Document Kg8MOaDQeNy0eoY73q1EgDa2

G E N E R A L ^ ELECTRIC GCNCffAL CUCCTHlC COMPANY J U S tA|TQN T /*lNl(k0.e0NN 04JI 71 ti-.Cv./ .I EN P 006060 September 6, 1977 Irvins J'- Selikoff, M. D Professor of Community Medicine & Director - Environmental Sciences Laboratory He. Sinai School of Medicine Fifth Avenue & 100ch Street Mew York, N. Y. 10029 Dear Dr. Selikoff: This is to inform you that John F. Welch, Jr. ( -Vice President and Group Executive of our Components and Materials Group, has approved the research proposals included in your communication of August 3, 1977. He has agreed to provide funds not to exceed $94,389.00 to support the four research projects. He would, however, like you to consider the pertinent comments of John Brown tvho reviewed the proposal for Dr. Welch. In order to be brief and yet accurate, the significant quotes from John Brown's communication are as follows: Introduction: "In essence, I believe that we are getting very close to a mutually satisfactory study; that is, one chat will (a) define the health consequences (if any) of past exposure to capacitor-grace ?C3s, (b) elucidate the mechanisms of capacitor-grade PCS toxicity (if any) in the human, and (c) indicate the feasibility (chough not necessarily the desirability) of simple therapeutic measures to accelerate the removal of chronically-accumulated PC3s from the body. Particularly with a few minor technicalraodifications, I believe this could be a very worthwhile study, and'I would recommend your support." A. Mortality Study & B. Birth Defect Study "Regarding both of these statistical studies, I believe it very important that the data reflect as far as possible not only the fact of working in a plant where the exposure to PCB was possible, but also the identity of the particular PCB to which the employee was possibly exposed. The reason for my concern here is chat laboratory studies have repeatedly shown large differences .between the various 774709 GENP 006061 G E N E R A L ^ ELECTRIC Irving J. Selikoff, M. D. 2 September 6, 1977 PCBs in their biological effects, and hence I believe that it may be necessary to know whether the employee's exposure was to Arochlor 1254, 1242, or 1016 in order to make any sense out of the statistics. With a bit of help from the Capacitor Department people, such in formation on the probable identity of the FCB involved should not " be too hard to generate, once the dates and locations of employment are determined, since the overwhelming proportion of the exposure must have resulted from the practice of flood-filling, particularly of the large-volume small capacitor lines, and there does seem to be data available on whan they were using which PCB in which plant. (The story seams to be that Fort Edward shifted from Arochlor 1254 to 1242 on 9/22/50 and Hudson Falls shifted from 1254 to 1242 around 1955, back again for a year in 1957, and then permanently out of I254-except for minor special lines, around 1958'. Both plants switched from 1242 to 1016 around February, 1971, I believe.) At any event, I think this sort of information should be fished out and worked into the statistical analyses." C. Immunosuppression Study Cl. "This may be such an obvious point that Dr. Selikoff simply skipped over it in his proposal, but let me throw it in anyway. The proposed immunosuppression*study would involve subjects having had widely varying levels of exposure to PC3s in the past, and varying lengths of time since exposure ceased. In order to interpret the significance of any observed immunosuppression, it would be desirable to know what sorts of PC3 levels existed in the subject's blood in the past - which I presume can be determined from Dr. Wolff's earlier data - and, even more important, to know what levels were present at the time of the immunosuppression assay. Accordingly, an assay for blood PCB should be included as part of the test protocol. C2. As we have already mentioned to Dr. Selikoff, Drs. Kaplan and Uzgiris here at CHD have an ongoing program -to explore the feasi bility of detecting changes in the cell-mediated immune status of the body via laser-Doppler spectroscopy. -We.are not certain whether such studies of lymphocytes from PC3-exposed workers would be mean ingful; however, if Dr. Bekesi does run across any clear indications of abnormality, wa would like to be informed so that we could have a look at the mobility distribution patterns and antigen responses in the deviant cases." D. PCB Elimination Studies. Dl. "This particular study involves at least four separate experinenc: and the results could have bearing on several different unresolved cue: tions. One of the less obvious of these is what it is that actually 774710 GlERAl*2 electric Irving J. Selikoff, M. D. 3 September 6, 1977 happens in cases of overt "PCB" (e.g., probably PCDF)poisoning, as at Yusho. One remarkable, and as yet still unexplained observation made by the Japanese was that the Yusho victims showed a markedly abnormal distribution of residual PCB isomers in their blood. This could have resulted from an abnormal activation of microsomal enzymes. If so, it might appear in the 1254-fed rats subsequently dosed with phno barbital or B-naphthoflavone. Accordingly, I would recommend*that in these experiments there be notice cade of the PCB isomer distribution patterns as well as the rate of disappearance of cecal PCB. D2. I note that the proposed study will include testing of silica gel as one example of a ''powerful" adsorbent. Actually, silica is a powerful adsorbent for weakly polar organic compounds only from solutions in-weakly-polarsolvents, not from solutions in water. Unless the silica gel experiment is intended solely as a control, it might well be omitted. D3. .Any clinical use of agents to stimulate PCB elimination will require some documentation of the inability of natural processes to take care of the problem; i.e., longitudinal studies of PCB levels in Capacitor Department employees following cessation of exposure. .1 am somewhat disappointed to see that no specific provision for such studies is included in the proposed program. I note, however, that if the blood-PCB assays that I suggested under Section Cl be carried out, these, in conjunction with the earlier data on blood PCB levels, ought to provide the required data on at least 50 sub jects, and this should be enough to indicate the trends regarding PCB persistence in chronically-exposed humans." As we agreed by telephone, the funding arrangements will be completed by the individual(s) responsible for financial affairs at the Mt. Sinai School of Medicine and in Dr. Welch's organization-. Once you have made the appropriate communication at Mt. Sinai, this person should contact Dr. Welch's designate: James J. Costello Manager - Group Financial Planning & Analysis General Electric Company 1 Plastics Avenue Pittsfield, MA 01201 Tel.: (413) 494-5432 A.s you are aware, I am pleased with this combined approach to a naughty problem and hope we can get started in the near future. Sincerely, G E N P 00606 o r o v .T i, j ~t J. F. Welch, Jr bcc: R. L. Frigo H. D. Pocock, M. D. 774711