Document 5pOzVo83rNqmEny9peZ4G45z

PROJECT STATUS: MANUSCRIPT #1 Re-Evaluation of Benzene Exposure -i-n Pliofilm Manufacture "- ..~l .. - "Final" draft completed October 23, 1990 Received comments on draft from Drs. Crump and Goldstein Hanning, Allman, Osborne interviews 02-08-91 &E-1 BP-00010257 IMPLICATIONS OF THE HANNING INTERVIEW Solvent recovery always used in Pliofilm manufacturing made process economically feasible 93% effective During WWII Pliofilm casting units at St. Marys converted to production of tent {abric No benzene used unless scrap Pliofilm available 02-08-91 BP-00010258 .. IMPLICATIONS OF THE HANNING INTERVIEW (cont'd) Masks provided to workers and required in areas where benzene was used Filters on masks changed regularly Workers often failed to use masks - Casting operations were separate from other Pliofilm operations. Therefore, general emissions from casting operations can not be used to estimate exposures to other workers Dermal contact was_appreciable 02-{)8-91 &1>3 BP-00010259 IMPLICATIONS OF THE HANNING INTERVIEW <cont'd) -~ St. Marys monitored blood monthly while Akron monitored blood quarterly Air monitoring was done to prevent explosions, not for health reasons Much of Wilson testimony may have applied to other processes at Goodyear Kigen data appears consistent with the lack of Pliofilm manufacture aL St. Marys (1942-1945) 02-QS-91 &1>4 BP-00010260 IMPLICATIONS OF THE OSBORNE/ALLMAN INTERVIEWS Mixer, reactor, and neutralizer tanks vented to scrubber Not on Risky diagram Open trough used to transport rubber hydrochloride from reactor to neutralizer Exact years unknown Workers supplied with rubber gloves (which may not have been effective) General room dimensions (assists with mass balance calculations) 02-08-91 &1>5 BP-00010261 PHASE IT Re-Evaluation of Benzene Exposure in Pliofilm Manufacture 02-08-91 New approach: time-and-motion study to quantify uptake during peak exposure periods Baseline exposures calculated; peak exposures in progress Differences between us and Crump & Allen: 1.5 x C&A; all else the same Conduct sensitivity analysis of linear and other models Funaing: $113,000 spent to date Expected timetable: Draft revised document by-March 30; Perhaps, revision needed by time of ACGIH meeting BP-00010262 PROJECT STATUS: MANUSCRIPT #2 Benzene-Induced Leukemia: An Examination of Disease Endpoints First draft of manuscript submitted October 24, 1990 Some comments received; paper considered "not compelling" Detailed outline written-for second draft 02-08-91 ~1 BP-00010263 .. PROJECT STATUS (cont'd) Benzene-Induced Leukemia: An Examination of Disease Endpoints Our case may not be sufficiently strong to be useful;_ however, choosing AML or AML + CML may not make much difference Awaiting further- review and direction from Task Force Funding: $54,000 spent to date Timetable: Second draft will be completed 2 weeks after conference cail; draft by March 1st is likely 02-QS-91 BP-00010264 PROJECT STATUS: MANUSCRIPT #3 Re-Analysis of the Pliofilm Cohort Using Linear and Linear-Quadratic Models Contract in-place with Clement International Awaiting development of revised Pliofilm exposure estimates Budget: $78,000. No expenditures to date. 02-{)8-91 BP-00010265 SUMMARY OF DELIVERABLES/ACCOMPLISHMENTS February 12, 1991 Completed much of learning curve by October 1st Updated toxicology, industrial hygiene, and exposure information on 1940s-1960s benzene levels Re-examined Akron Library, Silverman Library, Industrial Health Foundation Library Met with Goodyear executives Met with Pliofilm employees Completed dr:aft of publishable exposure manuscript by October 23rd Completed draft of unpublishable "endpoints" paper by October 24th 02..()8-91 BP-00010266 NECESSARY 1Ml\1EDIATE WORK Re-interview Hanning Interview Pliofilm nurse I~terview Sakol (Akron physician) contacts Draw-up Pliofilm building plans (plan and overhead view) Look at old drawings of process Cenduct sensitivity -ana-lysis of the "responsiveness" of the three models to changes in exposure data 02~8-91 &loll BP-00010267 POSSffiLE LONG-TERM PROJECTS MVK model Upgrade PB-PK model Evaluate update of Rinsky cohort Conduct meta-analysis of Pliofilm, Ott, Wong, etc . 