Document ZBezm2xpKNLnpeqBJ0Q8oMRDY

>: ./ i ' .\ l I DEPARTMENT OF HEALTH, EDUCATION, AND.WELFARE TRANSCRIPT OF PROCEEDINGS OF THE INTERAGENCY MEETING ON POLYCHLORINATED BIPHENYLS (PCBs) Thursday, August 5, 1971 f \ i Dr. Dal* R. Lindsay, Associate Cockles loner for Science, Food and Drug Administration Chairman HONS 206506 transcript of proceedings OF THE INTERAGENCY MEETING ON POLYCHLORINATED BIPHENYLS (PCBs) ii * 'i iJ A r t1 HONS 206507 i i >t n n -- iir i i M l a i * i im ilirr a 11rtili* iT ii 11nri ATTENDEES COUNCIL 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. Plimmer Dr. Robert C. Riley Dr. Frederick R. Send Dr. Joseph S. Stein DEPARTMENT OF HEALTH. EDUCATION AND WELFARE Center for Disease Control Mr. William F. Barthe 1 Food and Plug Administration Dr, Frank N. Allan Miss Helen C. Barry Dr. Nichols H. Booth Mr. J. William Cook . Mr. Paul E, Cornellussen 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. Gueat Mr. Leroy Houser Mr. Kelvin H, Keath Dr. Albert C. Kolbye Dr, Herman F. Kraybill Dr. Dale R. Lindsay Mr, Donald R. Martin Mr. Joseph J. McGuire Dr. H. Dwight Mercer Dr. Murrell p,. Morris Mr. Lessel L, Ramsey Mr. Lavesa R. Shelton Dr. Kenneth E. Taylor HONS 206508 | |r|V.:J'L if| | i Wi-ninl rfi ^Jhlrt^d,t.^W^*V'ytt.y,-----.^^...__<i--_T Food and Drug Administration (Continued) Mr- Robert A, Tucker Mrs- Barbara Van Schoick Mr. Henry L- Verhulst Mr- John R. Wessel National Institute of Environmental Health Science Dr- Lawrence Fishbein Mr. William W, Payne Health Services and Mental Health Administration Dr- Vincent F. Maturl DEPARTMENT OF INTERIOR Dr. Eugene H. Dustman Mr. Robert G. Heath Mr. Bernard M. Mulhern Dr. Lucille F. Stickel ENVIRONMENTAL PROTECTION AGENCY Mr, Virlyn W. Burae Dr. Morris Cranmer Dr- Thomas W. Duke Dr. Douglas Hammer Dr. Renault! D. Kimbrough Dr. Douglas Worf NATIONAL OCEANIC AND ATOMOSPHERIC ADMINISTRATION Mr. Thomas C. Carver Dr. John A. Eroeraon Dr, Joseph H. Soares OFFICE OF SCIENCE AND TECHNOLOGY Dr. Edward J. Burger, Jr. NON GOVERNMENT Dr. Richard S- Gordon Dr. Thomas J, Haley Dr- J- R. Harris Dr. Roger A. Hoopingarner Dr. Norton Nelson Dr. Lawrence M. Rosllnski MOWS 206509 DR. LINDSAY: I am Dale Lindsay, Associate Consuls s toner for Science, Food and Drug Administration. I apologize to everyone here for the catch as catch can nature of this meeting. In discussing this late last week with the Consulssioner, he Indicated chat he thought it probably would be a good idea to exchange information between the agencies that are involved. The effort was so hurried that besides Agriculture, EPA, and FDA, 1 am not sure whether we have other agencies here or not. As we go through the program anyone who has anything to say -- and I would encourage you to have something to aay -- please Identify yourself by name and where you are from, for the benefit of our Stenocyplat who is keeping a record of this meeting today so that all of us may know what happened and hopefully there won't be any argument about who aald what. There is some problem, of course, about a meeting with as many technical terms as will be used here today. I have asked the gentleman to use his beat phonetic spelling and we will try to be sure that we can fill in for what he may jiot be familiar with. There la no program, no agenda other than the agenda I have discussed with representatives of the agencies we have talked to. The idea is to exchange information and I thought that probably MONS 206510 2 the best vay to do thia would be to ask each agency with a problem to 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 to do. We vlll leave that entirely up to you. The idea here is to identify interests, abilities to cope and to come up with some sort of a better idea of who Is doing what and what yet needs to be done and where it might be done. 1 think in the interest of time, since we are running late, I would like to have Dr. Senti present the Department of Agriculture's position reports. DR. SENTI: Thank you. Dr. Lindsay. As Dr. Lindsay has said, our meeting has been put together on rather short notice. We haven't hed 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 thelaat 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 Inspection 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 i for me to be up here this morning and talking about this. The only 1 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. y-pm ;i w, njmi nj i.ihwpjjiuh h. .mj n^im HONS 206511 j chink maybe LI 1 Just tell you how It came to our attention end what vc have done up until now. It might be helpful to you. We found out about thla on July 19, which waa two weeka ago Monday. We found out about It from representatives of Holly Farms in North Carolina, who told ua that they Wad been having hatchability probleraa with their breeding flock. The hatchability waa down very low In some caaea. As I gathered the information, they had done a lot of examination and teating to try to determine what their problem was. ` They had pinpointed fiah meal and PBCa in fish meal. They then had called thla to the attention of Monsanto, who I understand then contacted the Food and Drug Administration. Is 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 anyone knew what the real extent of the problem waa, although it waa known that other people in the area had hatchability problems and therefore probably used aome of the same feed. I forget how this came about but somehow we got an under standing that Food and Drug waa investigating the fishmeal plant and was going to furnish a Hat to us of the other purchasers of the fishmeal. We didn't really feel that we had enough information at that time to do anything dramatic on a national scale. We wanted to cam more about the nature of it. We waited to get the llat, which was furnished to us on July 22, Thursday of that week. It turned out there were 64 prime customers of the fishmeal plane, roosc of whom we could identify as being MONS 206512 fif'd in V 12 states and 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 limitations to test 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 awlne from every plant that waa working under federal inspection in the areas involved. In the meantime we found ouc 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 uaed the fishmeal for preparing fish feed 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 40 swine slaughter plants. We aet up our program. We told our people on Friday, July 23, to begin that day to pick up samples to send to our labor tory 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 icc. Wc had our labs all primed and ready to go and the samples begaln arriving over the weekend. HONS 206513 5 Ue began Co get analysis about the 27th. During what we would call the CRASH testing program, yesterday we had had reports on 383 sanples. They include turkeys, broilers, layers and hoga. Ue have nut this morning, to my knowledge found a sample that exceeded the administrative guidelines established by the Food and Drug Administration, which is five parts PPM in the edible tissues of the bird. Ue 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 la the breeder fowls which wete 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 flstneal is 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. Ue went back to every plant in the 10 states and told them to take samples from up to 10 lots daily of I 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 momenc we have had no results on those latest samples. Ue plan to do continuing testing on broilers and we also plan to do some more tests on hogs. ' MONS 206514 6 When this first happened we v^nt back and 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 tloe. We found in our records 1 think one sample that showed low level PCBs somewhere about March or April out of a few hundred samples we 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 we will do until we get results on breeders. That is where, we are now. I 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 ask if my co-workers want to add anything to what 1 have said. DR. KIMBROUGH: ' Since the hatchability seems to be important, have you analyzed any eggs or are you planning to? DR. STEIN: We have not analyzed any eggs. I think that question would better be put to Mr. Duggan. MR. DUGGAN* Yes, 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 Farm 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 HONS 206515 7 present there. Some of them have been over the administrative guideline. Fortunately, those birds having that high amount were caught alive, killed and buried 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 is known? ' DR. STEIN: I could tell It but I am not the one to do it. Hr, Duggan could do a much better job. His people did the review. All I 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 Mr. Duggan takes his turn up here? . DR. BURGER: Yea. DR. FRIES: I was wondering if you had identified which this was, MR. DUCGAN: 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 10'/ percent 1242. We have heard some rumors it might be just a porLion of it but they said that particular food is as perfect as they can make It, although not 100 percent. DR. STEIN: Are there any other questions? MONS 206516 i'JiA 8 . Thank you very much. DR. SENT1: ' Another part 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 gjing on there. Dr. Riley of our research service will give a brief review of the activities in the experimental stations aa 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. ` We 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. CSPS has 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. Callfornla-Davis is studying the photo-dccomposltion of PCBs. Colorado is studying the occurrence HONS 206517 9 of PCB In sewer sludge and the breakdovrn of PCB in sludge when It is applied to the soil. Nevada is looking at the Influence of PCB on enzyme systems. Hawaii is working with the influence of PCBs in semi-tropic climate. Califomia-Riverside has developed a carbon-skeleton chromatography method of separating and analyzing PCB in the presence of DDT (J. Agr. Food Chen. 19, 396-398 (1971)). Also they are working with the fate of PBCs in the soil. They have a soil bank of 150 soil types, and are working with PBCs in six representative soil types. Ineidently, they are finding that PCBs are quite persistent in the soil. Scientists at Callfotnla-Rlverslde are also working with PCBa on vitamin D metabolism, calcium transport and calcium deposition in eggshells. In addition, the influence and effect of PCBs on parasite and predators, storage in fat, and biological magnification are being examined. Similar research on PCBs ia being conducted under a regional project 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 PCBs into the fo>d chain. There is considerable feeling that the burning of newspapers may be a mechanism that PCBs are widely distributed in the environment. The Geneva, New York station is working on PCBs in fish. Wisconsin has rather comprehensive work in the influence of PCBs on wildlife and some very specific projects are aimed at pinpointing HONS 206516 10 these Influences. I am happy to see Roger HoopIngarner and Dr. J. H. Harris here from Michigan and North Carolina. I am sure they will tell us about the work on PCBs 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 work. 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. SENTI: 1 think that just about covers in broad outline the kind of thing that is going on in the Department. Ue have an ARS iu our pesticide residues analysis. Ua have been concerned with PCB as it interferes with the analysis for other chlorinated hydorcarbons but 1 don't know that we need to speak to that at this moment. .( If we get into problems of analytical methodologiea this may arise. At this point 1 think 1 will turn it back to you. Dr. Lindsay, and perhaps you can enlarge some of the questions that have arlaan in the discussion. DR. LINDSAY: Thank you. Dr. Sent!, 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. We will have a record of this early next week, 1 believe. HONS 206519 ........... - '- n r i i i r i i n i i i i i T r i i r i 11 We will send the record around to the participants and you can take that opportunity then 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 I normally would because I am planning on getting a much better job from our Reporter. The logical agency to follow, I think, would be FDA. However, Dr. Duke of EFA 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 speaking for EPA to ace if they would like to move in at this particular juncture. EPA has not quite reached the same 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 goLng 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. HONS 206520 ip yrr 12 We have had fiah kills In Che Pensacola area and when this occurs we usually check dead fish for pesticides residues and related compounds. In the summer of 1969, we detected PCBs in some fish that were brought in. To make a long story short we traced the PCB, Aroclor 1254, to tha 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 I went over these quickly with you. This is a map showing the subject ares near Pensacola, Florida. (Slide.) You will notice the location of the Escambia River and Escambia Bay. The Aroclor 1254 entered the Escambia River approximately six miles from the bridge st Station No. 2. We detected it in fish, as 1 said, that were brought in as part of a fish kill. We do not ballave 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 residues. 