Document 06EV28NK4Yqna37EJyyXGeJOm

Shanghai Health Study Update to API HESGC Patsy Clegg Chair, Oversight Committee November 20, 2008 SH ELL-MCCLU RG-065388 Shanghai Health Study Update The purpose of the Shanghai Health Study is to gain a more refined understanding of the relationship between benzene exposure and potentially associated human health effects. SH ELL-MCCLU RG-065389 Shanghai Health Study Update 3 Stu d es.'~;~;t:fl~it~t~:~;:::;;: -I :I;:~:~: AML and NHL prospective case study ::I}I: Disease Progression study ~I;I~ Molecular Epidemiology study :~:~:I;:~:~ Studies done at Fudan University in Shanghai I}I: Laboratory donated to Fudan !Ii;I! Chinese scientists participated in study SH ELL-MCCLU RG-065390 Shanghai Health Study Update Study Case Accrual Complete.'~;~;t:fl~it~t~:~;:::;;: :I;:~:~: >500 AML cases (acute myelogenous leukemia) ::I}I: >500 NHL cases (non-Hodgkins lymphoma) ~I;I~ Protocols set a goal of 500 cases for each !:~:;I:~:~: Publications have appeared in scientific literature :~:~:i;:::! Anticipate publications on all 3 studies in 2009 SHELL-MCCLURG-065391 Shanghai Health Study Update Invest-Igators.t:l:~~fr1)~ti~~:l:r. ~:~}::~: Richard Irons, Principal Investigator, Cinpathogen I:,':~: Otto Wong, Applied Health Sciences ~:~:}::~: Fu Hua, Fudan University I:::~:~: You-Xin Liang, Fudan University I::I~: Rob Schnatter, EMBSI SH ELL-MCCLU RG-065392 Shanghai Health Study Update i:~::i:~:i Scientific and Ethics Review Panels ::':: Provide expertise and review to investigators :~:~I:~:~: Quality Assurance company hired to do QA/QC ::~:!:~:: API oversight provided by General Committee on Special Programs SH ELL-MCCLU RG-065393 Shanghai Health Study Update :~::~:i::~::~: Hi9hIi9hts ::":: WHO classification of tumors applied :}:: Nutritional anemias identified :}:: Benzene Induced Dysplasia - indicates benzene may have a unique signature TSCA 8Ce) filed I::,:::::: Lab transferred to Fudan University School of Medicine ::':: Cinpathogen, a private company, replaced University of Colorado as lead institution SH ELL-MCCLU RG-065394 Shanghai Health Study Update Path Forward Case accrual completed Data analysis Publications International Benzene Symposium in Munich Benzene Health Research Consortium will disband SH ELL-MCCLU RG-065395 Benzene Health Research Consortium Sponsoring Companies ~ BP ~ Chevron ~ ConocoPhillips ~ ExxonMobil ~ Shell Chemical LP Marathon/Ashland providing additional support SH ELL-MCCLU RG-065396 Shanghai Health Study .:. Budget .:. Funding Costs $ 35M $ 35M SH ELL-MCCLU RG-065397 Shanghai Health Study Summary :~::i::~: Case accruals met protocol goals :~:::i::~: Budget adequate to complete study :~::i::~: Lab at Fudan may continue to provide services to Shanghai community :~::i::~: Publications expected in 2009 :~:::i::~: Study will be reported at International Benzene Symposium in Munich in 2009 :~:::i::~: Sponsors consortium will disband at the end of 2009 SH ELL-MCCLU RG-065398 Shanghai Health Study API HESGC Update November 20 2008 Presented by Patsy Clegg, Chair Oversight Committee Benzene Health Research Consortium SH ELL-MCCLU RG-065399 The Shanghai Health Study Benzene Health Research Consortium 1 SH ELL-MCCLU RG-06S400 Presentation Topics ~:::itl:~::t::::~:mm:~:::: Shangha-I Health Study Overv-Iew :~fJ~t.':t~~{:~i~~r