBs will be much lower so that they can inhibit, they hope, reproduction in the mink. But certainly It appears now that mink are very, very sus ceptible to PCBs. While I'd at it, I might say what the rest of us are working on at Michigan State. Dr. Howard Johnson is concerned with the reproduction in fish (coho, and other game fish) in Lake Michigan. Dr. Matt Zabik is primarily interested In the analytical choaistry aspects, but also In photo decomposition. My own personal Interests are in the cytotoxicity to various cell cultures. Ve have a number of mantalian and insect cell cultures, and also interested in the so-called mutagenic effects, chromo somal effects, if you wish, to these same cell cultures. ' I'll try to answer questions as much as I am able. DR. KOLBYE: Dr. Kolbye. Have you observed any chromosomal defects? DR. IIOOPINGARNER: The program is just underway. DR MERCER: How long were the mink on the 30 parts per million before you saw the mortalities? DR. HOOPINGARNER: I will have to beg off this a little bit as 1 may be wrong, but it waa a very short time -- like 60 days, and they were dead -- before they could reproduce. ' MONS 066140 80 DR. KIMBROUGH: Renatl Kimbrough from Atlanta. You did not observe any porphyria In these mink by any chance? DR. HOOPINGARNER: they have uost of the tissues fixed, sectioned, stained, and are reading the slides at this time. I can't say for sure what pathaloglcal symptoms occurred prior to death as I don't know. And the fact Is, I think, to be honest with you, the death took them quite by aurpriae. They expected some Inhibition of reproduction, but not death. DR. SKWTI: What waa the ppm of the feed? DR. HOOPINGARNER: 10 ppm each of 1242, 1254 and 1260. DR. LINDSAY: Thank you. Are there any other investigators in the audience who would like to discuss their research, and particularly any part of that research that bears on the pert of the problems of the agency represented here today? If not, then we come down to the hard part: it has already been suggested this morning that there should be a follow up of this particular type of information exchange. At lunch I discussed with Dr. Burger, the possibility that the Office of Science end Technology or the Office of the Council on Environmental Quality might act as an oversight agency to provide coordination for this type of information. Such a sponsor might follow this meeting with a more definitive meeting that could be structured and divided into areas where a more productive and profitable exchange of technical de tails could be given. However, our exchange today leaves us with at least four areas of Inquiry. I think perhaps the first of these has been fairly well answered and I don't know that we need to try to recap too much. From the material given today, what do-we know about the Aroclors, or PCBs; but 1 don't mean to preclude anyone from speaking to that point. MONS 068141 81 A second one Is obviously; what don't we know that we should know? A third item then, of courue, Is how do you put these In prior ities? Lastly, and I don't know whether anybody today will want to speak to It or not, there is the area of needed legislation. T think that the Environmental Protection Agency may have some discussion they may want to undertake with regard to legislative hearings that have just been held. 1 know that Congressman Ryan of New York has been very anxious to get rather sternly repressive measures on the PCBs. But 1 would like to throw this open to discussion. I think per haps just to begin with, if Dr. Dick Gordon ss openers could outline some of the questions that need answering, and knowledge that needs to be gained. After him, I certainly would like to have volunteers. Dr. Gordon. DR. GORDON: It seems to me that there are three areas of inquiry: What don't ve know that we should? How do we establish investigative prior ities? And, what are possible legislative and regulatory remedies? I thought of five "d'b" and s "B" -- Danger, Degradation, Disposi tion, Disclosure, Discontinuance, and a thought on Behavior. I think the first question we might want to discuss Is do we have a clear and present danger, or do ve only have a potential danger? The mink experiment, for example, might be one of the few examples of acute mammalian toxicity reported for these materials. From the point of view of degradation, the PCBs were designed to resist oxidation under elevated temperatures, last much longer than the DDTs, et cetera. Therefore, the environmental degradation pathways need much greater elucidation. HONS 068142 82 I think another interesting question that cane up today con cerns disposition* What about the fishmeal? In general, what shall we do with contaminated material? How shall we dispose of It? For example, if we put tne fishmeal in the ground, from what we know we will not get rid of the PCB. If we put the fishmeal Into ordinary Incinerators, it Is unlikely that the PCB will do more than be volatilized Into the air. So the whole disposition of contaminated material is very much a problem. The problem of disclosure -- how much has been made, where is it being used, and particularly how much is being made overseas, how much is being Imported into the U.S.? Are other countries becoming alarmed? And so on? I think Ed Berger had some good thoughts that should be dis cussed further. There is the Draconian step of discontinuance. Monsanto, as I understand did just that in England. Whether they should be so directed or requested to do so in the United States should be resolved. In any case ve have a residual problem of no mean magnitude. The last point came from some of the wildlife studies. This work has impressed me over the years: because one of the greet things which the wildlife people have done Is carefully observe animal behavior; as a result they are able to note small changes. . We do not usually get from the ordinary laboratory animal experi mentation observations concerning long term changes in behavior particularly changes that might be very minor. Since the United States* population is oddicted to one thing or another, nicotine or cafeln and all these other things, the question of human behavioral change is one I think that Food and Drug and EPA should plan long term experiments on. MGNS 0681^3 83 We really vane to think more about this. Man la a social animal and reports dealing vith minor changes In behavior patterns should be fol lowed up. We all know that email residues In nervous systems can sometimes have very profound consequences. By way of summary, I made these points which might allow us to focus the discussion we heard today. Do we have a danger: what about