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 206521 -'--^'tiWtlK iVi iiTT iit -s-j---,m- 1 13 In another cample, flounder liver contained approximately 76 ppm, shrimp, 1.5 parts per million. In sediment from the bay we found 1.7 parts per million. Sediment from the river outside the weir at the Montanto plant contained approximately 400 ppm. ' I will now back up to the original slide. (Slide.) In 1969 we sampled the sediment from the river to Station 4 and we 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 we 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 -- we found 55 parts per million in bottom sediment. This is compared to the 400 parts per million we 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 size and cheats try of the sediment particle. The finer orgsnlc settlements . have more PCB than tht! sand-sized grain. We have a shifting situation up there and I am not certain that our two grab samples contained sediment of exactly the 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. - -j ----------- r i b t i--------------- ^ -- - '1 - - - ^ MONS 206522 14 We found trace amounts, somewhere around .05 parts per million, in sediment near Station 6 and then surprisingly in East Ray, oTf the map here. About four miles up i:ast nay we found traces of PCB in the sediment and also under the Hay 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 7B 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 patta per million; eight to ten inches, 16 parts per million; ten to twelve Inches, 1.2 parts per million. We still find PCBs at the 1 to 2 parts per million whole body range in some animals from the bay. I think the general trend is that we are seeing some loss oT PCB compared to our 1969 samples. We are also doing some laboratory work on the toxicity of Aroclor 1254, 1: -*-- -- ..- , , IIIIM - - T Y i j ' - --------- --- TT*- W HONS 206523 , .. > **+ -t%; i ^*^PW '" Hifit tliJTlTiil'---- J V~Y 1i l aaema.*.<hm 15 ' X should mention first that **e have several investigators working on this at the laboratory and J. 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 at 5 parts per billion we get 72 percent mortality in shrimp over S 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.) Ue 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 opposed 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 bepatopancreas contains by far the greatest amount. We are continuing to work with this material in the laboratory. HONS 206524 16 ' At this time we are involved in observing the histopathology of shrimp and fish that have been exposed to Aroclor 1254 in the laboratory. 1 think that is about all the data 1 have to present, I will be glad to answer any questions. DR. LINDSAY; Are there any questions of Dr. Drake? DR, SENT1: You commented that the fish kill was not actually due to PCB? DR. DUKE: Yes. I think we all 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. Ua do not fael 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. Uorf 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 rcrong 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 area that needs to be done. HONS 206525 17 This group from EPA sre Dr. Hammer, Doug Hamster from our community health environmental group down at the Triangle, the Health Effects group. Just before Che meeting he gave me series of reprints of papers that his group had done and a:re responsible for. I think he may have a few words to say in summarising the work that this group has done and he will make aome recommendations for the future. Then we have Dr. Cranmer. I did not get a chance to talk to him. 1 just left a message for him to be here and I see that he is here. I 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: Yea, we are here. DR. WOP.F: I hope you will ha^e 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 cone up and if somebody else shows up you can take care of It then? DR. WORF: Doug Hammer, will you come up here, and then followed by Dr. Cranmer and then the lady and gentleman from Chamblee. I will leave It up to you for the rest. I think Dr. Nelson may be able to give us contributions at any time. . HONS 206526 ^irnflgllSstYar fi 18 DR. HAMMER: We have been concerned with PCB and our work la primarily epidemiological. We have s*'.udled PCS and other pesticide residue burdens in both urban and rural non-occupatlonally exposed blacks and whites living In one South Carolina County. 1 do have two extra sets of t^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, l.e. urban blacks, urban whites, rural blacks and rural whites. As expected, PP'DDT and DDE residues were almost universal. DDD residues were found in 84 percent of the people and Dleldrin was found in 63 percent of the people. PCB residues were found in only 40 percent of the people, with vslues ranging up to 29 parts per billion. Significant age effects, not always linear were observed for all residues except Dieldrin and PCB, Racial differences were marked for every residue ethnic-residence interactions were also the same except for Dleldrin. There were residence effects for all residues except DDE and Dieldrin, but sex differences only for DDE and DDT. PCB residues were more frequent and higher in whites and in urban residents. Residues were rare ir 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 ISO people in each group. Rural Negroes had an arithmetic mean of 0.3 parts per billion. MONS 206527 19 Tills again la only 4.3 percent of that population. Urban Negroes bad an arithmetic mean of 1,9 parts per billion. Urban whites bad 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 beings and also an industrial use profile of } three SAMA's in South Carolina, looking at certain aquatic and land animals and also fat and serum from persons having surgery. Summarizing, we have in our own small way been concerned about this problem and have been measuring PCB burdens in the general populstion. Clearly, we did find PCB present. 1 think we all know possible sources of these PCBs. All of these people were asymptomatic and there is no reason .to,,think they were ill. Nevertheless they are picking up PCB as they are many other pesticides. Are there any questions? i 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 autopsied people and we will be measuring PCI' In the liver as well as the fat and serum. MR. MUSSMAN: Have you found any correlation between the fat and serum levels? HONS 206528 I 20 n-- r--- ( -~-'--r i^r " ^ r i d l i A j u f c i O M i l ] DR. HAMMER: I do not have the values on the fat levels. The PCB levels In the serum did not correlate very well with the other DDT derivstlves In senra. '' MR. MU55MAN: But In no instance were fat and 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. FISKBE1N: Do you have a spectrum of the PCBs that are actually Involved? DR. HAMMER; Dr. Lamar prlestor of the South Carolina State Board of Health Is doing our PCB 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 has worked out a fine technique using five "finger prints" and gets about 90 percent of the PCBs present. - K would be happy to put you in touch with him because he really understands the method, and I am not an expert in It. They arc not easy to measure. ' MR. BURSE: What techniques did you employ in order to separate the PCB from the DDT-like materials? DP. HAMMER; He was using a methanolic calcium hydroxide digestion. This makes it water soluble, removing essentially everything but the PCB. DR. CRANMER: 1 might speak to you a bit about some of the activities at the Perrine Primate Laboratory li) terms of analytical methodology and toxicology of PCBs. HONS 206529 ^ 21 Dr. Frank Biros has utilized the combination of the mass spectrometer and the gas chromatograph to analyze mixtures of these compounds. Basically this concept Is a gas chromatographic separation followed by the 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 reprerentation of body burdens 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 various 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, Enos, 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, MONS 206530 22 One technique that Is showing promise in our laboratory is using capillary columns in the gas chromatograph prior to the mass spectrometer. This gives extremely good resolution, One doea 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 gas chro matographic columns and on the separators. ' Ve have had a considerable success when dealing with analysis in the presence of chlorinated pesticides, if one has a sample with DDE and DDT or several other compounds in the body fat perhaps even from some sort of drug therapy the problem is immense in terms of trying to ascertain the exact exposure to any particular formulation, if no selective criteria is applied. However, with PCB analysis just as with other types of analysis there is no substitute for good clean up procedures. Of course, 1 am not saying it is 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, at the Perrine primate Laboratory we are now including analysis for PCBs in our pesticides residue chemists* training course as part of the standard procedures because these compounds are showing up in so many human tissues In the monitoring program. 1 would like to say just a few words about the experimental animal work that we are doing on the interactions of PCBs on the toxlclties of certain pesticides. HONS 206531 23 One case that you msy Itc Interested in Is s vitsmin C-dtfie lent Quines |<ig. You get a fourfold decrease In the l.D^y of 1260 In aecorbutic guinea pigs. "* - A diet of 50 psrts per million of 1260 In the diet of a rat, decreases the fat storage of lindane by 75% probably through - microsomal enzyme accumulation but slightly increases the storage ' of p,p`-DDT. This is interesting since here ve have two pesticides, both chlolnated hydorcerbona, being effected in opposite directions in terms of their storage. The toxicity of the organophosphate Insecticide psrsthion is 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. Parsthion, is metabolized by two major routes. One is the direct detoxification and formation of diethylthlophosphate and p-nitro phenol. The second pathway first oxidizes parsthion to parsoxon which is then further metabolize to diethyl phosphate and p-nitrophenol. Then you break that up to diethyl phosphate and other materials. With pre-treatment with PCBs you get an Increase in the parathion to paraoxon metabolism rate. One might at first expect if you were getting more parsoxon that you should produce a more toxic situation. The rate of cholinesterase inhibition is Increased in animals pretreated with 1260, due to the more rapid conversion to paraoxon but the total depression of cholinesterase is lea^.since the biological half life is shorted due to the simultaneous Increase of the direct detoxification pathway. MONS 206532 24 In summary, I would like to emp'iftsize Chat PCBs have many Interesting effects, on the metabolism ani toxlcltles of pesticides and other compounds and one should avoid generalizations about the toxic effects which have yet to be described. Thank you. . DR, RAMMER: 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 is Interesting, 1 think the amounts of DDT required for no effect on your liver microsomal enzymes are approximately the same in the immature rat. I think you can draw some correlation. DR. WORF: I think next we will have Dr. Kimbrough and next her associate, Mr. Burse. Dr. Kimbrough is from our Toxicology Laboratory in Chsmblee, Georgia. ' DR, KIMBROUGH: Thank you very much. We have studied the toxicity of 2 FCBs, Aroclor 1254 and Aro- clor 1260 in the Sherman strain rat. Let me speak first of all about Aroclor 1254. The scute oral LD^q in adult rata la greater than 4 grama per kilogram. We also undertook a subacute feeding study in both male and female rats which included a reproduction study, 1 will just give you some of the results that we have now and If there are any questions I do have some tables that I cannot present but X can look up some of the facts. MQNS 206533 25 We found that 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 animala alao shoved leas weight gain. As far as the reproduction study was concerned, a definite effect on reproduction vaa produced at 100 parts per million. We did the first breeding after 76 days on the treated diets and ve 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 animala bom was slightly lower. When we did autopsies on these animals 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 I will mention later. We also found that some animala had porphyria. We found that in the male rats fed Aroclor 1254 it wss 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 ss 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 206534 2 f, . We also performed autopsies on the offspring. We found an increase in liver weight in the Fja generation of the- veanlinga at a dietary level of 20 ppm. -. We also gave some rats several, dosage levels of Aroclor 1254 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. 1 would like to give the toxicity data on the Aroclor 1260 now. In some of the animala that I have mantioned Mr. Burse has determined FCBs in various tissues and he will present his findings following this report. The Aroclor 1260 seems to be less toxic. We found that the oral LDjq 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 of 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 this feeding study the liver weights were not significantly Increased at any of the dietary levels that were tested. The reproduction, with 1254, wss definitely affected at 100 ppm. With 1260 it was not affected at 100 ppm but was affected at 500 ppm if the Aroclor 1260 was 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 i f1 t "ft 1 J'ltl iPS^ufynn HONS 206535 27 in'the urine and in five of ten femaleu at 100 ppm. We found none at 20 ppm in either aex. But with the 1254 ve did find it at 20 ppm in aome female rata. We also dosed sene animals with various dosage levels of Aroelor 1260 daily during the 7th to the 15th day of pregnancy. The dosage level that gave an effect waa 100 mg/kg/day during that period. The number of the offspring born and the,, survival of the offspring was reduced. "TKe findings that were made when the liver was studied can be divided into different parts. One is that the liver cells are enlarged in the animals that have received Aroelor over a period of time. This occurs with 1260 as well as with 1254. In addition accumulation of fat is found in the livers. Some of the changes that have been described with chlorinated hydrocarbons such as the Inclusions within the liver cells and the so-called margination can also be observed. At the higher dosage levels (1/10 males and 6/10 females at 100 ppm Aroelor 1254 in the diet for about 8 months. 