Current Benzene SC-Ience ~:~::.:~:~ Shanghai Health Study Elements ::;::: Shanghai Health Study Sponsors ::;::: Shanghai Health Study Funding Structure ~:::itl:~::t::::~:~~~~~~:f: TermsI Sources and Resources 2 SHELL-MCCLURG-065401 What is the Shanghai Health Study? ::~:I:~: A long-term clinical study to investigate the potential causes and development of Iymphohematopoietic diseases (diseases of the lymphoid organs, blood and bone marrow) as related to benzene ::~:!:~::~ A project of Fudan University Medical Center; University of Colorado Health Sciences Center; Applied Health Sciences - an independent U.S. research firm; Chinese public health agencies; and Shanghai hospitals 3 SH ELL-MCCLU RG-065402 Shanghai Health Study Purpose Ct To gain a quantifiable understanding of the relationship between benzene exposure and potential associated cancer risks ~:~:H:~:~ Researchers will use cutting-edge technologies to advance the understanding of benzene-induced disease 4 SH ELL-MCCLU RG-065403 Benzene Is ... i::::::::::::::::: A constituent of crude oil and a chemical building block ::::;:;:;ff}fitf: A recogn-Ized human carc-Inogen :i::::=:iIi Acute Myelogenous Leukemia (AML) :::::::::1::::::: Tightly regulated although worldwide standards vary :;::itif(;)ft;i:;:;. What -IS not currently known :1,HI: benzene's impact on a molecular level; :(I{::: the "threshold" exposure level; :(HI:: whether and how associated cancers or other related disease~ may be caused; and :i:HI the role of genetic susceptibility 5 SH ELL-MCCLU RG-065404 Benzene Toxicity C') The effects of exposure to any hazardous substance depend on: ~:~:H:~:~ dose, durati n,0i:i::i,:i::i:i :i:}-!:i:i: other exposures, :ti:t:i: personal traits and habits, ~i:i:!i~ genetic susceptibility C') Co-exposure to other chemicals can also influence toxicity 6 SH ELL-MCCLU RG-065405 Why is Understanding Benzene Important? ~t:~t:~:::;::::~:mm:~:::: Benzene exposure -IS un-Iversal C~ Advancing current scientific understanding of benzene exposure would be a significant contribution to health and worker safety c") Understanding heaIth effects of lowlevel benzene exposures would advance benzene science 7 SH ELL-MCCLU RG-065406 Why Shanghai? C') Unique Study Environment I:;"I: Databases documenting exposure :Ii'I: Exposure across industries I}I: Range of exposure levels Committed Collaborators =;::1111:1:::111::;; :I;:I: Government :::::!':I: University and hospital based researchers I:;"I: Community hospitals :Ii'I: Shanghai Municipal Center for Disease Control and Prevention iii::;,::::: Institute for Public Health Supervision 8 SH ELL-MCCLU RG-065407 Unparalleled Collaboration "Th-IS::::~:l:::~::::t~r::: study -IS an enormous collaborative effort, unlike anything America nand Chinese resea rchers have ever done. II - Dr. Richard Irons, PhD, SHS principal investigator, professor and director of the University of Colorado's Molecular Toxicology and Environmental Health Sciences Program 9 SH ELL-MCCLU RG-065408 Shanghai Health Study Background i:~::i:~:~: Most environmental and occupational standards for benzene are based on mathematical extrapolations of cancer risk from high-level exposures to environmental concentrations ::~:I:~:: These extrapolations are based on almost no knowledge of how benzene functions at a