Document g2zZNwmdENZMQkL95j1QvbrzV

From: Sent: To: Subject: Attach: Cagen, Stuart Z SCC-CF-SS <stuart.cagen@shell.com> Friday, November 12, 2004 7:48 PM (GMT) 'shan tsai' <shantsai@hotmai1.com>; Clegg, Patsy M SCC-CHSE-PC <patsy.c1egg@shell.com>; Tsai, Shan P SHLOIL-SHS <Shan.Tsai@shell.com> RE: draft presentation for your review Shanghai Health Study review and update 16 November 2004.ZIP New version for your review. Slightly reduced and I have incorporated most of Shan's suggestions. Note I have kept 20 ppm as the 'threshold' value, not 5 ppm as Shan has suggested but I have changed the language from risk to association ... Comments? Perhaps we should talk sometime on Monday. Stuart Stuart Cagen Shell Chemical LP One Shell Plaza, 910 Louisiana, Houston, TX 77002-4916 Tel: +1 713 241 1407 Fax: +1 713 241 3325 Other Tel: +1 832 646 3987 Email: stuart.cagen@sheILcom Internet: http://www.sheILcom/chemicals -----Orig inal Message----From: shan tsai [mailto:shantsai@hotmaiLcom] Sent: Thursday, November 11, 2004 12:09 AM To: Cagen, Stuart Z SCC-CF-SS; Clegg, Patsy M SCC-CHSE-PC; Tsai, Shan P SHLOIL-SHS Subject: RE: draft presentation for your review Stuart, The presentation materials look very good. I have only a few suggestions: 1. Epidemiology Conclusions Pre-1997: the clear risk at exposures is too high. May need to lower to >5ppm. Also change issufficient data to 1-5 ppm 2. Austrilian study - Add "at lower level of benzene exposure" after the first bullet of that slide 3. In the How is the SHS Distinct - what you mean by "the first-hand exposure reports" 4. In the Study #1 - Case Control Study, first bullet, delete "potentially" 5. Overall, too much detailed information in this presentation. Shan Taiwan >From: "Cagen, Stuart Z SCC-CF-SS" <stuart.cagen@sheILcom> >To: "Clegg, Patsy M SCC-CHSE-PC" <patsy.clegg@sheILcom>,"Tsai, Shan P >SHLOIL-SHS" <Shan.Tsai@shell.com>,<shantsai@hotmail.com> >Subject: draft presentation for your review >Date: Tue, 9 Nov 2004 14: 15:02 -0600 > > > Shanghai Health Study update 16 November 2004.ZIP > > >Stuart Cagen SH ELL-MCCLU RG-054489 > >Shell Chemical LP >One Shell Plaza, 910 Louisiana, Houston, TX 77002-4916 > >Tel: +1 713 241 1407 Fax: +1 713 241 3325 Other Tel: +1 832 646 3987 >Email: stuart.cagen@shell.com >Internet: http://www.shell.com/chemicals > > ShanghaiHealthStudyupdate16November2004.ZIP SH ELL-MCCLU RG-054490 Shanghai Health Study: review and update 16 November 2004 SHELL-MCCLURG-054491 Shanghai Health Study Benzene toxicology and regulations Shanghai Health Study (SHS) providing an opportunity to clarify scientific issues Status Shell participation Current challenges SH ELL-MCCLU RG-OS4492 Benzene toxicology and regulations Two important steps in the management of toxic chemicals: 1) Hazard Identification - what are the hazards, regardless of exposure. 2) Risk characterization - dose response - what is a safe dose. SH ELL-MCCLU RG-OS4493 II I think ynu should be n10re ""p'll' -l"e n' i.::1te fatt- t''e~.2l~. . Cl". .i> .. L lIt: .' ..... l' . a 1-r-ffi . "tTtl)' '. II SH ELL-MCCLU RG-OS4494 Understanding Benzene Toxicity SH ELL-MCCLU RG-054495 Benzene toxicology and regulatory issues Two important steps in the management of toxic chemicals: 1) Hazard Identification - what are the hazards, regardless of exposure. 2) Risk characterization - dose response - what is a safe dose. SH ELL-MCCLU RG-OS4496 Benzene Is ... Hazard Identification - what are the hazards, regardless of exposure: - A recognized - known - human carcinogen: Acute Myelogenous Leukemia (AML) SH ELL-MCCLU RG-OS4497 Benzene Toxicity The effects of exposure to any hazardous substance depend on: - dose, - duration, - other exposures, - personal traits and habits, - genetic susceptibility SH ELL-MCCLU RG-OS4498 Epidemiology Conclusions pre-1997 Acute Myelogenous Leukemia (AML) associated with benzene - Not seen at exposures < 1ppm - Clear observations at exposures> 20 ppm - Insufficient data at 1-20 ppm to clearly assess risk Some steps are not dose-dependent and are governed by a threshold mechanism All steps required for induction of cancer have not been determined SH ELL-MCCLU RG-OS4499 Benzene Is ... Tightly regulated although worldwide standards vary: - Work place exposure levels in the range of 0.5 - 10 ppm - Regulations in the US via the Clean Air Act might limit community levels to as low as 40 ppt. SH ELL-MCCLU RG-OS4S00 Recent