1/10 female rats at 100 ppm Aroelor 1260 in the diet for 8 months, none of the males, none at 500 ppm. but several at 1000 ppm) a very pronounced change is found which has been termed adenofibrosls. There are different opinions on what adenofibrosls represents. It consists of fibrosis in the livers concomittant with a proliferation of cells which by some are considered to represent proliferated bile durca. Others feel that they represent undifferentiated hepatocytes which proliferate when destruction of differentiated hepatocytes occurs. . In many of the livers I also observed a brown pigment which A I assume is porphyrin. We did find fluorescence in these livers st autopsy. HONS 206536 Occasionally other organs showed change*. In some animals hyperplasia of the thyroid was observed. The incidence of bladder cancer In our rats must be very low, but I do not know what the actual Incidence is. The animals are random bred. I have worked at the Toxicology Laboratory since 1962 ind I have until now never seen a rat with bladder cancer, but this doesn't mean that they could not occur spontaneously. I did observe two bladder cancers In animals that were fed 100 ppm of the Aroclor 1260. The signifi cance of this finding is doubtful at present. However, it should be Investigated whether PCBs have any carcinogenic potentials. Now, could I have the slides, pleasel This first one shows the liver of an animal that has received Aroclor 1254 over a period of 8 months. You can see the enlargement of the liver cells. You also aee quite a number of mitotic flgurea. Here is an inclusion in the cytoplasm which resembles inclusions observed in the cytoplasm when rats have been given high doses of chlorinated hydrocarbons. The FCBs seem to cause similar changes In the liver. In the next slide you see a normal liver of a control snimal. The next slide shows another stain. The previous two slides were hematoxylin eosln stains and this is a PAS stain. This shows the so-called "duct formations" which is part of the ad_nofibrosis. They are lined by hepatocytes which are reduced in size. ' The next slide, shows a very good illustration of the adenofibrosis. Note epithelial cells that line duct formations which sometimes contain a cellular debris. Increased fibrosis which is shown in this area ia also seen. HONS 206537 29 Tha next slid* is an illustration of beginning fibrosis. Some hepe:ocytea have dark nuclei and some of the "duct formations*' which concain a mucinous material are also seen. The next slide illustrates again the adenofibrosia which sometimes can form nodules in the liver. It has happened thst 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 destroyed. The next slide shows a fat stain which demonstrates the amount of fat found in these livers. 1 have done a little work with the electronmicroscope. Ue are planning to do some more work with it. Are there any questions? MR. BURSE: Mr. Chairman and ladies and gentlemen, I am Virlyn 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 FCB derived materials with emphssis on Axoclor 1254 and 1260 using gas chromatography In addition to other systems. We have evaluated three approaches to the separation of PCB from DDT-like materials, namely the TLC approach, using silica gel as an adsorbent, the Reynolds procedure, vsing florosil ad an adsorbent and the Armour Burke procedure. See Appendix I 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 eagles. HONS 206538 * 4 .1 i\ I 1 4 There. 1* tomething In Che urine o Experiment C (Appendix I) chat I think la worth mentioning. We combined selected aamplee from the urine study and examined them by mass n-ect route ter and found the usual chlorinated cluster. We found clusters at 254 mass units, st 288, at 324 snd at 358. There was an Isotopic cluster which was Indicative of four chlorines that we found at 304. Initially we were trying to figure out what could possibly give s molecular weight of 304 and have an Isotopic cluster which was Indicative of four chlorines. We know that It cannot be poly chlorinated biphenyl. About two weeks after this work was done I was looking through Food, Cosmetics, and Toxicology snd found a paper by Dr. Vos from the Netherlands. This work was a follow-up on some previous work that he had done with chicks published In Toxicology and Applied Pharmacology. He was looking at the Aroclor 1260, the Cermsn product, the French product and the American product. He found discrepancies In the effects of the dosage levels of these three compounds. The two forelpi products fell more In line together and the Monsanto product was quite out of line, with the total effect of the Monsanto product being just signs of porphyria. He assumed there was something In the two forel#i products that resulted In the anomalies he was seeing. After he fractionated these two foreign products on florIs11 he was able to find the tetrachlorodlbenzofuran and the pentachlorodlbenzofuran as well as some chlorinated napthalenes. HONS 206539 The 304 does fell in line with the tetrachlorodlbensofuran. However, we have not been able to confirm one way or the other that this Is 304. I have taken the Monsanto product, Aroclor 1254, and fractionated It from florlsll, looked at the elution patterns by conductometric detection, and eluted until ell the PCB pattern uaa none but hsve yet to look at It on the mess spectrometer. This -Is work that is pending. We have also done some work relating to reproduction studied with Aroclor 1254 end 1260.(Appendix II) We plan to continue efforts to isolate constituents of Aroclor 1254 In the standard as well as Isolation of constituents of Aroclor In body fluids to determine what la 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 as well as low. Two additional procedures using TLC will also be evaluated for separating PCB from DDT-like materiel. One involves chemical degradation of DDT-like materials end the other Involves triple development on TLC using Kleselguhr which la a method that Dr. Vos from the Netherlands has published In the Bulletin of Environmental Contamination and Toxi cology. DR. WORK: Thank you very much. I think Dr. Llodssy has suggested we have a coffee break. Befor* we do this I would like to thank the EPA people who made the presentation here on very short notice. I think this Is good hard data. There are some gaps in the EPA program that we could not Include. We do hsve a strong program in monitoring this type of a chemical In the envlroment, both In the vster end In the air HONS 206540 r 32 and in.the aoll and In tlssua. The tissue pert was pretty well described here today. DrT Pyindle .of our Water Hygiene Lab unfortunately la not here an*? has had considerable experience In monitoring and . developing techniques and sampling techniques and Instrumentation for determining PCBs In water. With this I think we will take a coffee break. . DR. LINDSAY: 1 would like to suggest that, as a possible vey of getting some of this technical and detailed Information more completely disseminated, perhaps we can summarise from the pcdlua and then, if Its all right with the people who are providing It, we can amplify this for the record. We will try to get distribution to everybody that Is here without jeopardising publication prospects for It later. This Is strictly an lnteragenty type of exchange and I don't think this will constitute jeopardy for the later publication or acceptance by some critical educators. . We will take a short coffee break and be back here by quarter of eleven. .' . (Short recess.) DR. LINDSAY; As I Indicated earlier, there Is no agends. We are trying to play it by ear so I will reiterate what the "no agends" is. We Still have aeveral 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 some of the people from outside the Government who are working In this field MONS 206541  p p ^ ^ p p y ip p p p p jp w B B i^ ^ ^ I 11 33 of PCB research who can review some of their 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 soma of the problems thac 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 Rrayblll Is primarily responsible for getting these together In the Food and Drug Admin istration. We 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. We would appreciate It very much If each group of people would noc take copies for everybody but get only what you nead. I would like Mr. Duggan to give a situation report with regard to the Food and Drug Administration. Just before we go Into the activities of the Bureau of Veterinary Medicine I would like to ask Dr. Sentl to introduce a man ha discovered was 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, *.** MONS 206542 i i m w i n i- m j " "l- lj p r n r n m v m m ^ P ^ Sow we ere right In the middle of one of the emergencies. I think 1 will start off by giving the FDA regulatory policy on PCBs 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. 1 think this is the key. In this particular instance of poultry we have advised the Department of Agriculture that ve will not object to the marketing of poultry that contains 5 parts per million in the edible portion or 5 parts per million in the separate fat. That means that any '! time the fat is separated out during slaughter or processing as a finite substance to be used in other food products the 5 parts per million guideline will apply. In terms of animal feeds we have advised them that the us of feed ingredients contained in detectable levels of polychlori nated biphenyls for food produced in animals is neither approved nor condoned by the FDA. Such adulterated feeds can be used for animals not used for food purposes provided it' is not toxic to those animals, or for non-food purposes such as fertilizers 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 HONS 206543 residues ii. milk. We gave then a 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 te prevented. In one Instance 1 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 their rights of way and dairy herds had been graced 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 1 think properly contained the problem of marketing PCB contaminated poultry and eggs. 1 do not believe we ever finally nailed down the source of that contamination, though there was aome 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 pVeaent problem. Friday afternoon about 5:15 on the 16th of July the Monsanto Chemical Company called and said they just wanted to tell me that there was an awful lot of fish meal in the State of North Carolina that was contaminated with PCBs and that the company HONS 206544 36 Involved was the East Coast Terminal. With fish meal being used aa an animal feed and with the accumulative effects Into the fat of animals, ve 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 PCBa were doing in a fish meal plant to begin with. Fish meal la 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 pasturiseing 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 seems that fish meal has a facility for eating holes in these screws. After some investigation we found that this had probably started occurring about the end of April and they had been fixing thar screw off and on during the process. Later on it developed they had refilled or used about 5,000 pounds of aroclors in the month of June. We found chat they had shipped about 16,000 tons from the end of April until the 16th of July. We dfid request embargo! by the state organization and began to list shipments. The manager of the plant did not seem to have a whole lot of authority. Thia'ls why Monsanto finally called us up. They a HONS 206545 had known about this 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 realizing the significance 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. We had had a guideline for the New York incident, but we had told them it was not applicable to any other situation. This then meant 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 Tuasday. He iimnediately saw the gravity of the problem, particularly in light of the fact that this la used at abqwgrtwo percent in poultry feeds, which means that there could be f " ' we$L over half a million tons of contaminated poultry feed in the system. He stated that he would have to go back and discuss whst he was going to do vlth the plant manager, who happened to he In Peru at the time. Apparently this is an integrated operation too, end these firms are owned by Peruvian interests. They are not, as fsr ss HONS 206546 i,u m.twi iiiniw ewM' rgif-iiijrrffi --., afr.<t. , 38 we can determine, a pare of the Peruvian Government. At any rate, early Wednesday morning he advised us that he had issued telephone instructions to all of his consignees asking them to return all unused fish meal to the North Carolina plsnt 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 be produced from this. We are also looking to determine what happended to the eggs that did not hatch, whether they got mixed up into the incubator reject rsck or if they went for industrial purposes as they are supposed to go. This is pretty much where we stand at this particular moment. 1 think one thing we must recognise here is that we are not dealing with quite the same problem as 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 a fact. Unfortunately it has fanned out into a major problem. We are not yet at a point in our toxicology information where we can establish a guideline for all foods. 1 think we are i'* s gof|tg to. have to continue to deal with these other circumstances inWived in each case. It is not an entirely satisfactory system, but until we hava a better system 1 think we are stuck with this one. I think that is about all I have. I will be glad to try to answer any questions anyone might have. HONS 20654? * 39 MR, BARTHEL: What levels did you find in eggs? Mr. DUGGAN; We have not put that together yet. We expect to have a fix on that about the latter part of the week In speaking of this, as you know, PCBs 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. I have enough confidence in the ability of our field laboratories to believe that if there had been any substantial amounts or abnormal amounts, let us say, approaching detectable and measurable levels of PCBs in egg samples generally we would have heard about.it long before now. We do not believe there should be any detectable residues in eggs. Tills works out, 1 understand, to about a .5 parts per million guideline. DR, BURGER; Just to make sure I 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; I 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 aet to deal with specific instances. If Joe Stein calls me up next week i i <IF" JSW rn P nw.TJ'wni I-- m; . , HONS 206548 /^flHPXSVl* -V WWl^t- **>" ^jr'n'jc* * 40 and tails me he has a problem with PCBs In turkeys In California, for example, then we are going to get the circumstances surrounding that particular instance and then we will look at it in terms of the new toxicology we might have, how it could have been prevented, and then, deal with it on that basia. In other words, these guidelines that we have talked about here today are not across-the-board, DR. BURGER; la there a systematic scan for PCBs in fish at this point? HR, DUGGAN; Yea, they will be picked up in the multi residue methods that we commonly 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 Bureau of Poods who can talk more specifically to that point. DR. BURGER; A. final question. Did 1 understand you to allude to an industrial use of eggs? MR. DUGGAN: Yes. - DR. BURGER: What is that? MR. DUGGAN: I think they use eggs in the manufacture of tanning, preparations for tanning leather. This is one use. 1 suspect there are other uses as well. ' DR. BURGER: Thank you. DR. LINDSAY: Dr, Sentl, would you introduce our next speaker. 