the degradation of the PCBs? How do we dispose of contaminated material? What kinds of additional dis closures , as veil as exchange of information do ve need? And what kind of prohibition# ahall be requested or prosiulgated? Finally, can behavioral effects be used as very sensitive indicators? DR. LltOSAY: Any questions of Dr. Gordon? He was asking a ques tion of everybody before he eat down. Dr. Kraybill, of course, had already sumnarized in quite succinct fashion many of the problems that are left unanswered by the knowledge thac ve have, and he has had admirable Insight into this as the compiler of the status reports that ve have had. And I would Invite him, If he has any further items to add, to please do so. Do you have any comments beyond those you made earlier this morning, Herman? Or aoma you would like to make over? DR. KRAYBILL: We might comment further -- and 1 mentioned this morning -- the similarity in the chemical structures, to the dioxins. We know from work in our laboratory the Way the chlorine atoms are arranged around the nucleus; if you get them all arranged around one benzene nucleus this compound is not as toxic. So here one might consider the isomeric form of these compounds and I am sure that through our chemical studies ve'll be able to identify what specific chemical entity or what molecular species we are dealing with. MOMS 068144 84 Well, this eventually takes us to a point in studying molecular configuraiion versus toxicity. We know a lot about the dioxin toxicity, and this would be very helpful, comparatively so in Identifying the various molecular species and then assessing che actual toxicity of that particular molecular entity. DR. LINDSAY: When we wound up the Bureau of Foods' presentations, I neglected to call on the Bureau of Drugs. We have several representatives here. 1 just wondered if there were any comments they might have to make other than the fact that, "Gee, aren't we glad we don't have to mess with this/' Dr. D'Aguanno? DR. D'AGUANNO: We live in a drug oriented culture. The Bureau of Drugs has been primarily a drug oriented culture. We have been svare of interactions. We are barely touching drug interactions) outside of an occasional report in the literature on drug pesticide interactions In humans -- 1 guess these were animal studies, laboratory studies. This is the extent of what we have gone beyond drugs. DR. LINDSAY: Well, we trust you'll keep in touch with all of this now as it goes along. Dr. Thomas Haley la with us in the back of the room, and any fellow that has done ss much pharmacological work as he has done has some comments, 1 am sure. DR. HALEY: I'm Haley. V Yes, there's two things that I heard today that I think should be Followed up. First of all the sex difference. I didn't hear anything about that. DR. LINDSAY: Turn that up a little -- I think you said "sex"? HONS 068145 4 a liMHtifc 85 DR. HALEY: Yes -- the difference between the male and the female -- (Laughter.) . DR. HALEY: 1 believe there should be studies on castrates, and the use of hormones to see If you can restore the difference. Secondly, the decreased hematocrit and the decreased red cell count and the deposition of porphyria, means that the 4- aminolevulinic acid cycle In the bone marrow is being effected. This may be effected primarily in the same way that lead does It. I think the ALA synthesis should be studied in the presence of these compounds. It might give you a lead as to why this is coming about. * DR. LINDSAY: Thank you. Dr. Haley. Dr. Flick? DR. FLICK: 1 think I can apeak loud enough. We have found with the dioxin problem that the level of dietary fat played a rola In the toxic responses of chicks, that is when the level of distsTy fat was high, we did not get as much of s toxic response ss when we lowered the fat contsnt, which meant that we were facilitating lipid absorption and lipid component absorption perhaps all lipid-soluble components. On the other hand, when we added dietary bilesalt, this facili tated absorption at both levels of dietary fat. And X would suspect that perhaps the absorbability of the polychlorinated biphenyls could be facili tated In a similar manner. 0681'*6 HONS 66 Dr. Harris mentioned a while ego that the intestinal contents of the chicks observed in the Carolina outbreaks were essentially empty. We found this to be true not only with the dioxin studies but also with the polychlorinated biphenyl studies. /nd in both studies we found in the terminal stages, that the animals' Intestinal contents were essentially nil, and we never printer, but we've often discussed and still feel, that these terminal animals arc really dying in a stage of malnutrition -- in addition to other toxic responses at the enzyme or eubcellular particulate level. Again perhaps dietary composition should be looked into with respect to the polychlorinated biphenyls. With respect to absorbability, we found this to be true, in a recent report we gave to AOAC lest fall, that the absorbability of the dioxins were related to chlorine content. Again this may be a factor to be studied with respect to PCBs. DR. LINDSAY: Thank you. Dr. Flick. 1 think in getting down my list of draftees, it might be an appropriate time. Dr. Burger, if you have any thoughts with regard to what went on here today, and whet might succeed it? DR. BURGER: Dr. Lindsay, first of all, thank you very much. Let me* just take the opportunity of offering my congratualtions to you for -- and the Food and Drug Administration for having put on this meeting, which i think is a landmark of a success in bringing the right variety of people together at the right time on this Important subject. And 1 quite sincerely mean that. Our view of this, from my end of town. Is perhaps several-fold. On the one hand, one could say this Is a fascinating If academic case study of a scientific matter that impinges upon the public policy machinery. 