molecular level in humans 10 SH ELL-MCCLU RG-065409 Slides: Histology/Biology Ct Optional insert: slide examples of histological tissues and biological tissues 11 SH ELL-MCCLU RG-06S41 0 Difficulties in Past Benzene Research c") Animal models do not replicate human benzene-related diseases RetrosQect-lve resea rch:rit1~:t:.::::;;~;;;~;::::. -----+---:~:,::~ Review case files of people who have died ::~::: Rely on inexact diagnoses ~:::~: Accuracy of reconstructed exposure data :t:':!I: Guess at lifestyle and dietary habits 12 SHELL-MCCLURG-06S411 How is the SHS Distinct? ProsQect-lve resea rch::::~:}:1t~.::::;;~;;;;;::::. -----+---:~:i:~: Patients at participating hospitals suspected of having a lymphoid, blood or bone marrow disease will be referred to the SHS :~:i:~: Patients' diets, environmental exposures and family histories will be recorded :iI:i::::i:i: Patient disease progression followed at supporting hospitals 13 SH ELL-MCCLU RG-06S412 Shanghai Health Study Clinical Laboratory Support Sino-U.S. Joint Clinical & Molecular Lab Referral Hospitals Outside Benzene Cases Consultation SUJCML Laboratory Study Data Ex osure SMCDCP r+-_......iiiiiiiiiiiioiiiiliiio.........iiiioIiooiiiio_....j IPHS Case 1.0. Institute for Public Health Supervision Shanghai Municipal Centers for Disease Control & Prevention Case Disease Molecular Control Progression Epidemiology 14 SH ELL-MCCLU RG-06S413 How is the SHS Distinct? C. Study will be able to examine primary diagnostic and medical data in real time C. First-hand exposure reports are more reliable than second-hand or reconstructed information :~:iI:!:I:i; State-owned databases document worker histories 15 SH ELL-MCCLU RG-06S414 Shanghai Health Study Purpose Ct Designed to provide mechanistic data on AML development in humans Ct Goal to identify a more reliable basis for the extrapolation of leukemia risk associated with low-level benzene exposure 16 SH ELL-MCCLU RG-06S41S Shanghai Solutions i:::i::~: Unique Study Environment i:::i::~: Unparalleled Collaboration i:::I::~: Shanghai Health Study Genesis ~::::I:::: Ra re 0 pportu nity i::::::::::::::::: Shanghai Health Study Partners :~::i:::i Shanghai Health Study Hospital Partners :~::i:::i Sino-U.S. Joint Clinical & Molecular Lab 17 SH ELL-MCCLU RG-06S416 Unique Study Environment: Shanghai :~::I:~: Robust data set ::;::: State-maintained benzene exposure and health effects databases documented from 1970s i:[::::i:i Benzene related health effects are #2 in reported chronic occupational health hazards in China in 2001 (Source: Ministry ofPublic Health) I}I~ Large range of exposure levels from a variety of occupational sources :::;:: Regulatory authorities interest in improving benzene exposure regulation and enforcement 18 SH ELL-MCCLU RG-06S417 Unique Study Environment: Shanghai !:~:I:I:~!: China interested in scientific basis for improved worker-safety regulations !!!::{!!! Chinese occupational standards based on measurable human health effects :~:~:i:~:~ Chinese Occupational Diseases Protection Law (effective May 1/ 2002) ::{: Increases worker protections !:!::{:!: Specifies company role regarding worker health problems resulting from occupational exposures ::{: Benzene receiving additional scrutiny 19 SH ELL-MCCLU RG-06S418 Unique Study Environment: Shanghai c" High interest