1| | | | | | | |jLyImj_ U :j lj__1 ... [ ^ - ---- - HONS 206549 . r- 41 DR. SENT1: We have Dr. Fries here of our Animal Science Research Division who has had some experience with the feeding of PCBs to livestock and he will give a brief summary.of that work. DR. FRIES: 1 will cover this very briefly. Last summer 1 was called in to give advice to a farmer who had been taken off the market because of excess DDT In milk. 1 decided to use this as . a field study. It wss 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 source of PCB wss silo paint. By coincidence the cows had been taken off the contaminated silage at about the same time we removed them from the source of the DDT contamination. We were able to follow the levels of both contaminants for a six month period. We sampled the cows individually every three weeks through the decontamination period. When a cow is.removed from PCB contamination, there is a 50 percent drop in the level of the milk within ,about the first three weeks. This is very similar to DDE. Then there is a slow rate of decontamination as the PCB is removed from body fat. This rate is about 1.3 percent per day. This is identical to the DDE. In fact, any grouping of cows you take -- individual ccjs varied very little but on any average group of cows ttv; two compounds behaved identically. That pretty well summariees the field work. We are now feeding Aroclor 1254 to cowa at Beltaville to establish relarlonahipa between the input and excretion in the milk. HONS 206550 iillrin "AJC- Sr.f^k,.rw^ .-2W .. ^ 42 -" _ Arochlor 1254 has been used In silo paints and Is probably the biggest PCI) 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. 1 might alao mention that Dr. Bitmap's group at Beltaville la 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 enzymes. I am not prepared to talk about their results. 1 do have a mimeographed summary of this field study. If someone is interested in the details they could write me for a copy. Are there any questions? DR. HOOPINGARNER: I was curious if activated charcoal would help reduce thia quicker? DR. FRIES: No. In fact, that waa part of the atudy. 1 have a disagreement on thia subject with one of your colleagues at Michigan State. That la part of the atudy and it la Included in the mimeograph. They had activated charcoal on the farm before 1 became involved. We fed activated charcoal in combination with phenobarbltal aa well aa phenobarbltal alone. Neither treatment had an effect on the rate of decontamination. I would suspect that if somebody had contaminated ullage and fed activated charcoal with it, they would reduce the PCB level in milk by at least 50 percent or more. I have looked at a number of other farms having these silos, in general It la a borderline situation. Some of the time --------- I I 1 II - I f 1 Jllllllj JI lP I I I [I '.win HONS 206551 pf *' rr-^a" mq- 43 during the allege feeding period the milk level la under the guideline and sometimes It is just slipping up over It. The levels are reasonably comparable to the levela that have been reported In Ohio where they have been taking some dairymen off the market. DR. STEIN: In running your field survey did you do any biopsies on those milk cows! DR. FRIES: I didn't do biopsies on the field survey. I am doing biopsies on the study I have underway at Beltsvllle. DR, LINDSAY: Thank you, Dr. Fries. Dr. Mercer, are you going to apeak for the Bureau of Veterinary Medicine? Will you tell us where you stand with it now? DR. MERCER: As with most programs which have a very loose agenda, if you are able to sit back long enough, whatever you have to aay 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 FCB problem. I was more or less prepared to talk about inavallable 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 a great 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 the data from Dr. Fries that probably gives us as much information as is available on dairy cows. I think it is well established that for a long time wc may have been HONS 206552 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 we do lave available on the toxicity of PCBs in 'domestic animals and poultry. There are a couple of papers that give a very good teviev of what is known about the toxicity of PCBs. Dr. Lindsay referred to the atatus report that Bureau of Foods, FDA, haa prepared, and which is available, which covera the literature up until the latter part of 1970, There is no point in going into a detailed discussion of this published Information. . A recent review article by Feapall and Lincer, the only one I 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 is known about PCBs. There have been some toxicity studies conducted in poultry. I believe the classic work was done by McCone et. al. 1962. I will briefly give you a summary of their findings. McCune fed chickens four-levels of PCB; 100, 200, 400, and 800 parts per million as component part of the diet. The chickens at the 100 parts per million level shoved no effect on the liver. They only showed a slight 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 cardium. 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 as quite extensive hydropericardium. HONS 206553 'i 45 ' ' There was also some work reported by De Nos and Kolman, 1970 on chickens receiving 200 and 400 parts per million for two weeks with a 60 percent chlorinated PCS, They found some effecta at both of these levels; kidney effects at the 20f parts per million level were extensive with hemorrhage and enlargement 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 is 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 a few toxicity studies done on ring doves where they have noticed some effects of FCBs. 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 thinking about regulatory guidelines. What kind of a tolerated dose can we afford to have. Dose effect correlation data is just not available. When you get beyond poultry, and get into the swine or calveB or sheep or any of the other domestic animals with which we Bie concerned regarding food production capabilities, toxicity and residue data gets extremely scarce. I do not -know of any information on these other species at HONS 206554 46 this point, if there is any current research going on in these areas I would b most happy to learn about It. It is certainly not in the literature. The other aspect that we need to have more information on is the tissue distribution and excretion pattern of PCBs. The best article that we can refer to in terms of published information on the metabolism of PCBs is an article that Grant et. al, published in which they did a metabolism study on rats. Again we run into this hairy question of extrapolation from rats to other domestic animals. They did report some interesting literature. Including evidence that PCBs were being found in human milk. This information has been substantiated in dairy cattle, where measurable levels did occur in milk. But basically I think the Grant work confirms some previous data that was given to us by EPA people this morning and that is that the primary organ of concentration in the rats was the fatty tissue. If you compare on a relative basis fat to serum, assuming the serium 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. The next major order of concentration was the liver, 59 parts per million compared to 1 in blood. The brain tissue, being the next In the sequenclal order of concentration, then the kidney, spleen, heart, testes and no muscle tissue showed measurable residues, - HONS 206555 I ' t- ... .-)tl ^.timi 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. I think thla 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 hydropericardium that occurred in early 60*a, is that associated only with PCBs or in the Bureau's mind is that associated with other factors? That was a major problem in the poultry industry at that time, DR. MERCER: I think in answer to your question that ve will feel much more comfortable as some of the data that is currently under way and the results become more available to us. Again, I refer to the work that is going on in North Carolina. I think ve will have some confirmation as to whether or not this was a sole effect of ?CB. At this point all ve have to go on is reported literature and you have to assume that this is what the major effect was. . DR. FLICK: I vss wondering if Dr. Gordon's question was pertaining to the chick edema disease which occurred in the late 50's and early 60's. This disease was not due to polychlorinated biphenyls. The evidence thus far indicates that these are polychlorinated dibenzo- parsdioxins and Indeed are quite toxic. The polychlorinated biphenyls are toxic and produce a syndrome which ve might call dioxinosls. However MONS 206556  YilHati*. ffwm inKrf itii.^M.-ctv^--^-Ytl >i|- the level! of Intake are much higher, several hundred fold to what we obaerved with the polychlorinated dibcnzoparadloxins. . DR- KIMBROUGH: I would like to add something to this. The work by Vos and his coworkers haa be-sn cited several times. These authors pointed out that they found hydroperlcardium which is the chickedema disease in the chickens that they fed with PCBs They found chlorinated dlbenzofurans as a contaminant in the European PCBs that thsy studied. They suggested that chickedema could also be produced by the chlorinated dlbenzofurans. DR. MERCER: Thank you for your contribution. That plus the diamines gives ua a real problem. Are there any other questional If not, thank you, DR. LINDSAY: Thank you, Dr. Mercsr. Dr. Kolbye, can you tell us a little bit about the Bureau of Foodal DR, KOLBYE: I will comment briefly and then act as M. C. for some of the othar ataff. < I woulk like Mr. Les Ramsey if we can get the projector to work to put on the screen some of the residue data to give you a quick Idea of what we have found in certain food sampling. Then I would like to ask Mr. Cook if he has anyting further to add to the chemistry and then ask Dr. Kraybill to tell us what are some of the gaps in our toxicological research. Les, why don't you come up and Just give a runthrough on these? MONS 206557 '*9 - MR. RAMSEY: The film looked as If It would not be visible to most of you. Perhaps I can summarize it, although trying to suomarize residue data orally is not very satisfactory. 'Vhat I 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. He have looked for PCBs in all the samples that we screened for pesticide residues. In our pesticide surveillance and enforcement program every sample that is analyzed there is also screened at the same time by the multi-residue method for PCBs. Zn this program in the past year we looked at 570 samples of fish. 315 of those samples ware positive for PCB. The overall average la of the order of 2-to-3 parts per million, in other words, the fish that we analyzed, at least, do not run as high in PCB as the fish do in total DDT, that is, DDT plus DDE plus DDD. He have analyzed 1,193 samples of cheese and found 8l positive. The highest level was 1 part per million, and the average about 3/10tha of a part per million. He have screened 805 samples of milk. Of those, 60 were positive end were identified with the contamination incidents that you have already had described for you in the Heat Virginia area, in the State of Ohio, and I believe in' 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 Hest Virginia incident that Mr. Duggan described, HONS 206558 where the transformer fluid was apparently used as a solvent for herbicides uied to control weeds on the right-of-way 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 arising from the pasturing of land that had PCBs sprayed on it for one reason or another. 317 samples of shell eggs were looked at. Eighteen of those were positive for PCB. The highest level found was 5/10tha of a part per million. The average, of course, is much lower. We have found traces of PCB in the byproduct from two potato-processing plants. One was In the Denver District and the other in the Seattle District. The waste coming from those plants showed traces of PCB. And so far as I know we have not yet been able to Identify the cause of the PCB in the waste. We have looked at a number of oysters. And, Incidentally, oysters, by and large, do not hsve high levels of PCB, at least the one* we have looked at. The total shown here in this table is 12, but I 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 th~ oyster, - We have looked at some miscellaneous foods. One sample of cat food showed 6 parts per million of PCB. HONS 206559 51 A sample of crab meat showed 7/lOths of a part per million. We even analyzed Che coating that was used on one of these silos Involved In Che milk contamination, and the coating contained 11 parts pf*r million. We looked at a sample of wheat, and It had 3/lOths of a part per million, while one of straw had 3/10ths also. These are a limited number of samples, from which I think it Is impossible to draw any firm and reliable conclusions. We have also, of course, begun Co 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 0.05 psrts per million. In three market baskets we found Che meat, fish, and poultry to coi.tain PCB. Again, the highest level was about a tenth of a-part par million. We also found'one sugar composite positive, which includes i candy. Incidentally. And we Chink probably Che 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 0.15 of a part per million. Also, we have found two instances where the cereal products composite contslned PCB. And in one instance this was traced back M0NS 206560 52 to the shredded wheat in that composite, which was picking up PCB from the container that had been fabricated from waste paper. More recently we have looked at some waste psper 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 those were positive. DR. K0LBYE: Are there any questions directed to Hr. Ramsey? fthis. 