1 MGNS 068147 87 believe, incidentally that our place in life, as someone described it. is the uarriage or estrangement between the scientific community and the public policy making machinery. . But think that Indeed this is representative of a matter which I la at the crossroaos of some public policy decisions. Let me Just ex plore a couple of these with you, because I think they are terribly im portant. It seems to me that if one were to sumnarlze much of what was spelled out this morning, and partly this afternoon, it deals with the probability of exposure of humans and of non-human elements in the envir onment. The amount of PCB material produced and its distribution in the man*s surroundings and the rest of the environment, the possibility of second order interactions such as magnification or changes In chemical i composition, and following from that, the biological availability to various species in the environment. I think these are all matters which illustrate in pert the com plexity of the question, but also illustrate in part the fact that some of what we are talking about can be reduced to what might be called an in formation question. There is a second kind of information question that has been addressed here. This is, given a figure of exposure to elements of the environment or a human being, what is the inherent biological hazard or activity that la involved? Perhape from those two kinds of Information, one then is in a better position to make some social judgments about whether or not this chemical material is a hazard or a matter of concern. Dick Cordon raised the proper point, 1 think, when he questioned whether PCB Is an established hazard or an Implied hazard. This, of course, is illustrative of really a long list of materials that are now in man's *ONS 06614d 83 environment. This Chen raises e series of aJdltlonal points such as the responsibilities of Che private and public sectors to do the research from which information is used to make decisions, the question of re* sponsiblllty of divulging information ah'jut production and distribution and toxicity, unexpected side effects, and so forth. And thirdly, (indeed the questions become more difficult I suppose the farther 1 go down this Hat) there la the matter of the responsibilities of the public and private sector for controlling the distribution end regulating the production of s materiel which is either implied or known to be of some concern or even hazardous. If 1 wars to beck up at this point, again, I would guess I am terribly Impressed that much of what we have talked about can be called an Information problem, end that having in hand the information about the amount of material that we are talking about and the ways in which It is distributed, aids enormously In making some decisions about how we view it. Dale, you raised the question of legislation. I fed there is a piece of legislation now pending. The Toxic Substances Bill Indeed was written In part 1 think to address some of these very questions. Fourthly, 1 guess, I would raise the matter of candor. Although the subject of this conference represents an area where there is a history perhaps of less candor than some would desire, I am impressed that this government does its business with greater public participation than many others around the world, I think I sense that the government Is expressing more cnedor than It has perhaps in several years. I think this meeting In fact Is an illustration of that trend. Finally, In order to be able to deal in a candid way with subjects like this, obviously the government is HONS 068149 89 In a batter position, the better armed it is with good science to back its decisions. Again, this meeting has drawn out of the walls I think an enor mous amount of effort and a great deal of diversity which has been terribly useful. It la really, I suppose, vowt frequently with this last subject, the quality of the science that goes Into government decisions, that our office is most concerned. Let me say quite frankly that. Dale, we would be very happy in cooperation with.CEQ if they would like, to be able to continue this session in depth and at langth. Thank you very much. DR. LINDSAY: Any question of Dr. Burger? tfe have covered now the executive sector. Let us go to the legi slative sector, I mean, from the oversight agency area. ' Dr. Muir would you care to aay something? DR. MUIR: Thank you. Dr. Lindsay. ' CEQ is an environmental overview agency of rather new origin. Over the past year the Council has attempted to evaluate the many various environmental problems. Well aware of the problem of hazardous materials. Including PCBs, we undertook a rather detailed study. The result was our Toxic Substances Report which was published this spring. If anybody Is not familiar with the report more copies are available at the office. A second product of this study was the development of the Toxic Substances Control Act of 1971, now pending In Congress, for which the Senate Commerce Committee's Subcommittee on Environment has heard testimony ov the past three days, in the first of two sets of hearing. HONS 068150 90 Basically what I want to do 1 juat quickly outline some of the provision* In the Act to show vhat la eivisloned aa a possible node for attacking the PCB problem, and problems associated with the many other toxic substances which have been and will be Introduced Into our surroundings. The Toxic Substances Control Act provides for the Administrator of the Environmental Protection Agency to regulate the use and distribution of all chemical substances. Xt further provides for the establishment of test protocols and testing standards for all new chemicals being produced In eonmardal quantities. As Dr. Burger has Indicated, one of the real needs in this area Is Information dissemination. Tht bill provides for full disclosure of manufacturing data with appropriate provisions for proprietary information. Xt will craata a chemical compound classification system, and Information storage system, to handle the kind of information that we heve brought together todey. Ae some of the speakers have mentioned today, there exists simi larities between dloxons and PCBe that should be noted. Xt le possible enelysls of these ehcmlcsl similarities could lead us to suspect other cleeses or other types of compounds that might cauee environmental hazards. This classification-information storage system will serve to make these correlations and will attempt to provide for technological assessment and the prediction of developing technologies and new chemicals. Through this provision, therefore, It la hoped that we will be In e better position to prevent adverse effects from new chemicals prior to their release Into the environment in large quantities. HONS 064151 91 Finally* the bill contains a section Intended to considerably expand research In the area of toxic substances. Now this problem la obviously very complex. Any new program in this area will necessarily have to overcome difficulties. Then; will have to be careful coordination of the existing authorities and agencies currently concerned with toxic substances. Further, careful consideration will have to he made to decide the appropriate point for regulation of use In the sequence from mining to retailing of foods. At the very least, this legislation is a good first step In the direction required to tackle the problem of