in collaborating on research ~!:.::~~ Technology transfers :~;I:{~:~: International health standards :::::::\::::::I::': State-of-the-art lab/ equlpment ~:;:::~i Sha nghai hematology/pathology communities support and expertise ~!:::~~ Strong research program supports China's regulatory understanding and objectives 20 SH ELL-MCCLU RG-06S419 Unique Study Environment: Shanghai f) Fudan University Medical Center iI!::ti:l Research partnership with a leading research university f' Community participation ~::':!~:l 16 hospitals will refer patients to the SHS i:i::::':::i:l Shanghai Municipal Center for Disease Prevention and Control :~:}:;:~:l Shanghai Institute for Public Health and Supervision 21 SH ELL-MCCLU RG-06S420 Unparalleled Collaboration Insert quote from Fu Hua or Fudan:::::::::~;:~:;1lm:;:;}::~::::t University OfficiaI 22 SHELL-MCCLURG-06S421 SHS Genesis i:~:!:~:i: NCIjCAPM study in Shanghai i:::::i:::::: Retrospective study published 1997 ::::::i:::::: Raised new questions on effects of low-level benzene exposure :i~::I:~:i Assessed feasibility of building on Shanghai experience :IiI Respected scientific collaborators I}I! Well-documented occupational exposure levels across variety of industries ::riI Detailed health and historical records i::::::'::::i Sufficient incidences of disease I:::'Ii Conclusion: full study feasible ~, Three distinct, highly integrated studies desiglJ~d SH ELL-MCCLU RG-06S422 C") Insert quote from Dr. Wong re: opportunity to conduct rare research in China 24 SH ELL-MCCLU RG-06S423 Rare Opportunity i::~:.::~:i Unique data set i:~:.::~:i Technological advances ::~I:I:~: Early, consistent detection and diagnosis of leukemias and related diseases in Shanghai :~:~:.:~: Identification of more sensitive benzene exposure biological markers :::::::::!::::::: Convergence of company and local Shanghai research interests 25 SH ELL-MCCLU RG-06S424 Shanghai Partners Ct Fudan University Medical Center f) Institute for Public Health Supervision Shanghai Public Health Bureau .;:~t~3t::;.;~;~lIn;~l~;;:;: Shangha-I Hematology Soc-Iety Shangha-I Pathology Soc-Iety;:;~:::;tmlf}Mt;:r:~;'. ~) Shanghai Municipal Centers for Disease Control and Prevention 26 SH ELL-MCCLU RG-06S42S SHS Hospital Partners Changha-I Hosp-Ital;:~:::~:;,'~:::~:i:~:~:::;' Changn-Ing Central;:~:::~:;,'~:ti:~i~:::;' District Hospital ::~:~:~:~:: Changzheng Hospital :i:::::::::::i: First Municipal Hospital ;~tf:\~~~~:::::::;;;' F-Ifth Mun-Ic-Ipal Hosp-Ital ;~tf:\~~~~:::::::;;;' S-Ixth Mun-Ic-Ipal Hosp-Ital ;~ttt:~~~~:::::::;;;' N-Inth Mun-Ic-Ipal Hosp-Ital Huadong Hosp-Ital;;:f\t~~~~:::::::;;;' ::~:;.~::i: Huangpu Central District Hospital Huashan Hosp-Ital;~f}t,~::::::::::::., Re nJ- HosPta I~(t)~;':~~:::::=!;;;: -I -I Shuguang Hosp-ItalAff:~;':~~:::::=!;;;: T-Ielu Hosp-Ital::WJ~::;~:::\::::::::., TongJ--1 Hosp-Ital;~f}t,~:::\::::::::., X-Inhua Hosp-Ital;~f}t,~::::::::::::., Zhongshan Hosp-Ital~(t)~;':~~:::::=!;;;: 27 SH ELL-MCCLU RG-06S426 Sino-U.S. Joint Clinical and Molecular Laboratory c~> Insert pictures of laboratory under construction and when complete :~::iwU~:t: V-I rtua I la b tou r?