1 might add one note. Lea, 1 am not sure you mentioned So far we have not reported the residue of PCB in fresh frulta and vegetables. MR. RAMSEY: 1 should have said that we have not found it. DR. BOOTH; I would like to ask a question regarding the PCB levela in ahredded 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 case of shredded wheat. 1 was wondering Jf plants can take up PCBs. We do know that. In the literature, it is indicated that plants do tske up &DT. HONS 206561 SKW_D__U__ --wr "*' USdiS fihV 53 - DR. KOLBYE: I can't speak for that specific point. I don't know about the translocation of it. I would presume it can oci'.ur, 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, we find some 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 he hsve found recently in the case of DDT -- which chemically mimics PCBs in many ways -- that the closer the material is to the surface, the greater the contamination in the plant from volatility. There la the possibility of 7CB residues in soils giving rise to residues in plants, but depending on many environmental factors. DR. KOLBYE: I might add that 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 Nat.onal Cash Register Company paper but apparently there is not for PCB in the paper that is already marketed and recycled so 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. m i a L l a i i r f i r ^ ^ n r ---------- `TWFl'ri1-1 T HONS 206562 54 " Bill Cook, do you have anything further that you would care to add on the chemistry? . MR. COOK: I have little to add but I thought I might address myself to a question that Dr. l.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 PCBs, 1254 and 1260 appear with the pesticides through the analytical procedure. When we do find PCB we separate them from pesticides. 1254 and 1260 are very easy to separate. We also have confirmation tests. These Aroclors are very stable to alkali, for Instance, and we go through sn alkali test. Many of the pesticides such as DDT are easily altered by alkali. Besides that when there is a question one can use mass spectrometry. We don't do that routinely. A number of people have spoken about quantities. I think it is Important to recognize that there are some problems of quanti- talion, means of making calculations. Generally speaking, in fish the identity of PCB appears to be 1254 or 1260. Those chromatograms do not look exactly like the chromatograms obtained from standards. We make a comparison of all of the area under the curve from a standard against all of the area un `er the unkhown 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 peaks. 1 know one individual who makes his calculations based on DDE as a reference. These different means of bacing calcu- MONS 206563 +A. .|e-;wun*WM..sj|n'sijimem'iwww|||`i|iyiijL,|"i>w1'1 .in > i ' f ,.w--*- uw'm""** r 55 lations 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, Fora 1040ES was 4.5 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 wastepaper; this may contain forms containing PCB and thus continue to add PCB to the cycle. We have not done any work on the penetration of PCBs into plants but 1 would guess 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 plants. We in our lab have dona a little work on the effect of ultraviolet light. This is a rough treatment. We knock some of the chlorines off; 1254 appears to become lesser chlorinated. These results have yet given us any concern because generally speaking everybody throughout the world is reporting in wildlife residues which look like 1254 and H not residues with less chlorine like 1242. 4s MONS 206564 <l*' u-u - ' If there are any questions I will try to answer them. DR. MORRIS: I recall that during Che early days of the Food Additive Amendment we received food additive petitions covering the use of polychlorinated aromatics at indirect food additlvea. Did these early petitions include Monsanto's PCtJs, 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; Yea. It la allowed in a food packaging adhesive on the basis that there la no migration into the food. MR. COOK; When we speak of aroclora we are speaking of a mixture of chlorinated biphenyls, a mixture of chlorinated biphenyla and terphenyls or chlorinated terphenyls. The 4400 series is a mixture of the terphenyls and biphenyls, and the 5400 series are the terphenyls. Those higher ones are solids that seem to be very inert. The lower series auch as the 1221, the 21 percent chlorine is even water soluble. it la very fluid. . DR. HALEY; They also will produce chemical necrosis la they get into the skin, the terphenyls. So they are 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? MONS 206565 -------- -------------- " -- T iiH ftftr*^ii< irn ta lrfir^riii r i itiM at^iriiTair-- im in n a frfb K m u ^ ^ iiiiiin ii k > *m y id g ttL i_ L i I think the point about the terphenyla ia that as far as we know there is no migration. This can be checked. I think it would be Interesting if the Food and Drug Administration could declare the Form 1040 a hazard to health but I am not sure it would be appreciated by the IRS. DR. KRAYB1LL: Dr. Lindsay has indicated to you that the status reports that we prepared, there are two of them -- the last 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 ia a good thing since such information is most illuminating. Another thought that came to my mind was the similarities in other areas of work such as research on the dioxons and some of the pesticides, in dloxon toxicology wc encountered the problem of chloracne in occupational exposure and this morning a PCB toxic response was mentioned that la hydroperxcardlum. One may have aome contaminants here as one observes with the dioxins. The polychlorinated biphenyls contaminants occurring together with thoae from dioxins. If one looks over the various reports -- and there ia an excellent Swedish report aa veil as 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 a little more on the safety or the toxicity of these particular compounds. ' One thing we should identify are.the primary constituents MONS 206566 inSftettr.i' r-n reTiffiV m Kii irid'fumi-.. ')8 of the residues of PCB. This la a big talk. Of the 1,200 series, 427. and 685i and 607. chlorine compounds and so forth, fish, perhaps, s a food vould be a good item to survey in this identification. It would be helpful to know what chemical or molecular species we are dealing with which would help us in making our assessment 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. I sure would like to see this data. There is some PCB water data, perhaps on potable water supply. There may be some PCB levels determined in the water in the estuaries where the fish swim around. We should have auch data. Mr. Ramsey previously reported the data on foods and food composites in the diet. A statement was made about fruits and vegetables as 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 insofar as total Intake of our diet. Another important aspect is that of human monitoring and Dr. Hcumcr and Mr. Burse 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 Is most interesting to have such data but X wonder perhaps if one should not acquire data from surveillance MONS 206567 y'SJ.H wj !. mss .-tn-H.1 '*. . rysihip. l ' i-..t across the country to see whether there are any geographic differences, EPA has the monitoring system to do this. EPA has the resources available In about 15 conmunlty 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 Lhink we should study the effect of these Aroclors on certain human cell cultures. Insofar as toxicity is concerned, in short term toxicity the response that is most intriguing to me la the effect on the liver microsomal enzymes affected by the Aroclors. An effect on the liver microsomal enzymes by the Aroclor^ one might study farther, since this haa been done to a certain degree. The influence of dilantin and hexobarbital, which interact with some of the pesticide compounds, have been explored such as DDT and dieldrin and lindane and compounds of that type as well as carbon tetrachloride. Theae have an Important effect Insofar as synergism in their interaction, therefore how much do they potentiate, which could have an analogoua situation in real life. Another area ia the teratogenic study on the Aroclors with certain teat syatema, other than the chick embroyo, FDA has done extensive work on a wide series of Aroclors with the chick embryo and reported a host of biological defects from these various Aroclors. Another area Jar study is the short term reproduction response, the effect on the fetus. This is most important. Last but not least -- there should be some work taking place on the mutagenic effect of these compounds. Then Mr. Burse and Dr. Hairaner referred to HONS 206568 .Che metabolic studies and here we need a better idea 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 i metabolites -- such as DDE, DDA and DDD- In truth then what is the toxicity of these various metabolites? Now we get into the long-term effects of these compounds and we immediately think of the carcinogenic properties of these compounds and 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 sites such aa the kidney, the liver, the brain, et cetera. Experlmenta in chickens and rodents do not follow a characteristic pattern Insofar as reproduction. For example, the Aroclors seemed to be more toxic than DDT in these particular studies. I made an outline here that you may want to consider on what 1 called disslmllarltlea in PCB and 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 microtome enzymes. To me this is most Important. - B. The reproduction experiments in the rodents and chickens which 1 alluded to* where I said the aroclors may appear to be more toxic than DDT. H ] MONS 206569 tyMVP'Vfl'TC- T** 61 C. The metabolites apparently are unknown aa is 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. Hanr>er, 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 is in the test work with Aroclor 1221, 1248 and 1268, administered at a dose level of 50 parts 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-pcrcent 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 suimnarized 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 ro Dr. Kraybill? DR. MORRIS: In light of the relatively small quantity of IJBs now being manufactured, it la 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 back over three decades. Do we really know how much PCB is now being produced? HONS 206570 J .< 4 r if ^ riinf*^' Afc^^c--- **- 62 Are there large source* other than Monsanto? The reported universal occurrence of residues Indicates there may be sources which are currently unknown to us. . ,, DR. KOLBYE: I don't think Monsanto has ever released data on what the volume of their previous production was. DR. MORRIS: 1 understand we have made some pretty good . estimates. . DR. KOLBYE: That may be. Who has the information to speak 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 viawpoint, axcept perhaps for the suggestion that after the meeting today winds up and Is concluded I would like to suggest that we have some sort of a continuing panel of representatives so that we can exchange infor* mation. DR. KIMBROUGH: I would like to point out again that I do not want to maka tha statement that the PCBs are 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 PCBa. I wonder if chloracne has been observed recently? Do the workers who worked with the flslimeal 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. HONS 206571 A ~-- -- ---------------- 63 DR. NELSON; The Japanese do report that the poisoned show ths colored individuals did have skin disorders. DR. WORF; I would like to direct a question to Mr. Duggan, 1 would like to know whether the cortamlnated fishmeal is going to be disposed of in any regulated manner. What are the plana? MR. DUGGAN: The contaminated fishmeal, of which there la now between 1,000 and 1,500 tons, la 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 as fertilizer. DR. K0LBYE: Fertilizer for non-food crops? MR. DUGGAN;- Are you going to enforce that? DR. K0LBYE; No. I guess that la our hope. MR, DUGGAN; On thla fishmeal, in our Initial investigation we did look for PCBs 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 the responsibility for all products going Into the home, particularly thqse that are accessible to children. Recently, we have begun a project to investigate if PCBs are included in the plastics, particularly in children'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 206572 I 1 64 Certainly all sources should be looked at as part of the total picture in terns 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 7CB research. Dr. Hoopingarner and others will be heard. Then we will come down to the crunch; where do we go from here? As to lunch,.1 think the only advice 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. He 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 aeme day.) . HONS 206573 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. Duncan, I think we have reached about the point where since I think you know the gentleman involved in other agencies better than I do, will you Introduce any individual here from either Interior or NOAA, and ask them to give a situation report. 1 MR. DUGGAN: The last PCB meeting we had was held out at Patuxent, hosted by Dr. Dustman and Dr. Stickel. 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, ladies and gentlemen, vc have been familiar with PCBs for a very long while. In the very early stage we didn't know what they were. The eagles told us that they were there. We learned very early in our chemical meanderings to stay shy of them, and de veloped methodology at Patuxent that allowed us to split then off, so to spe. We did this by zoning, 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 Stickel, who is our environmental pollution research coordinator, and you will be hearing a litt! 