PCBs and other hazardous chemical substances. I trill be glad to answer any questions that anyone would like to raise about this legislation. DR. LINDSAY: Any question of Dr. Muir before he gets down? Dr. Flahbeln, would you have any consents from a slater agency at HEW? DR. FISHBEIN: No. We haven't been involved, actually, other than scratching the surface on the development of the analytical method ology of chlorinated and other contaminants of the PCBs. That la the extent of our Involvement. DR. LINDSAY: For thoae of you who couldn't hear, Dr. Fishbein said regretably that they have just been scratching the surface. I think that implies they are going to dig a little deeper. DR. FISHBEIN: Yes, it does. DR. LINDSAY: Well, now, 1 think wc have come down to the gentleman that I want to call on next. I am always a little bit puzzled about just how to Introduce him, because he has been so many places and does so many thIngs. HONS 068152 92 Dr. Norton Nelson st one time, not too far back, was chairman of the FDA "Protocols for Safety Evaluation Committee." He Is now part of the EPA Hazardous Materials Advisory Committee. He has just retired as a member of the NIEHS Council. The main purpose In recounting these activities Is that they all deal with the kind of problems we are discussing today, and he has been so involved for as long as l can remember. I think that Dr. Nelson, if he will try a wrap-up here, and If he follows his usual pattern of stimulating a lot of questions can effectively conclude our discussion. I hope that those of you who don't have airplanes to make at 4 o'clock or some such time can stay and ask your questions, because X think that Norton will probably give us a good deal that we can continue to discuss. He will be the last Individual that I will call on. So, Norton, If you will have at It, ve would love to hear what you have to say. DR. NELSON: Thank you. Dale. Dr. Lindsay has opened up prospects which 1 am not prepared to fulfill. 1 really think that nearly everything that needs to have been said has been said and I see no reason to unduly prolong tha discussion. On the other hand, I perhaps perceive -- I am not sure 1 am right here or wholly fair -- a sort of uidaftemoon complacency descending over the assembled group. A compliment was given to Dr. Lindsay for his energy in putting this meeting together. I join this tribute. This meeting signals the im portance of the problem. Those who have spoken have presented some ex tremely Important information, and a considerable part of it Is new. Per haps that sense of accomplishment drawn from a job well done may tempt us to sit back and relax. HONS 068153 f I irnn n *namiv~ rui 93 Realistically, however, 1 do see a number of very great big gaps In this facing us in this problem. Thus, if I have anything to say perhaps 1 should attempt to point out the magnitude and significance of some of these gaps. For example, ve do not know ihe total production or use of PCBg in this country. Someone here may know this, I do not. These are vital data. Someone here may know how much foreign PCB is imported into this country, and used as such. Obviously we get some through finished products, plastics, at cetera. How much do we import as PCBs? I did not see In any of the presentation today an ordered des cription of patterns of usage, distribution, turnover and loss which might permit us to determine the chief environmental sources of PCBs. It Is trua that In ssvsral of the episodes the difficulty stemmed from accidents - thus, the misuse ms herbicide In West Virginia, the leaky pasturizing equipment in the fish processing, the defective meat transfer units that produced the Yueho disease In Japan. These might give us the reassurance that we are dealing only with such acci dents. I suspect this is not the case. These accidents have served the very useful purpose of alerting us, sometimes belatedly, to the problem by producing easily discernible consequesces. However, I sus pect that the wide spread environmental contamination may arise from continuing losses perhaps contributed to a series of accidental losses. This could be wrong; however, I suggest that we have no reason for feeling any confidence as to what the sources of PCBs to the environ ment arc. '* HONS 068154 94 Again, I believe ve have only very crude Ideaa as co the patterns tf movement of the PCBs from place to place, through the atmosphere and waterways. We really do not yet have good data on the stability of PCBs In the various transfer media, sediments, et cetera. I see this as a very Important consideration, not alone as it relates to future dis charge but also with respect to the persistence of present contamination now found In many places throughout the world. I am not going to speak of legislation. This has been touched on by Dr. Berger and Dr. Muir. 1 would say, however, that in our review of the sources of contamination, it may be determined that new regula tions will be needed for control. Again, we have talked about means of disposal of the PCBs or PCB containing materials. I suspect that there are not more than three or four incinerators in this country that are capable of successfully disposing of PCBs. In fact, 1 would suspect that most Incinerators simply take it out of what may be a sequestered location and distil it Into the environment where it is easily moved elsewhere. There are questions relating to the biological effects of the PCBs;'a few are fairly obvious. It is a remarkable clrcisnstance, and if 1 am wrong please correct me, that the present interim guidelines, which the FDA has established, were set without benefit of a two-year chronic toxicity study of the usual, and Indeed routine, type much less the fuller study that one would like to see with materials of this kind. Thus, I am not aware of any carefully done, chronic toxicity study that has been completed and analyzed and made available. MGNS 060155 -------------- Urn.. 93 I believe that there ere several chronic studies either near completion or perhaps recently completed. These will be very helpful when they become available. It is very clear that we urgently need carefully done chronic studies to ansver the question as to whether malignancy does or does not occur. We do have some data on the reproductive aspects, but this seems at best preliminary, rather than definitive. Indeed the frag mentary state of our knowledge of the toxicity of the PCBs Is empha sised by the work at Michigan State on the minks. ~ That work la compat ible with the concept that there is at least an order of magnitude difference in the toxicity of PCBs different to mammals. We have had discussion of