Epidemiological Studies National Cancer Institute Shanghai Study (NCI) - case-control study published in 1997 - Benzene associated with AML and Non Hodgkin's Lymphoma (NHL): unusual association with a non-AML cancer - Study design did not add to understanding of threshold (lowest exposure group was 10 ppm or less) SHELL-MCCLURG-054501 Recent Epidemiological Studies Australian Institute of Petroleum's (AlP) Health Watch Study - case-control study released in 2001 - Association with all leukemias, including chronic lymphocytic leukemia - Leukemia association reported at lower levels than prior studies. - No association with NHL or multiple myeloma SH ELL-MCCLU RG-054502 Benzene Is ... Hazard Identification - what are the hazards, regardless of exposure: - A recognized - known - human carcinogen: Acute Myelogenous Leukemia (AML) Other Lymphoid or Hematopoietic Diseases have been suggested. SH ELL-MCCLU RG-054503 Ai:.ulp. Nly,pbl! M:-uto emlill i/IML, ~I:o\.. trifU IaUI iIII11lt: Ii:l)i;l!'mill ~AUI l.Ic~ ly.mphabl..d'lt) ~~II Chr(lf1;r;: 8l}r"Ip'"I~""'t: ieltkKlla fE-CUj leukemias 13-[l!!1 :!ImIII1 ~I!': ii/mphOl1lIl Lymphomas ~'I",~~m hltJlItlilli1Ifo, ,AM:.:! i'J"'.,JI1l- t;!. ~ilS~"!i 1>!o~l!:f"I,a {AlL~: aeeM ~I~ ~l\tIo'M (,;tlrl;.m~ ~-./y",phr.yt.c 1~1;/~1:"'i8 ~b.Cll; O--D&1i :srMf. 'J'ii~r~" t'l''''I~ 6 of 11 SH ELL-MCCLU RG-054504 Current Science No definitive epidemiological evidence to define a threshold NCI and AlP studies conflict with earlier studies by associating benzene exposure with non-AML cancers Disease classification clarified SHS designed to qualitatively and quantitatively address these issues SH ELL-MCCLU RG-054505 Shanghai Health Study Purpose To gain a quantifiable understanding of the relationship between benzene exposure and potential associated cancer risks - Researchers using cutting-edge technologies to advance the understanding of benzene-induced disease SH ELL-MCCLU RG-054506 Health Effect Study of Benzene in Shanghai AML/NHL Case Control Study I AAlM DS/AML/B P Disease Progress Study Molecular Epidemiological Study of Benzene Exposure I Joint Sino-US Clinical and Molecular Laboratory ( JCML) SH ELL-MCCLU RG-054507 Sino-US. Joint Clinical and Molecular Laboratory SH ELL-MCCLU RG-054508 Referral Hospitals Outside Benzene Cases Factories Clinical Laboratory Support L I JCML Laboratory Consultation Exposure SMCDPC SMIPHS Case Control Disease Progression Molecular Epidemiolog~ SH ELL-MCCLU RG-054509 SHS Elements Case Control Study Disease Progression Study Molecular Epidemiology Quality Science Scientific Review Panels Current Status Scientific and Ethical Reviews Projected Timeline SHELL-MCCLURG-054510 Specific Study Goals Understand relationship, if any, between benzene exposure and development of specific hematopoietic diseases: AA, MDS, AML and NHL - Causation of specific diseases/subtypes - Mechanism of disease progression - Dose-response relationships - Identification of cofactors and confounders - Identification of biomarkers of exposure and disease progressI on SHELL-MCCLURG-054511 Study #1 - Case Control Study Prospective epidemiology study to determine risk of AML and NHL, among benzene exposed workers Data collected will allow analysis of potential other causal factors for NHL Estimate 4 to 5 years to obtain 450 AML and 450 NHL patients into study Improved exposure assessment based on historical and concurrent workplace monitoring and questionnaire SHELL-MCCLURG-054512 Study #2 - Disease Progression Prospective study on relationship of non-cancer bone marrow disease and benzene-induced AML - Is benzene-induced AML different from spontaneous AML by unique cellular markers? - Does AML involve a progression through one or more noncancer states? Research methods: questionnaires, interviews, review work histories; examine blood, breath, urine study/evaluate potential biomarkers SHELL-MCCLURG-054513 Study #3 - Molecular Epidemiology Prospective study of establish quantitative relationship between exposure and effect - Do low benzene exposures cause blood effects? - Is there an association of blood effects and genetic susceptibility? - Do biomarkers of exposure accurately reflect workplace exposures? Healthy workers at sites with varying levels of benzene exposure will participate; extensive lab work, including genetic tests, will be conducted SHELL-MCCLURG-054514 Quality Science Protocols approved by external Institutional