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 JAQAC in May), I believe; and Mr. Heath, who is our Center biometrician, and also in charge of our toxicology work. He has carried on : number of tests, short term toxicity tests, using our standard test species, and also longer term tests, studying the effects of PCBs on reproduction. HONS 206574 66 . We have as of last March a publication that is soon to aake 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, I would like to read a summary of this paper, some of which is well known to you; some I hope will be of such recent origin that it will be new knowledge. This paper is a review of the litera ture: there have been several other reviews mentioned here 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. There are several things here in the sunmary that I think you will find of interest. 1 am sure you are all aware that foreign scientists have given a fal amount of attention to PCBs, and I would like to start by mentioning that special studies in the Netherlands, and Great Britain, as well as in the United States, have tra.ced PCBs to Industrial effluents, although other possible sources have not been followed. The use of PCBs 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 are higher in animals living near industrial sites. PCBs build up in biological food chains with increases of tens to thousands of times from lower to higher organisms. This is of very great importance to those of us who are concerned with environmental effects. HONS 206575 67 " Experimental studies have shown that PCBs have a toxicity to mallards, pheasants, bobvhite quail, Coturnlx quail, redwing blackbirds, starlings, cowbird? and grackles that Is of the sane order of toxicity as DDE to t*iese 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 Coturnlx 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, we have heard of the PCBs of foreign manufacture containing contaminants to an extent that greatly increased their toxicity. So we have contaminants that are contaminating the environmental contaminants, 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. PCS6 enhance the toxicity of Dieldrir. and DDT to Insects. Residues of PCBs In the brains of birds killed by these compounds measure In the hundreds of parts per million. PCBs may.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 affecte 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 206576 significant differences 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 cf Arodor 12M, and by low doses of Aroclor 1252. With these few remarks, I would like to ask Dr. Stickel 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 studlea of PCBs. DR. STICKEL: tfany of the' principal findings Dr. Dustman has al ready covered. I think maybe the main point of our work that would be of concern to you ia 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 analyzed at our Center from the time we got the first gas chromatograph. And the ones that have been collected and analyzed 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 wer' 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 " m m m * m " ^ * * m * + * w wM w>" i i u n i w i j u j # HONS 206577 \ ) 1: ;j \t 69 In a number of areas along the Atlantic Coast. Connecticut osprey eggs contained an average of 16 parts per rillllon PCBs, with amounts ranging from 7 to 30 parts per million. Eagle eggs had an average o:r 10 parts per million of PCBr and even In Alaska, 1.65 parts per millloM. Ospreys eat nothing but fish and the fish haven't been through the processing plants to be directly contaminated by leaking heat exchanges. 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 feeds 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 sane soils where we are growing our crops, and again, these birds are a product of the same food base that we depend upon. We 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. The really Important part of our work, however. Is not so much the MONS 206578 r distribution of PCBs In the environment and the levels of residues thit are encountered, but the significance of these residues, Mr, Heath in conducting research to determine the effects of the various formulations of PCBs on the reproduction of birds, and on their survival. The PCBs follow the standard dose-response relationships thit 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 all 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 are sensitive to these two materials may be somewhat different, however. For example, bobwhite quail and pheasants are birds that are not susceptible to DDE-induced shell thinning except in a very minor degree. Their shells can be thinned by massive doses. But, whereas mallard ducks are sensitive to DDE, the opposite may well be true with PCBs. Mr. Heath's studies showed no reproductive effects of PCBs on mallard ducks at anything that would approach a realistic envir onmental level. In contrast, the Monsanto Chemical Company's studies with chickens did show shell thinning as a result of dosage with certain PCBs. This has not been pursued sufficiently yet to be sure, because all the formulations have not been tested against ducks and chickens at the same dosages; the cross-comparisons s.e 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 1 j PCBs, determination of the tissues to analyze, and the critical residue .i i HONS 206579 l -- iiV ittrhni^iiH togrm r i i w i ^ n i i a rw iiri f llim it f if* mu i -- ii ii rn M -y -friftif ' , ^g ^ftia in itir^h i ,v ~ -~T ------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 IS 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 PCBs. Mr. Bagly has made studies of the metabolic changes of PCBs in quail and these results are nearly ready for publication. An Important problem In chemical analysis was brought out thi6 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 term 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 Karine Environment," w.hich is a National Academy of Sciences publication that includes a discussion of PCBs. HONS 206580 jj.i . i ' >' ji p. fm"- 'H' 72 MR. DUGGAN: Since neither Doctors Dustman nor Stlckel 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 wHt the sources of polychlorinated hydrocarbons are In the marine environment and is'it possible that some of the sources might be from ships that have sunk that have used tons -- lit erally tons of PCBs 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. 1 would suggest that as a possibility. DR. ST1CKEL: There Is a possibility; however* quite a bit of work is being done in England and they have managed to trace PCBs to the scwsge outfalls from Industrial plants. This material has been taken and 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. Hammer, EPA. I just wanted to clarify* did you say that woodcocks had the 49 i parts of the PCBs, or the earthworms? DR. JTXCKEL: Four to nine. DR. HAMMER: Is that in the woodcocks or In the worms? DR. STICKEL: On the woodcock breast muscle. DR. HAMMER: What waa In the earthworms, do you know? DR. STICKEt: No. MQNS 206581 - -TrliHiifc'fW 11 it fcV 73 DR. LINDSAY: Are there any other questions? - If not, we have Mr. Tom Carver, and Dr. Ebieraon, and 1 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 ssked us to corne as observers, and we can best do that by sitting down, The Service rather abruptly terminated Its 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 prograi has been looking for PCBs in shellfish at about 170 locations around the country. This program is also conducted at Tom's laboratory in Culf 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 came 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 indict curlier this morning, we asked agencies as we contacted them if they wished - - -- *- ~^ i--Brii - ~ MmafmeHist i - 1~-- M HONS 206582 74 to bring in someone from outside the agency that was either working under their funding or about whom they know and what they thought should be here. W* brought two people in. Their names both begin with "H" so, if T go alp labetically, I 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 us a little about that -- and anything else? DR. HARRIS: Thank you Mr. Chairman. Ue became Interested in Aroclor when the inspection service began to pick up residues in poultry meat, after the New York fiasco. Ue had some tests underway to determine the toxic effects on poultry. On June the 9th, 1971, a condition in two-week old broiler chickens with symptoms similar to chick edema disease as described by Schmittle and Sanger was seen. The most common symptoms were gasping and incoordination of the head and neck just prior to death. The most severely affected birds emitted a 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 hydroperieardiun 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 a roughened appearance resembling cirrhosis. The kidneys were swollen HONS 206583 and pale with small hemorrhages. Some of the birds had white ce*mjs-llke material, resembling a bacterial infection over the heart and the liver. There was inf lamination 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 crotalarla poisoning, a toxic substance in the feed was suspected. Feed from houses with affected 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 days of age, the chicks on the suspect feed were not very active and would huddle close to the source of heat. Feathers were ruffled 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 and lesions as we had observed. The North Carolina Department of HONS 206564 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 Hexachloride. 8,8 parts per million. Chick Edema Factor, negative. The principal toxic Ingredient in the feed was considered rr. 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 and the cause. We then notified the Depart ment of Agriculture, who has this in their jurisdiction. The gross pathology has been described in the literature by McCune, and we feel that based on his work, there is a synergistic effect between the benzene hexachloride 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 some went down to as low as five percent. We did some analysis of PCB on chicken embryos. These were 14 oneday old dead embryos. They contained .33 parts per million PCB. The yolk of fertile eggs contained .97 parts per million, and the fresh yolk material from egg6 prior to being placed In the incubator contained .29 parts per million. These were all from breeder flocks that experienced lowered hatchability. We are doing the hlstopathology on the sections collected from these birds, and we'll have reports op- this at a later date. 1 will be glad to entertain any questions that you might have regarding the problems we have in North Carolina. HONS 206585 ip-fV. i^i*rrfr*''r>*~ Tt 'V"7*7* ^ a J h a M ^ M --------------- --***i 77 ` DR. LINDSAY: Thank you. Dr, Harris. I think as Dr. Mercer 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. Hoopingarner from Michigan State University is a member of the tean that is working on the problem of mid-vest meat kill, and I'll leave it up to him to describe 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 beaches of Lake 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 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 poisocin That is, the people in fisheries, Dr. Howard Johnson, said that this appeare to be what was happening. So they undertook an extensive program In moni toring of the mortality of the young fish. .................- - . i f i r - - HONS 206586 78 Of course, prior to this tine they had also monitored the DDT or L'hlorinated pesticides within these fish and had found quite large quantities of DDT. In fact, so large thet most of the fish were not allowed to be.shipped lnter-atate. In the subsequent years since the first harvest of the fish, the young were still dying, but now the sympLonto logy had changed. This always looks like Monday morning quarterbacking, but essentially there was a 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 wlers 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 almost 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, and he fed pesticides to mink in very high quantities, higher than Tound 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, HONS 206587 -1254 and 1260, and fed it to min!.* They didn't fail to reproduce; they failed to live. This is vhere the research essentially la currently at Michigan State. . They are now beginning a new season feeding kits and leading up to a reproductive season, and we have initiated a cooperative program with fcur 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'm 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 Zablk is primarily Interested in the analytical chemistry aspects, but also in photo decomposition. My own personal interests are in the cytotoxicity to various cell cultures. We have a number of mammalian 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. KOLBYEt Dr. Kolbye. Have you observed any chromosomal defects? DR. HOOPINGAR.NER: 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 was a very short time -- like 60 days, and they were dead -- before they could reproduce. HONS 206588 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 pathalogical symptoms occurred prior to death aa I don't know. And the fact is, I think, to be honest with you, the death took them quite by surprise. They expected some inhibition of reproduction, but not death. DR. SENTI: What was 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 diacuaa their research, and particularly any part of that research that bears on the part 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 and 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 Aroclora, or PCBs; but I don't mean to preclude anyone from speaking to that point. HONS 206589 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 X don't know whether anybody today will want to speak to it or not, there is the area of needed legislation. I 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. I know that Congressman Ryan of New York has been very anxious to get rather sternly repressive measures on the PCBs. But I would like to throw this open to discussion. 1 think per haps just to begin with. If Dr. Dick Gordon as openers could outline some of the questions that need answering, and knowledge that needs to be galne: 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 we know that we should? How do we establish Investigative prlot itles? And, what are possible legislative and regulatory remedies? X thought of five "D's" and a "B" -- Danger, Degradation, Dlsposl 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 we only have a potential danger? The min experiment, for example, might be one of the few examples of acute mammalia 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 DDT et cetera. Therefore, the environmental degradation pathways need much greater elucidation. HONS 206590 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 PCS. 