the relative toxicity of the various Isomers of PCBs. Although I suspect that the gross trends we now per ceive will be sustslned by more refined work, my confidence doesn't csrry me to the point where 1 feel ve can rest on this kind of speculation. We need far more detailed study of the various isomers. Equally important is the question of contaminants or breakdown products; the chlorinated dlbenzofurans have been very inadequately studied. I have some other defects listed in my notes but these are the ones I see as being of major consequence. I hope that appropriate federal units will assume the responsibility for orderly steps to fill these and other gaps. Thank you. Dale. DR. LINDSAY: Thank you. Dr. Nelson. Are there any other contributions that the afternoon somnolence will let you make? Dr. Harris? HONS 068156 96 f)R. HARRIS: There Is some evidence, I believe, for certainly particulate explosion In the cities and this would fall out into the dust and dirt. I don't know if It would get into the food chain. OR. LINDSAY: Dr. Kolbye? DR. KOLBYE: 1 just would like to make a plea that somehow or another, we organize ourselves such that the flow of pertinent information concerning toxicology and residues is directed in such a way that the people that need to know this type of information get it quickly and can have it as a factor in their decision-making. I don't know what mechanism to suggest on this, but I would like to have It considered et thle meeting,, pleese. DR. LINDSAY: Any response to Dr. Kolbye's question right now? Dr. Dustmen? DR. DUSTMAN: I think It wes about two years ago, If my memory serves me correctly, that a small group of individuals met in Duluth, Minnesota, for the purpoee of exploring where we stood with PCBs and what we knew about them. The meeting was called by Dr. Don Mount of the National Water Quality Laboratory, now a member of EPA, end It eterted out to be juat a few individuals who were interested that were going to get together for the purpose of seeing what ve knew. And It grew into a full-blown meeting et which time quite e few university people were rep resented end e number of government people. I don't see many here that were In attendance at that meeting. ' The Important part of my comment relates to the development of a newsletter that was at that time agreed upon that would be issued et irregular intervals as the attainment of new information would dictate. And I have before me one such newsletter. HONS 06815J 97 There have been three of these. They cover ell aspects of the PCB business. Dr. Mount and his coworkers, there at the laboratory, have taken it upon themselves to Issue this newsletter. It is one to which you should all subscribe if you wish to keep current on what .s going on in this business. It covers such things as analytical methods, environmental occurrence and fate, uptake, retention, other physiological effects, and toxicity. The most recent issue is rather a thick one. There are many contributors to this. It Is a very fine means of keeping up with what Is going on and I would make the request of you that you really tune In on this and give encouragement to Dr. Mount who has, on his own, taken this on as an assignment. His address is: Environmental Protection Agency, National Water Quality Water Laboratory, 6201 Congdon Boulevard, Duluth, Minnesota 55804 DR. LINDSAY: Dr. Kolybe? DR. KOLBYE: I think that is an excellent suggestion, and 1 would like to ask whether or not the resources of the National Library of Medi cine, Toxicology Information Program, can be placed behind this type of an effort as an urgent priority matter. DR. LINDSAY: I don't know. 1 had Invited Dr. Mlder here today but he had other priorities and wasn't able to come. I can't speak for the NIX but T would think that Dr. Rlssman'a group in the Toxicology Informa tion Program would be very much interested In participating. 1 would like to say In reference to your question just before, that I think a more proper way to get this interchange established, at least between the analyses that are involved here, would be for each of you people going back to your agencies to alert your agencies to this need. HONS 06815a 98 particularly If you believe In it, and then some effort may be made on the part of the individuals for whotr each of ua work as to some decision regarding such a committee. For example, something similar to the committee set up be tween Interior, Agriculture, and HEW v<th regard to the nitrite program. l)r. Leo Friedman is chairing that and he la not here to report on It. But that sort of thing I think Is very valuable, and something like that could coma out of this, Al, If that la what you had in mind. But I think probably we have the wrong people here to designate the individual! although we may feel to the contrary. VOICE: I think we need botha a committee to coordinate among the agency raaourcaa and I think you need a superb toxicology and residue information program that can ba disseminated broadly. DR. LINDSAY: No argument. Dr. Worf? DR. WORF: I would like to ask a question either of Dr. Nelson or Doug over here, whether there is any occupation or health data? 1 alluded earlier that I used to work In an Allls-Chalmers plant that liter ally had thousands of tons of PCBs In the transformers, which I worked on in the laboratory, as a control chemist there, and I just wondered if there is any possibility of getting data from occupational health. I Jim sure that NCR, National Cash Register, their use of PCBs in paper and so forth, there is n lot of possibility of data from these sources. Do you want to comment on that, Dr. Nelson? Is this reasonable? DR. NELSON: I am afraid I cannot really help you. There Is earlier history materials probably similar to these during World War II. 1 am not aware of more recent work which would relate to more modern pat terns. They are probably very poor. MGNS 068199 99 Maybe Dr. liaomer can respond Co this. My feeling la that there may be data there, but I do not have It and I cannot say one '/ay or the other. DR. HAMMER: Just to underscore that, when I was reviewing this problem for our branch last year, the occupational health data was very scanty except for the problem of akin disorders and the problem of liver, acute llveT diseases, at cetera. There was virtually nothing available from the occupational health literature, and I think the prob lem that those of us that are concerned with human health problems are having now with many of the toxic substances la that the kinds of ex posures one saw in Industry were reslly often very high, and they are useful for the acute clinical and sometimes chronic