_ 28 SH ELL-MCCLU RG-06S427 Benzene Basics What Benzene-IS',t:~t~:if}~tl:r"r 29 SH ELL-MCCLU RG-06S428 What is Benzene? C~) A colorless, volatile, flammable liquid with a sweet aromatic odor; c") A natural component of many substances including crude oil; v.;:~r:.:t~::; A by- product of combust-IonI c") A chemical building block; and .) One of top-20 most-produced u.s. chemicals 30 SH ELL-MCCLU RG-06S429 Benzene Uses ::~I:I:~: Benzene is a basic petrochemical building block, widely used in the manufacture of products such as: ::::g:::: Dyes and laundry detergents Lubr-Icants:tit::::::::::: I:::!I Nylon and synthetic fibers (carpet, clothing) ::::::::I Pharmaceuticals Pest-Ic-Idesr)I::::::::::: I::::I Plastics and resins ::':: Some types of rubbers (tires) 31 SH ELL-MCCLU RG-06S430 Benzene Uses Ct Element of crude oil; found in small amounts in petroleum products Ct As a chemical building block, is transformed in the manufacturing process Eliminated:::::1:1:1'1:::1:::: as an unconverted additive to solvents and adhesives 32 SH ELL-MCCLU RG-06S431 Existing Benzene Knowledge tl Conclusions pre-1997 ~, U.S. Regulatory Interpretation t) Recent Epidemiological Studies Co) Challenges Observat-Ions on EX-Ist-Ing SC-Ience:tf}!:::t::;;~;l;!l;~;~:::: 33 SH ELL-MCCLU RG-06S432 Epidemiology Conclusions pre-1997 :::::::::!::::::: Acute Myelogenous Leukemia (AML) associated with benzene ::,:: No risk at exposures < 1ppm I:,:::::: Clear risk at exposures > 20 ppm :!:::{!:! Insufficient data at 1-20 ppm to assess risk :~::I:i~: Some steps are not dose-dependent and are governed by a threshold mechanism :::::::::!::::::: All steps required for induction of cancer have not been determined 34 SH ELL-MCCLU RG-06S433 u.s. Regulatory Interpretation co Regulatory decisions based on no- threshold assumption :i:i:!:i:i:i~ More research needed to assess threshold assumption 35 SH ELL-MCCLU RG-06S434 Research Challenges Ct Accounting for multiple exposures Ct Addressing confounding factors Ct Exposure estimates C,) Accuracy of medical diagnosis c") Analysis of results (case numbers, exposure range, etc.) 36 SH ELL-MCCLU RG-065435 Recent Epidemiological Studies Ct National Cancer Institute Shanghai Study (NCI) - case-control study published in 1997 iiii:;:::iiii Benzene associated with AML and Non Hodgkin's Lymphoma (NHL): unusual association with a non-AML cancer II:Il Study design did not add to understanding of threshold (lowest exposure group was 10 ppm or less) 37 SH ELL-MCCLU RG-06S436 Recent Epidemiological Studies C. Australian Institute of Petroleum's (AlP) Health Watch Study - case-control study released in 2001 :~:::~: Association with all leukemias, including chronic lymphocytic leukemia ::::::H::::; No association with NHL or multiple myeloma 38 SH ELL-MCCLU RG-06S437 Observations on Current Science Ct No definitive epidemiological evidence to define a th reshold :::::1:1:1,,1::1:1:; NCI and AlP studies conflict with earlier studies by associating benzene exposure with non-AML cancers Ct SHS designed to quantitatively address these issues 39 SH ELL-MCCLU RG-06S438 SHS Elements Ct Case Control Study :ir~}t~:~~tt~i1/?' D-Isease Progress-Ion Study Molecular Ep-Idem-Iology.,::mt:t~:~.'