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 seme good thoughts that should be dis cussed further. There is the Draconian step of discontinuance. Monsanto, as 1 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 we 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 great 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. HONS 206591 D.MU ihfi.TUh-K.-i;^ j-- 83 We really want to think more about this. Man Is a social animal and reports dealing with minor changes in behavior patterns should be fol lowed up. We all know that small 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 well as exchange of information do we need? And what kind of prohibitions shall be requested or promulgated? Finally, can behavioral effects be used as very sensitive indicators? DR. LINDSAY: Any questions of Dr. Gordon? He was asking a ques tion of everybedy before he sat down. Dr. Kraybill, of course, had already summarized in quite succinct fashion many of the problems that are left unanswered by the knowledge that we have, and he has had admirable Insight into this as the compiler of the status reports that we 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 some you would like to make over? DR. KRAYBILL: We might comment further -- and I 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 for of these compounds and I am sure that through our chemical studies we'll be able to identify what specific chemical entity or what molecular species we are dealing with. HONS 206592 ^Ak mmxm; i nroi <* .-ms**r~c^r .--. /-.uc^z-M,-. - -MLtf^ ,^1-if -,.^| 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 the 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. I just wondered if there were any comments they might have to make other than the factthat, "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 aware of interactions. We are barely touching drug interactions, outside of an occasional report in the literature on drug pesticide interactions in humans -- I guess these were animal studies, laboratory studies. This is the extent of what we have gone beyond drugs. DR. LINDSAY: Well, ve trust you'll keep in touch with all of this now as it goes along. ' ` Dr. Thomas Haley is with us in the back of the room, and any fellow that has done as much pharmacological work as he has done has some comments, I an 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 6aid "sex"? iff*. 'P'-tq;. M.p wy ! HONS 206593 / / 85 ` DR. HALEY: Yes -- the difference between the male and the female -- (Laughter.) .. DR. HALEY: I 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 aminolevulinic acid cycle in the bone marrow is being effected. Thia may be effected primarily in the same way that lead does it. I think the ALA synthesis sivuild 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; I think I can speak loud enough. We have found with the dioxin problem that the level of dietary fat played a role in the toxic responses of chicks, that is when the level of dietary fat was high, we did not get as much of a toxic response as when we lowered the fat content, 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 I would suspect that perhaps the ahsorbability of the polychlorinated biphenyls could be facili tated in a similar manner. >l>mw V. 'j. ii i^i.i SUIT HONS 206594 ytl Ml m * -- null / / } ' V t' 1 .i h i J>r. Harris mentioned & while ago 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 are really dying in a stage of malnutrition -- in addition Lo other toxic responses at the enzyme or subcellular 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 last fall, that the absorbability of the dioxins were related to chlorine content. Again this may be a factor to be studied with respect to FCBs. 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 vent on here today, and what might succeed It? DR. BURGER: .Dr. Lindsay, first of all, thank you very much. Let mo just take the opportunity of offering my congratualtions to you for - and tha Food and Drug Adminlatratlon 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 n scientific matter that impinges upon the public policy machinery. 1 ` HONS 206595 87 believe, Incidentally that our place In life, as someone described It, is the marriage or estrangement between the scientific community and the public policy making machinery. But think that indeed this is representative of a matter which is at the crossroads of some public policy decisions. Let me just ex plore a couple of these with you, because 1 think they are terribly im portant. It seems to me that if one were to summarize 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 composition, and following from that, the biological availability to various species in the environment. I think these are all matters which illustrate in part 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 is involved? Perhaps 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 MONS 206596 * ( i. 3i I i : t ( i 88 environment. This then raises series of eldltlonal points such as the responsibilities of the private and public sectors to do the research from vhlch Information Is used to make decisions, the question of re sponsibility of divulging Information ahvut 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 list) there is the matter of the responsibilities of the public and private sector for controlling the distribution and regulating the production of a material which is either implied or known to be of some concern or even hazardous. If I were to back 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, and 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. 1 feci there is a piece of legislation now pending. The Toxic Substances Bill indeed was written in part I think to address some of these very questions. Fourthly, I 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 cnador than it has perhaps in several years. 1 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 206597 4 i -!* m mm w n. 89 In a better 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 is really, I suppose, mo,,t 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 length. Thank you very much. DR. LINDSAY: Any question of Dr. Burger? Ve 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 say 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 c the past three days, in the first of two sets of hearing. HONS 206598 T" Basically what I want to do It Just quickly outline some of the provisions in the Act to show what is envisioned as a possible mode 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. It further provides for the establishment of test protocols and testing standards for all new chemicals being produced in commercial quantities. As Dr. Burger has indicated, one of the real needs in this area is Information dissemination. The bill provides for full disclosure of manufacturing data with appropriate provisions for proprietary Information. It will create a chemical compound classification system, and information storage system, to handle the kind of information that we have brought together today. As some of the speakers have mentioned today, there exists simi larities between dloxona and PCBs that should be noted. It Is possible analysis of these chemical similarities could lead us to suspect other classes or other types of compounds that might cause 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 is hoped that we will be in a better position to prevent adverse effects from new chemicals prior to their release into the environment in large quantities. HONS 206599 y .1 i - 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 will 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. Flshbein, would you have eny comments from a sister agency t HEW7 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 is the extent of our Involvement. DR. LINDSAY: For those of you who couldn't hear, Dr. Flshbein suid 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, I think we have come down to the gentlema: 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 206600 92 Dr. Norton Nelson at 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 memb ;r 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 I can remember. 1 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 I 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, we would love to hear what you have to say. DR, NELSON: Thank you. Dale. Dr. Lindsay has opened up prospects which 1 am hot 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 the discussion. On the other hand, 1 perhaps perceive -- 1 am not sure 1 am right here or wholly fair -- a sort of midafternoon 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 206601 93 . Realistically) however, I 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, we do not know the total production or use of PCBs 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, t 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 chijf environmental sources of PCBs. It is true that in several of the episodes the difficulty stemmed from accidents - thus, the misuse as herbicide in West Virginia, the leaky pasturlxlng equipment in the fish processing, the defective meat transfer units that produced the Yusho disease in Japan. These might give us the reassurance that we are dealing only with such acci dents. Z 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, 1 sus pect that the wide spread environmental contamination may arise from continuing losses perhaps contriouted 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 are. " . HONS 206602 ^v^lk&ri'ir 1'^ itlitff Ifil- V fi I iWk rffi HTfJhrmfrw mWir-.* *.......- 94 Again, I believe we have only very crude Ideas as to the patterns tf movement of the FCBs 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. I 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 FCBs or PCB containing materials. I suspect that there are not more than three or four incinerators In this country that are capsble of successfully disposing of PCBs. In fact, I 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 circumstance, and if I am wrong please correct me, that the present interim guidelines, which the FDA has established, were 'it 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. HONS 206603 95 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 sized by the work at Michigan State on the minks. That work Is 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 1 suspect that the gross trends we now per ceive will be sustained by more refined work, my confidence doesn't carry me to the point where I feel we 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 dibenzofurans 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. i DR. LINDSAY: Thank you, Dr. Nelson. Are there any other contributions that the afternoon somnolence will let you make? Dr. Harris? HONS 206604 96 DR. HARRIS: There Is some evidence, T helleve, for certainly particulate explosion in the cities and this would fall out into the dust end dirt. I don't know if it would get into the food chain. DR. LINDSAY: Dr. Kolbye? DR. KOLBYE: I 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 at this meeting, please. DR. LINDSAY: Any response to Dr. Kolbye's question right now? Dr. Dustman? DR. DUSTMAN: I think it was about two years ago, if my memory serves me correctly, that a small group of individuals met in Duluth, Minnesota, for the purpose of exploring where we stood with PCBe 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, and it started out to be just a few individuals who were Interested that were going to get together for the purpose of seeing what we knew. And it grew into a full-blown meeting at which time quite a few university people were rep resented an', a 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 at irregular Intervals as the attainment of new information would dictate. And I have before me one such newsletter. HONS 206605 97 There have been three of these. They cover all 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 .$ 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. Kolybe7 DR. KOLBYE: I think that is an excellent suggestion, and I 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. I had invited Dr. Mlder here today but he had other priorities and wasn't able to come. I can't speak for the NLM but I would think that Dr. Kissman'a group In the Toxicology Informa tion Program would be very much interested in participating. I 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 beck to your agencies to alert your agencies to this need, MONS 206606 98 particularly If you balieve In It, and then some effort may be made on the part of the lndlvlduala for whotr each of us work as to some decision regarding such a committee. For example, something similar to the committee set up be tween Interior, Agriculture, and HEW w*th regard to the nitrite program. Dr* Leo Friedman Is chairing that ,,and he la not here to report on It. Sut that sort of thing I think Is very valuable, and something like that could come out of this, Al, If that Is what you had In mind. But I think probably we have the wrong people here to designate the Individuals although we may feel to the contrary. VOICE: I think we need both* s committee to coordinate among the agency resources and I think you need a superb toxicology and residue information program that can be disseminated broadly. DR. LINDSAY: No argument. Dr. Worf7 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? I alluded earlier that I used to work In an Allis-Chalmers plant chat 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 ;im sura that NCR, National Cash Register, their use of PCBs In paper and so forth, there la 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. I am not aware of more recent work which would relate to more modern pat terns. They are probably very poor. HONS 206607 f i' T 'i l 99 - " Maybe Dr. Hammer can respond to this. My feeling Is that there may be data there, but I do not have It and I cannot ssy 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 skin disorders and the problem of liver, acute liver diseases, et cetera. There was virtually nothing available from the occupational health literature, and 1 think the prob lem that those of us that are concerned with human health problems are having now with many of the toxic substances is that the kinds of ex posures