Illnesses, but are not very useful at the other end of the spectrum, a problem of picking up burdens and going from there. What do these PCB burdens mean? What is their long-term effect? We don't really know at present. But I found Just a dearth of information on human affacta. DR. LINDSAY: Dr. Cramer? DR. CRAWiER: Aa a toxicologist trying to design experiments and interpret the results to protect the public health as well as the environ ment, I have a few consents with respect to the problems of the Environ mental Protection Agency. Dr. Hammer haa just spoken about occupational exposure. Cer tainly If we had some Information on the effects of occupational exposures to humans ve would have Information which would perhaps be of use for predicting the chronic effects of acute exposure or acute effects of acute exposure. HONS 06B160 4& 100 However, I would hasten to add that wa raally should incraaaa the surveillance of the general population, because the general popula tion and occupationally exposed are not exposed to the sane coopounds in the sane relative amounts. He have dlseuased several times here the fact that ve have a biological modification of these compounds. Therefore, when you eat coho salmon or chickens you are not getting the same profile of compounds aa you get when occupationally exposed to the same parent formulation. This leads to problems in setting up experiments. What are we doing wrong in toxicology? Well, as you know, ve usually utilise analytical grade material that are going to be analysed by gas chromatography. What we should be doing la feeding animals the material which humans would be eating. 1 would also say that what ve really want to do is measure the total impact, and wa really naad, that la the Environmental Protection Agency needs, to follow the routes through the environment end test representative organisms elong the wey. For example, we broughe up the problsai of dlsposel incinerators. We are going.to get different pro ducts after incineration, catalytic processing or reprocessing paper. Certainly carbonless carbon paper may originally have 4 percent of a certain formulation, but it does not come out that way when it is repro cessed . These are things that perhaps we should consider. And If 1 could take one more minute of your time I think there is a great deal to be said for research into ranges of sensitivities mediated by age, sex, interactions and genetic differences. MONS 068161 101 We are dealing with 200 million people, we act up the better experiments with a few hundred aniaala The sensitivities of species are variable, just aa are the ages. The difference in toxicity of PCB to the mink and rat are, enormous. Car alnly the weanling rat Is more susceptible to the Induction of microsomal enzymes than older rats. Diets affect toxicity as demonstrated in the vitamin C and protein deficient animals. This certainly markedly changes the ability of these compounds and to modify other compounds' action, brings into play Inter actions with pesticides, drugs and alcohol. There is a considerable amount of information available suggesting chat polychlorinated biphenyls alter many of these actions. I would aay when you take all the toxicology data available and take some of these variables into consideration, one concludes that we really have very little information relating to potential health effects to say nothing of the long-term environmental problems. DR. LINDSAY: Thank you. This reminds me of two oversights. One is I had asked Dr. Gordon to make some statements, end then overlooked him on the Hat that I had. The other one was that 1 had tried to, on several occasions, reach Dr. Raymond Hoore, who la now In the Institute of Occupational Safety and Health, to get him here today, and falling in those two or three times; 1 am afraid I lost track of it and I did not follow through. So that is why we do not have him here, or someone from Occupa tional Safety und Health. Dick? DR. GORDON: I have the seme kind of feeling that Dr. Nelson was developing st lunch, that today la sort of an opening warmup meeting end It HONS 063162 102 could very well be that after circulating the papers, thinking, looking at the transaction, maybe reading the newsletter, ve might vent to sched ule e couple days more of an in-depth scientific kind of meeting in the fall. I feel that there Is a lot of stuff that Is in the works, and l think that some wider notification would be appropriate of some of the conclusions today to the scientific community and might be useful. You can always say, "Well, one more symposium," but thsre are national meetings and there is of course an in-depth meeting that could be summoned possibly through OST or CEQ. I just sort of feel that the review of data over time and the experiments In progress would be quite useful and 1 feel that that might be an appropriate thing to consider doing in three to elx months. DR. LINDSAY: Thank you. Nick, do you want to say something? DR. BOOTH: I don't know how important this is. Dr. Lindsay, but someone mentioned e while ago that they would be Interested In human toxicity data. In the library yesterday 1 came across an article in one of the recent bulletins of environmental contamination and toxicology. There was s reference that went back to 1939, and it was of Interest to me today to learn that there wasn't a great deal of information about toxicity of these compounds to man. And I was curious about this cita tion, because it said that thete were three deaths that had occurred from PCBe, and I think and similar compounds, and I believe It was In the Journal of Industrial Hygiene and Toxicology. It was unavailable in our library so I didn't get to check that out. DR. LINDSAY: Dr. Haley? HONS 068163 103 DR. HALEY: Talking about behavioral studies that the wild life people are making. It is a very simple thing for anyone to set up what I call a pidgeon pecking routine and study all levels. Nov this is again a bird, so I would suggest that night be an appropriate type of approach to the psychological effects of these compounds. There Is one thing that seems to have slipped under the floor boards. Nobody has talked about the possibility of the inhala tion hazard from these compounds. Ue are talking about incineration, where this will be disseminated out and be in the atmosphere for people to breathe. I an not so sure they don't even get it when they are filling some of these gadgets at Monsanto, or wherever else they are doing it. I would suggest a full scale program on the inhalation toxi cology of the PCBs be undertaken. DR. LINDSAY: EPA, take note. Dr. Hammer, you said you bad gotten some out of