~:;~mil;m;::~; Qua I-Ity Sc -I ence,:;~:::f;:m1fJMt~:r:~:'. :~:iI:!:I:i; Scientific Review Panels Cu rrent Status.:;::;~~ltI~r3~t;:~l:~r.' 40 SH ELL-MCCLU RG-06S439 Specific Study Goals :~i:~:I:~:i:~ Understand relationship, if any, between benzene exposure and development of specific hematopoietic diseases: AA, MDS, AML and NHL :::::i::::: Causation of specific diseases/subtypes i:nIi Mechanism of disease progression iIiIi Dose-response relationships iIl':Ii Identification of cofactors and confounders iI!':Ii Identification of biomarkers of exposure and disease progression 41 SH ELL-MCCLU RG-06S440 Study #1 - Case Control Study ::~:I:~::i Traditional epidemiology study to determine risk of AML, and potentially NHL, among benzene exposed workers :i:~:I:~::~ Data collected will allow analysis of other causal factors for NHL ~:~::I:~:i: Estimate 4 to 5 years to obtain 450 AML and 450 NHL patients into study :i:~:I:~::~ Improved exposure assessment based on historical and concurrent workplace monitoring and questionnaire 42 SH ELL-MCCLU RG-06S441 Study #2 - Disease Progression !:~:~:I:~:~ Prospective study on relationship of non-cancer bone marrow disease and benzene-induced AML :lE:::: Is benzene-induced AML different from spontaneous AML by unique cellular markers? i1E::i: Does AML involve a progression through one or more non-cancer states? !:~:~:i:~:~: Research methods: questionnaires, interviews, review work histories; examine blood, breath, urine; study/evaluate potential biomarkers 43 SH ELL-MCCLU RG-06S442 Study #3 - Molecular Epidemiology !:~:~:I:~:~ Prospective study to establish quantitative relationship between exposure and effect :;g:~: Do low benzene exposures cause blood effects? :;:{:: Is there an association of blood effects and genetic susceptibility? :(I:;::::: Do biomarkers of exposure accurately reflect workplace exposures? :~:~:I:~::~ Healthy workers at sites with varying levels of benzene exposure will participate; extensive lab work, including genetic tests, will be conducted 44 SH ELL-MCCLU RG-06S443 Qualify Science :~:!.:~::~ All protocols reviewed and approved by external Institutional Review Boards (IRB's) :!:::=:I: Govern use of human subjects :;:: u.s. and China independently ::~t:t~::'~t~~~:1:i~~::::' Shangha-I Health Study panels t:::I: International Ethics Expert Panel ::::i{::: International Scientific Expert Panel 12 members 6 scientific disciplines :!:::=:I: Involved during entire project 45 SH ELL-MCCLU RG-06S444 Scientific Review Panels General Toxicology and Biochemistry Epidemiology Statistics Dr. Jerry M. Rice, ( Chair), IARC (Retired) Dr. Helmut Greim, Technical U. of Munich Dr. Nancy Mueller (Vice Chair), Harvard U., Public Health; Dr. Harvey Checkoway, WA U. Dr. Howard Rockette, U. of Pittsburgh Industrial Hygiene Dr. John Cherrie, Aberdeen U., Inst. Of Occ. Medicine; Dr. Robert F. Herrick, Ha rva rd U., Pu bl ic HeaIth Hematology Genetic Toxicology Ethics Review Panel Dr. Richard Larson, U. of Chicago Medical School; Dr. Mark Minden, U. of Toronto Dr. Li Guilan, Chinese Academy of Preventive Medicine; Dr. Richard Albertini, U. of VT, College of Medicine Dr. Baruch Brody (Chair), Baylor College of Medicine; Dr. Xu Zong-Liang, Fudan University Dr. Juhana Idanpaan-Heikkila, World Health Organization 46 SH ELL-MCCLU RG-06S44S Current SHS Status i:~:!.:!:~:i State-of-the-art laboratory constructed on Fudan University campus I::::I Sustainable technology transfer an important project design component I:'i::~: Built according to international standards I:':::::: Lab will support the project, Shanghai medical