one saw in industry were really 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 effects. DR. LINDSAY: Dr. Cranmer? DR. CRAMER: As 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 comments with respect to the problems of the Environ mental Protection Agency. Dr. Hammer has Just spoken about occupational exposure. Cer tainly if we had some information on the effects of occupational exposures to humans we would have information which would perhaps be of use for predicting the chronic effects of acute exposure or acute effects of acute exposure. HONS 206608 m pi My T 100 However, I would hasten to add that we really should Increase the surveillance of the general population, because the general popula tion and occupationally exposed are not exposed to .the same compounds in the saae relative amounts. . We have discussed several times here the fset that we have a biological modification of these compounds. Therefore, when you eat coho salmon or chickens you are not getting the same profile of compounds as 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, we ususlly utilize analytical grade materials that are going to be analyzed by gas chromatography. What we should be * doing is feeding animals the material which humans would be eating. i 1 would also say that what we really want to do is measure the total Impact, and we really need, that is the Environmental Protection Agency needs, to follow the routes through the environment and test representative organisms along the way. For example, we brought up the problem of disposal 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 I : be said for research into ranges of sensitivities mediated by age, sex, interactions and genetic differences. : i HONS 206609 101 1- ^ We are dealing with 200 million people, we set up the better experiments with a few hundred animals The sensitivities of species are variable, just as are the ages. The difference in toxicity of PCB to the mink and rat are, enormous. Certainly the weanling rat is more susceptible to the Induction of mlcrosimal 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 that polychlorinated biphenyls alter many of these actions. I would say 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 la I had asked Dr. Gordon to make some statements, and then overlooked him on the list that I had. The other one was that I had tried to, on several occasions, reach Dr. Raymond Moore, who la now in the Institute of Occupational Safety and Health, to get him here today, and failing in those two or 1 three times, I am afraid I lost track of It and I did not follow through. So that la why we do not have him here, or someone from Occupa- t i tional Safety and Health. ' Dick? : DR. GORDON: I have the same kind of feeling that Dr. Nelson was , developing at lunch, that today is sort of an opening warmup meeting and it r ----- y -- * - HONS 206610 102 could very well be that after circulating the papers, thinking, looking at the transaction, maybe reading the newsletter, we might want to sched ule a 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 I 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 there 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 I feel that that might be an appropriate thing to consider doing in three to alx 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 a while ago that they would be Interested in human toxicity data. In the library yesterday I came across an article in one of the recent bulletins of environmental contamination and toxicology. There was a 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 there were three deaths that had occurred from PCBb, 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? in f illnii r fe j- f*11ij HONS 206611 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. Now this Is again a bird, su I would suggest that might 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- , tlon hazard from these compounds. We are talking about incineration, where this will be disseminated out and be in the atmosphere for people ( to breathe. I am 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. 3i I would suggest a full scale program on the Inhalation toxicology of the PCBa be undertaken. DR. LINDSAY: EPA, take note. Dr. Hammer, you said you had gotten some out of the particu late sampling from the airt too. DR* HAMMER: I would like to tell my own experience the past 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 and ability and sometimes even reading what each other writes or calling each other on the phone, that one pla.e where one really docs have a need for a multidisciplinary approach is in the trace or toxic substances, metals, synthetic organic materials, pesti cides. And I 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. HONS 206612 104 I think that although there is a lot more Information that needs to be done, that there are already 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 ie that EPA recently published a summary 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 and studied a single geographic area. In this case there vas a source, a smelter. And in addition to the gaseous pollution they studied several heavy metals, and many of us who were there were studying people and the environment animals. Whatever it is, I think ve ought to consider when we plan our new studies to see if we can perhaps do our studies in the same place or in similar places, at least, and so 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 sane answers to these questions rather than getting off in different directions again. DR. LINDSAY: Dr. Morris? DR. MORRIS: Murrell Morris, Food jnd Drug Administration. Many of us here have suggested that we have several more years of research before we know what to do about the PCBs. One speaker dis cussed the proposed 'hew legislation on toxic chemicals. May I suggest that, under our present Food Additive Amendment, either Mr. Les Ramsey - ------------- ibujfc. J ii iiifim i i i i a i^ r i------ -- --------- wri t'tv .7JP "t*,' HONS 206613 mam 105 oV Mr, Reo Duggan could, by tomorrow morning, draft a regulation which would eliminate the use of PCBs In food plants und feed mills, the latter being the principal known route of entry into our food chain. Rather than quote the law, a copy of which I have before me, I will present It in simple words. The Food Additive Amendment vai. specifically designed and enacted to prevent unsafe levels of non-food substances from getting into foods, either by direct addition or Indirectly by what is commonly referred to as 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 been reported here and elsewhere that PCBs are currently being used as heat exchange fluids In feed mills, snd that this "intended use results, indirectly, in it becoming a component of food." Since it Is a non-food substance which is not generally recognized as 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 is 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, i.e., before we had the facts which have come to our attention as a result of this conference.i i MOHS 206614 DR. LINDSAY: Reo Is not here, and Las la. I know what Reo would say first, "Could you enforce It If you had It?" Dr. Krayblll? DR. KRAYBILL: I detect from looking at the toxicity data that there Is some disparity In our findings. Sane of us have discerned these differences. Again, I hate to reiterate our whole experience with the dioxins on Identification and establishment of purity and I 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 s 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, we ran profiles or we at least Identified the type of compound we were working with as standards. This might be a useful suggestion to these Investigators here. If they get together and Indicate what type of Aroclor 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, 2,3,7,8 symmetrical tetra which you will normally get If you produce 2,4,5-T from trichlorophenols. That Is tT.e 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 ore far, far leas toxic than that, by a factor of 2,000. HONS 206615 107 Ve do not know whether we might run Into wide variation In toxicity In the group of compounda that mke up the large number of polychlorinated biphenyls. You would have to separate out each member of the aeries and test for toxicity. There may be a situation similar to toxaphene. There are 50 to 100 different chlorinated compounda In s toxaphene that are closely related chemically. In producing toxaphene, the percent of chlorination Is extremely Important. When chlorinated up to SO percent, for Instance, the material Is not very toxic. When chlorination Is in the range of 67 to 69 percent the product Is a highly toxic Insecticide. Over 69 percent chlorination there Is a rapid fall off in toxicity. Now back to the chlorinated biphenyls, theoretically there are 210 possibilities for different Isomers. There sre people who are separating these and my hois Is that somebody will do some Individual Isomer toxicity testing, which I think would be very important. I think this would add a good deal to our Information. All these different . .. Isomers are not present In the different Aroclor products. Arochlor 1242 will have a number of compounds In cotnnon with 1254. I don't . . . .. * think 1221 has much In common 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, wc would be a step ahead. DR. LINDSAY Thank you. ` ` Lk. LINDSAYj Dr. Riley? DR. RILEY; Dr. Riley, CSRS, Department of Agriculture. I haven't heard the question brought up today, and perhaps it ought Co he considered, what are the alternatives to the PCBs. HONS 206616 ` 10* liov, it came out during our discussion of these hut exchange fluids that there ars son expansive materials that can he used la pro* cessing plants. Do ve have good Information In this aru as to alternate materials, substitutes for FCIe and what thetr cut would hot What are the long-term projection for when alternate materials cam he brought Into uset The lndlcatlona that ye aeea to he getting In thla conference. and vhat ve are hearing from people who ere working with these materials are that thla Is an extremely persistent chemical* and it is going to ha in tha environment for a considerable period of time* Thank you* DR. LINDSAY* Thank you. . Dr. Plinmart DR. FLIMKER: Dr. Fllaaar. ARS. V.S. Department of Agriculture. I would Ilka to draw your attention to one point in the Monsanto technical bulletin on aroclors. Thla follows up Dr. Cooks' cenit. For nearly every Aroclor mentioned, a darkar. leas pure variety exists with aboht tha same physical and chemical characteristics, hut lower in price. So I think that somehow. our toxleologlcal study should ha related to these two grades. ; Ve talked to Monsanto about tha dangers of oxygenation in the higher grade a- oclora to give dlbenzefureas, hut ve don't know anything nbouc the lower grade aroclors. what their degree of purity la and whether they could contain dlbensofurana. This la one point. Tha second point 1 would like to emphasise Is that for thesa In vestigations. and X don't know whether thalr synchsale is currently being HONS 206617 109 attmapted. but we need come radloactively labeled aroclore If we are going co follow the environmental fate of these compounds. DR. LINDSAY: Thank you. Dr. Plltmoer. , Anyone else? Dr. Hooplngarner. DR. HOOPIXGARNEfc: This la a comment I would like to direct, maybe at the Patuxent group. They said that they have seen polychlorinated biphenyls 6lnce 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 who hts not been close 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. Flick? DR. FLICK: I-would like to just mention once more, and that Is again drawing on the dioxin problem of the pastr perhaps still current. Is the setting up of a long term study with a view to determine If after exgpaure, ** there actual recovery. Now we had -- we did this with the dlffxlnes In a short term study and wc found that after removal of the 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 -- c DR. LINDSAY: You mean of the ones that have been continuously exposed? HONS 206618 no DR. FLICK: Yes -- and they were compared with controls that were continued on dioxins. So this type of approach perhaps could also be carried over to PCBs to find out If lnde.id 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. KARRIS: I would like to say a few words. Dr. Cordon proposed one question. Is there a clear and present danger? I don't believe that has been resolved. We are going back and doing s lot more pharmacology and toxicology on this, and it might be another year before we gain more knowledge. Ue 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 it; they are completely Ignorant of the hazardous material they are dealing with. They knew of the leakage, and Monsanto knew lc that is why they continued to ship store and more In, without any precautions. So I believe we have a present and clear danger. Time won't 'v wait until you can generate a year's toxicology. DR. LINDSAY: True. DR. KimbroughJ HONS 206619 n pj f piw w w iii iip p iip t i i iJKi im m .. ........ H Jf 111 - ' OR. KIMBROUGH: T wonder IF there would be any point in doing some liver function studies and some other studios In the workers that have been working In the fishmeal processing plsnt, and whether this could be doue 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 G1 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 suit against themselves later on. DR. HARRIS; This Is owned by the Peruvians. They have a dif ferent ballgame. DR. LINDSAY: They would probably load up some of our shrimp boats down there. Are there any other questions? A little while ago Dr. Burger was very generous with his comments to me personally, and I am very much afraid mistakenly, becuase I don't deserve any compliments here; you do - the people who came. We set this up In a big hurry, and everyone who has contributed bo generously of his time and thoughts to the conference deserves the compliments that Dr. Burger passed on to me, and I'm sure he doesn't mind me giving them to you on his behailf. . ' T certainly appreciate you having come today. I hope that more will come from this meeting, that individual sessions tailored to the particular talents and problems will emerge, and that from this we'll sll be better off. Thsnk you very much for coming. (Whereupon, at 3:30 p.m., August 5, 1971, the conference was concluded.) HONS 206620 p i.M J il VyiM