Review Boards (IRB' s) - Govern use of human subjects - u.s. and China independently Shanghai Health Study panels - International Ethics Expert Panel - International Scientific Expert Panel 10 members 6 scientific disciplines - Involved during entire project SHELL-MCCLURG-054515 Shanghai Health Study Study Participants Principal Investigators: Dr. Richard Irons, U of Colorado Health Sciences Center Dr. Otto Wong, Applied Health Sciences Dr. Fu Hua, Fudan University Collaborators: ExxonMobil Biomedical Sciences Chinese Participants: Fudan University School of Medicine 30 area Shanghai hospitals Shanghai Municipal Center for Disease Prevention Shanghai Hematology Society Shanghai Pathology Institute for Public Health Supervision Shanghai Public Health Bureau Internal Review Boards U of Colorado, Fudan University SHELL-MCCLURG-054516 SHS Projected Timeline Questionnaire development, pilot testing in progress, 2002 Key laboratory personnel trained, 2002 Laboratory complete, 2003 Laboratory opening, summer 2003 Case recruitment began - 4th quarter, 2003 - 1600 benzene exposed workers, 400 controls - Time necessary to identify qualified patients - Length of study may be extended if required Research, analysis expected 2003-2007 Results published as studies completed SHELL-MCCLURG-054517 Sino-U.S. Joint Clinical and Molecular Laboratory (JCML) State-of-the-art laboratory constructed on Fudan University campus - Built according to international standards - Lab will support the project, Shanghai medical community and remain at Fudan Technology transfers - Chinese staff receiving training at University of Colorado - U.S. researchers working with Chinese colleagues and government officials on methodologies, questionnaires, processes, etc. SHELL-MCCLURG-054518 Who is Sponsoring the SHS? A consortium of petroleum and chemical companies concerned about understanding the human health effects of benzene - BP, ChevronTexaco, ConocoPhillips, ExxonMobil, Shell Chemical with additional funding from Marathon Ashland - Project Administrator: American Petroleum Institute SHELL-MCCLURG-054519 Sponsor infrastructure: Shanghai Health Study Consortium Organization Oversight Committee Technlc/a I Commutn.lca.tlon Rectru.ltment LegaI t1 Scientific Review Panel APCO Ethics Review Panel API Administrative Support SH ELL-MCCLU RG-054520 Shell participation Shell currently holding consortium leadership positions: Patsy Clegg - consortium oversight committee Chair Stuart Cagen - technical committee Vice-Chair and Chair of finance committee Shan Tsai - adjunct professor, Fudan University Sarah Colletti/Lauren Iannarone, communications committee SHELL-MCCLURG-054521 Shanghai Health Study Shell intentions for project and outreach Shell intentions to be based on: - Product stewardship needs for hazard and risk clarity. - Protecting reputation - in China and around the world. - Protect relationships/investments in China. - Meet commitment to transparency and ethics. - Protect credibility of project and participants. - Raise awareness and understanding of the project. - Secure buy-in and constructive feedback into the process. SH ELL-MCCLU RG-OS4S22 Current challenges Budget Exposure assessment Sustainability of the lab (JCML) SH ELL-MCCLU RG-054523 Shanghai Health Study Budget (approved November 2003): $ 21.08 M (Shell portion: $ 4.2 M) Supplemental funding request (November 2004): $ 3.3M (Shell portion not yet estimated) Not currently approved by consortium Due in part to initial study delays (eg., SARS in China) Due in part to unexpected difficulties in program management via Shanghai partners, including limited access to locations with higher benzene exposures. SH ELL-MCCLU RG-OS4S24 Shanghai Health Study Exposure assessment difficulties related to the level of active participation of Shanghai partners and more difficult than expected historical occupational data base. Exposure assessment issues possibly optimized but not solved with supplemental funding. SH ELL-MCCLU RG-054525 Shanghai Health Study Laboratory (JCML) sustainability beyond the study is currently a SHS sponsor consortium issue: Sponsor consortium favors efforts to maintain the laboratory. Laboratory brings a unique and important resource to the Shanghai medical community. Financial sustainability of the laboratory is primarily the responsibility of the current owner (Fudan University). SH ELL-MCCLU RG-054526