community and remain at Fudan Technology transfers::::::i::!i:::::: :~:g:~:~ Chinese staff receiving training at University of Colorado :::::=t::: U.S. researchers working with Chinese colleagues and government officials to finalize methodologies, questionnaires, etc. 47 SH ELL-MCCLU RG-06S446 Scientific and Ethical Review Status ::;::: Fudan University IRB - final approval Nov 01 ::;::: External International Scientific Review Panel - final approval Jan 02 :~::.:~:~ External Ethics Review Panel - final approval Feb 02 ::~:I:~:: University of CO IRB - final approval May 02 ~::~:~::~:i Applied Health Sciences - final approval 02 48 SH ELL-MCCLU RG-06S447 SHS Projected Timeline :::;:: Questionnaire development, pilot testing in progress, 2002 ::;::: Key laboratory personnel trained, 2002 ,~:::iiftit. Laboratory complete early 2003 :~:~:.::~:i Case recruitment begins - 1st quarter, 2003 :1,:::;::::: 1600 benzene exposed workers, 400 controls :1,::=;:::: Time necessary to identify qualified patients :;;:'f,:::: Length of study may be extended if required ,Laboratory open-Ing.~::::)}i:i::: spr-Ing 2003 t:~:;::~::i Research, analysis expected 2003-2007 :~:~:.::~:i Results published upon project completion 49 SH ELL-MCCLU RG-06S448 SHS Sponsors 50 SH ELL-MCCLU RG-06S449 Who is Sponsoring the SHS? :~:~:!.:~::~ A consortium of petroleum and chemical companies concerned about understanding the human health effects of benzene :i:H:!:! British Petroleum, ChevronTexaco, ConocoPhillips, ExxonMobil, Shell :In:::: Other members being recruited :lI,::::: American Petroleum Institute, project administrator ~:~::.!:~: Individual company product stewardship and corporate responsibility programs 51 SH ELL-MCCLU RG-06S4S0 Why Industry Sponsors? SHS goal to provlde an accurate';~:::~~i~i~(~:j1}:i:~:~::;:.' understanding of how benzene works on a molecular level in humans :If:::::: Advanced understanding of benzene-induced disease could lead to development of effective disease prevention strategies ::;.:: Would allow a more finely calibrated assessment of potential health effects !:!::;;::!:! Provide best protection for workers and public 52 SHELL-MCCLURG-065451 Why Industry Sponsors? C~) Worldwide, benzene occupational exposure regulatory standards vary widely I:::I~ O.5ppm in Malaysia; 1.Oppm in U.S.; lOppm in Japan :~;:::~: American Conference of Governmental Industrial Hygienists recommends O.5ppm c") Industry has long sponsored benzene research 53 SH ELL-MCCLU RG-06S4S2 SHS Funding Structure 54 SH ELL-MCCLU RG-06S4S3 SHS Funding Structure :t::::::::: $22.8 million program total for all costs over 5 years I:;'I: $16.5 million confirmed as of October 2002 :I;:~:~: Current funding through October Q3 03 :::::::::1::::::: Costs projected to be highest during first yrs. ::;::: Payment scheduIe :Ii:!:!: August 2001 I:;{:!: January 2002 I:;'I: August 2002 :IiI: August 2003 I}I! August 2004 August 2005:::::!::::::: 15% 15% 25% 15% 15% 15% 55 SH ELL-MCCLU RG-06S4S4 SHS Funding Structure :~:~:I:~::~ Funding shares determined by size and sector ::~t}t:.'