02-08-91 BP-00010268 POSSffiLE 1991 TASKS FOR ChemRisk INVOLVING BENZENE February 12, 1991 Dennis J. Paustenbach, Ph.D. Jim Jernigan, Ph.D. Presented to the API/WSPA Benzene Task Force 02-08-91 BP-00010269 POSSIBLE 1991 BENZENE PROJECTS Task 1.0 An Evaluation of Epidemiological Studies Used to Assess the Risk of Benzene-Induced Leukemia Task 2.0 Justification for Using the Linear-Quadratic Model for DoseResponse Extrapolation of Benzene Risk Task 3.0 Evaluation of the Congruence of the Human Epidemiological Data with the CDHS Animal-Based Upper Bound Unit Risk for Inhaled Benzene Task 4~0 Assessment of Leukemia Risk Using the MVK Model Task 5.0 Evaluation of the Congruence of the Human Epidemiological Data with the_ CDHS Animal-Based Lower Bound Unit Risk for Inhaled Benzene Task 6.0 Comparison of Extrapolation Models for Benzene--Induced Leukemia 02-{)8-91 BP-00010270 Task 1.0 An Evalllation of Epidemiological Studies Used to Assess the Risk of Benzene-Induced Leukemia Objective: Demonstrate that the Pliofilm cohort provides the most scientifically valid and precise exposure-response data for use in extrapolation modeling. Review and re-package Clement (1988, 1989) arguments Review and outline Brett~ ill. (1989) arguments Review Ott J;J; ill.. (1978), Wong (1983, 1987) Write manuscript for journal Revise manuscript as suggested by journal Estimated cost: $ 39,609 Schedule; Start; First draft: Revised draft: Submission to journal: March 1, 1991 6 weeks after authorization 4 weeks after first draft As early as June 15, 1991 02-08-91 BP-00010271 Task 2.0 Justification for Using the Linear-Quadratic Model for Dose-Response Extrapolation of Benzene Risk Objective: Present evidence that a linear-quadratic model is the most valid approach for assessing the leukemia risks for the Plioftlm cohort. Review and re-package Clement (1988, 1989) arguments Review and outline Georgetown document Review and outline applicable sections of BIER V -(1990) Use PB-PK data developed by Travis to pick the "break-point" on dose-response curve where it will change from quadratic to-linear Write manuscript; present and justify each of the Clement/Georgetown recommendations Revise manuscript as suggested by journal Estimated Cost: $ 48,365 Schedule: Start: First Draft: Revised Draft: Submission to journal: 02-08-91 April 5, 1991 6 weeks after authorization -10-days after receipt of comments July I, 1991 (earliest possible submission) BP-00010272 Task 3.0 Evaluation of the Congruence of the Human Epidemiological Data with the CDHS Animal-Based Upper Bound Unit Risk for Inhaled Benzene Objective: Evaluate whether the CDHS approach is unrealistic. Determine whether the number of cancer deaths predicted by the CDHS approach is substantially higher or lower than the numbe!:..observed in Pliofllm workers. Review and outline Clement (1990) arguments Write manuscript Revise manuscript in response to comments Estimated cost: $ 39,041 Schedule: Start: First draft: Revised -draft: Submission to journal: March 15, 1991 6 weeks after authorization 10 days after receipt of comments July 14, 1991 (earliest possible submission) 02~891 BP-00010273 Task -4-.() Assessment of Leukemia Risk Using the MVK Model Objective: Make a "first-cut" att..empt in developing a cancer potency estimate using default assumptions in the MVK model and conduct a sensitivity analysis to "bracket" the data Assign values to the parameters-bh b2, b3, b4; provide justification for the values chosen -e- Subcontract with Dr. Max Layard or Dr. Rory Connollt to evaluate the model Write the manuscript Revise the manuscript in response-to comments Estimated Cost: $ 52,244 Schedule: Start: First draft: Revised draft: Submission to journal: August 1, 1991 6 weeks after authorization 4 weeks after first draft Nov. 24, 1991 (earliest possible submission) 02..()8-91 BP-00010274 ' Task 5.0 Evaluation of the Congruence-of the Human Epidemiological Data with the CDHS Animal-Based Lower Bound Unit Risk for Inhaled Benzene Objective: Evaluate whether the CDHS approach is unrealistic. Determine whether the number of cancer deaths predicted by the CDHS approach-is substantially higher or lower than the number observed in Pliofilm workers. Review and outline Clement arguments Write manuscript Revise manuscript in response to comments Estimated cost: $ 40,080 Schedule: Start: First draft: Revised draft: Submission to journal: August 16, 1991 5 weeks after authorization 10 days after receipt of comments November 20, 1991 (earliest possible submission) 02.{}8-91 ------------------------------------------- BP-00010275 ', Task 6.0 A Comparison of Extrapolation Models for Benzene-Induced .Leukemia Objective: Review the evidence for using each of the following models for various leukemogenic risks posed by benzene exposure: conditional logistic regression, linear, MVK, quadratic, linear-quadratic Understand each model Evaluate fit in observable range Evaluate "responsiveness" to small changes in the data Evaluate biologic underpinnings of each model Estimated cost: $ 43,445 -schedule: Start: First Draft: Revised Draft: Submission to journal: 02-08-91 November 15, 1991 6 weeks afte.- authorization 14 days after receipt of comments February 20, 1992 (earliest possible submission) BP-00010276