the particu late templing from the air, too. DR. HAMMER: I would like to tell my own experience the pest year, and underscore another way of getting together which wouldn't in volve any formal committee's business but simply Just taking advantage of each other's work end sbility and sometimes even reading what each other writes or calling each other on the phone, that one place where one really docs have a need for a multidisciplinary approach la In the trace or toxic aubatances, metals, synthetic organic materials, pesti cides. And 1 have availed myself quite liberally of the many excellent studies that have been done in terms of animal husbandry and In terms of botany, U.S. Geologic Survey, Water, FDA diet studies, to try and get some estimates of human exposure. HQNS 068164 104 I chink that although there Is a lot more information that needs to be done, that there ere elreed/ many people attacking this problem from many different ways, from many different routes. So that Is the first point, that you can use this for our own studies and also for modeling. The second point Is that EPA recently published a suanary of the Helena Valley area environmental pollution report and this will be published In the fall. This Is one area where again due to the requests of the State of Montana, people from many disciplines went out end studied e tingle geographic area. In this case there was e source, e smelter. And In addition to the gaseous pollution they studied several heavy metals, end many of us who were there were studying people and the environment animals. Whatever It is, 1 think ve ought to consider when ve plan our new studies to set if we can perhaps do our studies In the same place or in similar places, at least, and eo achieve better coordination. This wouldn't always Involve formal commitments. It's an attitude, an awareness that we can and must develop. Permitting us to get together so that several years from now we will have aowe answara to theae queatlona rather than getting off In different directions again. DR. LINDSAY: Dr. Morris? DR. MORRIS: Murrell Morris, Food end Drug Administration. Many of us here have suggested that we have several more years of research before ve know what to do about the ?CBs. One speaker dis cussed the proposed new legislation on toxic chemicals. May I suggest that, under our present Food Additive Amendment, either Mr. Les Ramsey HONS 068165 105 or Hr. Reo Duggan could, by comorrow morning, draft a regulation which would eliminate tho use of PCBe In food plants and feed mill*, the letter being Che principal known route of entry Into our food chain. Rather than quote the law, a copy of which I have before me, 1 will present It In simple words. The Food Additive Amendment ws: specifically designed and enacted to prevent unsafe levels of non-food substances from getting into foods, either by direct addlclon or indirectly by what ie commonly referred to aa migration. The Amendment specifically provides coverage of all.non-food substances used in producing, preparing, processing, treating, manufacturing, packing, packaging, holding, and transporting food. It has bean reported here and alaewhera that PCBs are currently being used as heat exchange fluids in feed mills, and that this "intended use results. Indirectly, In it becoming a component of food." Since it la a non-food substance which is not generally recognized aa safe, it is by law a food additive. And since Its safe use in feed mills is not pre scribed by a food additive regulation, it la also by law an unsafe food additive, the use of which is a prohibited act because it leads to the adulteration of animal feeds. Thus, the law on food additives not only provides for the seizure of products contaminated indirectly by unsafe food additives, it also prohibits acts which might lead, indirectly, to the contamination of foods with unsafe food additives. We do not have to look only to our seizure powers in order to prevent contamination of our food supply with unsafe food additives. I do not mean to imply by this suggestion that we could have acted earlier, l.e., before we had the facta which have come to our attention as a result of this conference. MQNS 068166 106 DR. LINDSAY: Reo is not here, end Les is. I know whet Reo would ssy first, "Could you enforce it if you had it?" Dr. Krayblll? DR. KRAYBILL: I detect from looking at the toxicity data that there la some disparity in our findings. Some of us have discerned these differences. Again, I hate to reiterate our whole experience with the dioxins on identification and establishment of purity and 1 would like to have some comments from the chemists here, perhaps Mr. Cook would like to address himself to this point. For example, with 2,4,5-T it depends a lot on how you process this compound and what temperatures you are using in the processing. So what I am getting at here is that we encoun tered such a problem inthe dioxin testing. With four different agencies in testing programs, ve ran profiles or we at least identified the type of compound we were working with as standards. This might be s useful suggestion to these investigators here, if they get together and indicate what type of Arodor they are dealing with and how much contaminant is in that Aroclor, because this will affect the end result of the toxicological response. DR. LINDSAY: Chemist respond? - MR. COOK: There has to been an overlap of chemistry and toxico logy. In the bureau we have synthesized a number of chlorodioxins, 2,3,7,8syametrlcal tetra which you will normally get if you produce 2,4,5-T from trichlorophenols. That Is the tetra which is fantastically toxic. It is down In the microgram per kilogram range, whereas our most toxic pesticides generally are In the range of milligrams per kilogram. Some of the other chlorodioxins nrc far, far less toxic than that, by a factor of 2,000. HONS 0681.7 107 We do not know whether we might run into vide variation in toxicity in the group of compounds that \iake up the large number of polychlorinated biphenyls. You would have to separate out each member of the series and test for toxicity. There may be a situation similar to toxaphene. There are 50 to 100 different chlorinated compounds In toxaphene that are closely related chemically. In producing toxaphene, the percent of chlorination Is extremely Important. When chlorinated up to 50 percent, for instance, the material Is not very toxic. When chlorination is in the range of 67 to 69 percent the product is s highly toxic insecticide, over 69 percent chlorination there Is s rapid fell off in toxicity. Nov beck to the chlorinated biphenyls, theoretically there are 210 possibilities