Document jwJ9Nk12kGzkdYEBMrYVD21N

Chemical Manufacturers Association Record of Meeting f'' - " ' VINYL CHLORIDE AUDIT TASK GROUP Experimental PathologyLaboratories, Inc. Herndon, Virginia . May 1-2, 1979 Dr. Z. G. Bell, Chairman, presided and opened the meeting 3:40 p.m. The following members and guests were present: MEMBERS PRESENT Z. G. Bell, Chairman T. J. Benya G. K. Hatfield R. K. Hinderer V. L. Kirkland a* T. R. Torkelson PPG Industries, Inc. Ethyl Corporation Diamond Shamrock Corporation The BFGoodrich Company, Chemical Division Shell Oil Company The Dow Chemical Company J. T. Seawell CMA Staff a. for C. D. Kary PRESENT BY INVITATION W. M. Busey Experimental Pathology Laboratories, Inc. 1.0 Assessment of Available Audit Data The phase of this meeting was concerned with the evaluation of the audit data acquired to date to include data from the on-site audit session of February 19-24, 1978, the tissue inventory completed by Industrial BIO-TEST Laboratories, Inc. (IBT), and the "VINYL CHLORIDE PATHOLOGY REPORT" prepared by Experimental Pathology Lab oratories (EPL). As a result of these data assessments, it was apparent that any possible additional histopathologic work would be contingent upon a complete accountability study based on the following three data categories: i^i (hi H DTH 000013181) 2- - a) Total number of tissues to be saved by IBT for histopathologic study as required by the protocol, b) Total number of tissues examined by IBT pathologists, and c) Total tissues saved by IBT personnel. 2.0 Initial Observations of the Vinyl Chloride Audit Task Group, (VC-ATG) Based on Data Evaluations____________________________ The following observations were made by the VC-ATG after its evaluation of the audit and inventory data available at the beginning of this audit session: a) Personnel responsible for the conduct of this study are no longer with the contractor's organization and we have been informed that the organization itself will cease to exist as of January 15, 1979. This precludes verbal reconstruction of certain critical test parameters, procedures, and records, b) Important records which have not been audited to date include: 1. Animal purchase orders 2. Shipping and receiving records 3. Analytical records of exposure chamber concentrations 4. Randomization of test animals 5. Animal weight and survival records 6. Records of health, behavior, and other observations 7. Logbooks It appeared to the ATG that there was little value in auditing the documents cited above unless there were adequate pathologic materials and records available which would enable arrival at sci entific valid conclusions as to tumor incidence and to dose response relationships. Therefore, as a first step, the ATG choose to con cern itself with a partial audit of existing tissues, slides, blocks and records of gross and histopathologic examinations. 3.0 Tissue Accountability Study As in the initial audit sessions, it was necessary for the ATG to divide into teams in order to cover all organs required by DTH 000013190 -3- the protocol for all three test animals and all test groups. Each audit section prepared an audit/tissue recapitulation based on the original tissues as stipulated in the protocol, the tissues actually examined by IBT pathologists, and total tissues saved in the form of wet tissues, tissue blocks, or slides. Evolving from the May 1-2 audit is the following accountability summary of total tissues saved: TOTAL TISSUES SAVED Test Animals Tests Groups UC Total % Tl Total % Males Rats 998 24.9 930 23.3 Mice 497 12.0 548 13.7 Hamsters 511 12.8 485 12.1 Females Rats 1263 32.4 853 21.9 Mice 402 10.0 599 15.0 Hamsters 372 9.5 406 10.0 T2 Total % 1061 26.5 739 16.0 743 18.5 908 23.3 942 24.0 677 17.4 T3 Total % 1106 27.7 766 19.0 761 19.0 970 24.9 910 23.3 454 11.4 T4 Total % ---- 856 21, -_ As may be observed in the foregoinq tabular studies, total tissues saved ranged from a low of 9.5% to a "high" 32.4% in any given test group. The high is 62.6% below the generally recognized minimum acceptable level. 4.0 Opinions of the VC-ATG Concerning Conduct of Study It is the opinion of the ATG that the technical conduct of this study has been grossly deficient as indicated by the following list of partial observations: DTH 0000131SH -4- 1) IBT failed to save most tissues as specified in the protocol, 2) IBT failed to conduct histopathologic examinations of many of the tissues that were saved. 3) Even though all currently available (according to the IBT conducted inventory) tissues were to be examined, the number would be grossly inadequate to complete the objective of the study. 4) Failure to examine sufficient organs from sacrificed animals. As an example of observation 4) presented above, of 42 male rats in the top dose level (exposure concentration of 2,500 ppm) surviving at the end of one year exposure period, only brains from nine animals were saved for histopathologic examination. Of these, only four were worked up into microscopic slides and examined. Hence, 90 per cent of the brains of those animals surviving to the most critical period were never examined. The Task Group concluded its auditing sessions with the following recommendation which carried unanimously: We recommend that CMA proceed with the necessary steps to have IBT rerun the entire study or refund all funds paid to IBT by CMA under the research agreement on vinyl chloride. The ATG AGREED: That in arriving at the recorded recommen dation the ATG had in large measure been guided by the report entitled "VINYL CHLORIDE PATHOLOGY REPORT", dated January 9, 1979, prepared by William M. Busey, D.V.M., Ph.D. of Experimental Pathology Laboratories, Inc. The ATG further AGREED: That it concurs with Dr. Busey's recommen dations as presented on pages 5 through 8 of the above-mentioned report. DTH 000013192 I -5- The Task Group recommended that the Project Administrator write the complete final report of the Vinyl Chloride Audit Task Group. Among other important documentations, the following components are to form integral parts of the final report: 1) An appropriate summary of the study protocol. 2) Typed copies of all audit work sheets evolving from the studies of the four audit teams conducted on May 1-2, 1979. 3) A total tissue accountability summary to include: a. Tissues required by the protocol b. Tissues examined by IBT pathologist(s) c. Total tissues available according to the IBT inventory completed at the request of the VC-ATG. 4) The report entitled "VINYL CHLORIDE PATHOLOGY REPORT", dated January 9, 1979, prepared by William M. Busey, D.V.M., Ph.D,, of Experimental Pathology Laboratories, Inc. JTS:pmt Record Subject to Approval May 23, 1979 T. Seawell Project Administrator Vinyl Chloride Research DTH 0000131553