for different isomers. There are people who are separating these and my hops Is that somebody will do some individual Isomer toxicity testing, which I think would be very important, 1 think this would add a good deal to out information, All these different Isomers are not present In the different Aroclor products. Arochlor 1242 will have e number of compounds in coamon with 1254. I don't think 1221 has much in coamon with 1268. But there are overlaps. And if one were to pick out the important individual compound in the Aroclor for which we do have some toxicity data, we would be a step ahead. DR. LINDSAY: Thank you. DR. LINDSAY: Dr. Riley? DR. RILEY: Dr. Riley, CSRS, Department of Agriculture. I haven't heard the question brought up today, and perhaps it ought to be considered, what are the alternatives to the PCBs. HONS 068168 10* Rev. It cm out during our discussion of these hut exchange fluid* that thar* nr* nor* expensive natarlals that can ba uaad la pro- caaalng plant*. Do wo havo good Information In this arsa aa to altarnata sac trial*, aubatltutaa for Kla and uhat thalr coat would bat Vbat ara tha long-tarn projeetloa far vhan altarnata aatarlala ean ba braught Into uaat Tha Indications that us tan to ba gattlng la thla esafaraaca, and uhat va ara haarlag fron paopla who ara working with thosa aatarlala ara that thla la an extraualy paralatant chemicals and It la going to ba In tha anvlronaant for a conaldarabla parlod of tins. Thank you. Dt. LINDSATt Thank you. . Dr. FllamerT DC. PLDIXEks Dr. tllaaar, ACS. U.S. Uputa.it of Agriculture. I would Ilka to draw your attaatloa to ona point la tha Nonaaato technical bulletin on aroclora. This follows up Dr. Cooks' coaaeat. Tor nearly every Aroelor asntloaad, a darker, lass pure variety axlata with abotit tha aaae physical and chaalcal characteristics, but lower la price. So 1 think that senahew, our toxicological study should ba related to these two grades. We talked to Monsanto about tha dangers of oxygenation In tha higher grade aroelor* to give dlbencefurans, but we don't know anything about the lower grade aroclora, what their degree of purity la sod whether they could contain dlbaasofuraaa. This Is one point. Tha second point I would Ilka to aaphaslse la that for those In vestigations, sad 1-don't know whether thalr synthesis la currently being HONS 068169 --vmtviuii.1. ii . |"i i". 109 attmnpted. but we need ton* radloactively labeled aroclora if ve are going to f )llow the environmental fate of these compounds* DR. LINDSAY: Thank you. Dr. Pilsner. . Anyone else? Dr. Hooplngarner. DR. HOOPINGARNER: This Is a comment Z would like to direct, maybe at the Patuxent croup. They said that they have seen polychlorinated biphenyls since they have been analyzing tissues. I commented about the coho that had died the first year, apparently from DDT poisoning, at least it gave those symptoms* Since that time, they give none of the DDT symptoms. Yet the level of DDT in the coho has not changed. DR. LINDSAY: Dr. Stickel? DR. STICKEL: I don't believe that anybody vho he* not been elose to the coho salmon probably is going to be very wise to say even one word about it. DR. LINDSAY: Are there other questions or comments? Dr. Pllck? DR. FLICK: I-would like to just mention once more, and that is again drawing on the dioxin problem of the past, perhaps still current. Is the setting up of a long term study with a view to determine if after exposure, is there actual recovery. Now we had ~ we did this with the dioxlnes In a short term study and wc found that after removal of tha animals from any dioxins, that their recovery did not occur. In fact, the disease even became more pronounced and more grossly manifested. So I think recovery -- ^ DR. LINDSAY: You mean of the ones that have been continuously exposed? HONS 0681JO 110 DR. FLICX: 7m -- and they vara compared with controls that ware continued on dioxins. So this type of approach perhaps could also ha carried over to PCBs to find out If indeed the compounds, radio tagged or not, persist in tissues, and are manifesting toxic symptoms some time after removal. DR. LINDSAY: That is tough. You are damned if you do and if you don't. Dr. Harris? - DR. HARRIS: I would like to say a few words. Dr. Gordon proposed one question, is there a clear and present danger? I don't believe that has been resolved. Ue are going back and doing a lot more pharmacology and toxicology on this, and it might be another year before we gain more knowledge. He had lethal effects on embryos, although they were chicken embryos, at one part per million, and although the hen's food received 20 parts per million, to me that is a hazard. And the people that processed this fishmeal are not schooled in precautions of using its they are completely ignorant of the hazardous material they are dealing with. They knew of the leakage, and Monsanto knew it; that is why they continued to ship more and more in, without any precautions. So I believe we have a present and clear danger. Time won't wait until you can generate a year's toxicology. DR. LINDSAY: True. DR. Kimbrough.? MOMS 068171 Ill DR. KIMBROUGH: T wonder IT there would he any point tn doing none liver function studies and some other itudion In the workers that have been working in the fishmeal processing plant, and whether this could be done maybe by the plant or by the State Health Department, and of course, they should also be checked for chloraclne. Other symptoms of toxicity Include alcohol Intolerance complaints of the GI tract, nausea. DR. LINDSAY: That is always tricky, of course, going Into a situation like that and getting the compliance of the company to build up a nice ault against themselvas later on. DR. HARRIS: This Is owned by the Peruvians. They have e dif ferent ballgame. DR. LINDSAY: They would probably load up eome of our shrimp boats down there. Are there any other questions? A little while ego Dr. Burger was very generous with his comments to me personally, and I am very much afraid mistakenly, becuaae 1 don't deserve eny compliments here* you do - the people who came. We set this up In e big hurry, and everyone who has contributed so generously of his time and thoughts to the conference deserves the compliments that Dr. Burger passed on to me, end I'm sure he doesn't mind me giving them to you on his behalf. I certainly appreciate you having come today. 1 hope that more will come from this meeting, that individual sessions tailored to tha particular talents and problems will emerge, and that from this we'll all be better off. Thank you very much for coming. (Whereupon, at 3:30 p.m., August 5, 1971, the conference was concluded.) HONS 06B172