~::~~~~~:1:i~~::;:' Formula used to asslgn 1 to 3 shares ::;.:: Refiners: 1 to 3 shares based on u.s. capacity :IiI: Chemical companies: 2 shares iIiIi Other companies: 1 share ::~:!:~::~ One share currently equals $1.5 million 56 SH ELL-MCCLU RG-065455 SHS Funding Structure D-Irect costs;::fJt:;:~tf~~i~~::;: ::::g:::: Data collection and analysis with procedures to protect pri-vacy; t:{::: Procedures and training for data collection in participating clinics; :::: Constructing, training, staffing state-of-the-art hematology laboratory; :::;:'i;:::: Laboratory operations for research and clinical tests; and I:':;;::: Operations for 5 years estimated to identify study cases i:~:!;i!:~:i Administrative costs ::{: Internal and external communications and coordination; :;:{: API project administration, travel; off-site meetings 57 SH ELL-MCCLU RG-06S4S6 Conclusions 58 SH ELL-MCCLU RG-06S4S7 Conclusions ~:~:I:!:I~:: PRESENTER: SELECT AUDIENCE .:.:.:.:i~~~}t~~~i Genera I ~:;!::~:i Recruitment - Funding Recru-Itment - Techn-IcalItr:::::;:~:~ :~:;:;: 59 SH ELL-MCCLU RG-06S4S8 Conclusions (") Study will advance benzene science Sponsors fund-Ing study.:tl}tt'::;;~t[}l~~::;: Product stewardship:iii:=:!::i:ii :ii;:=ti:i: Corporate social responsibility goals (.) Anticipate results published 2007/8 .) Results will add to accepted body of scientific resea rch on benzene i:I::"::::i:! Referenced by government, industry decision-makers 60 SH ELL-MCCLU RG-06S4S9 Additional Sponsors Needed C") Responsibility to understand the health impacts of your products c") Commitment to worker health, safety ::i:i:!il:i~ Need for most advanced science possible 61 SH ELL-MCCLU RG-06S460 Technical Committee Membership C") Annual meetings with investigators, sponsors 62 SHELL-MCCLURG-065461 Terms, Sources and Resources 63 SH ELL-MCCLU RG-06S462 Terminology ::iiilil:i::::iliii:~AA ::::iili:i:!:lii:::;AML B-10m arke r.:t:~:}t:,:~;;t1tr:' EP-I dem-I alogy.::if)t~:.::;mfi~;m;::' H-Istology.:.i:li:~i~~~:f~l~t~:i:~f.: NHL::ili:!:i:ili:~ 64 SH ELL-MCCLU RG-06S463 Acronyms :~::.::~: API - American Petroleum Institute :~::i:::~: AlP - Australia Institute of Petroleum :~::i:i::~: IRB - Institutional Review Board :~::.:::~: CAPM - Chinese Academy of Preventive Medicine :t::::::::: IPHS - Institute for Public Health Supervision (China) :~::.::~: NCI - National Cancer Institute (U.S.) :~::i:::~: SUJCML - Sino-U.S. Joint Clinical and Molecular Lab :~::i:i::~: SMCDCP - Shanghai Municipal Center for Disease Control and Prevention :~::.::~: USEPA - U.S. Environmental Protection Agency 65 SH ELL-MCCLU RG-06S464 Sources i:~:!:~::i American Council of Government Industrial Hygienists :~:~:I:~:~ Agency for Toxic Substances and Disease Registry ToxFAQs, U.S. Department of Health and Human Services ~:~:I:~::~ American Petroleum Institute i:~:!:~::i International Agency for Research on Cancer :~:~:i:~:~: United States Environmental Protection Agency :~:~:I:~:~ University of Colorado Cancer Center, Denver, CO 66 SH ELL-MCCLU RG-065465 For More Information Cm'Template: Add your and your team's contact information here. :::::i::::;::::::: Lorraine Twerdok, BHRC Administrator 202.682.8319i:i::i,:i::i:i Twe rd kl@ apl. rg0i!i!:;:::::!i!i 0 67 SH ELL-MCCLU RG-06S466 For More Information :::~:- i:[i:';:i:;~- :~~~~~~~~~~~~~~~ee i!i::::!::!i!i patrickbeatty@chevrontexaco. com t Don Burnett, Chair, Oversight Committee ~!:,:~~ burnetdm@bp.com .: :'. B-II Fri-c k'.;;;::;:;fm=:':{:l:;~;:~l:r:::;, I fr-Ick@ap-Iorgr:.}~ ~~:t::::~:~ f) Lorraine Twerdok, BHRC Administrator ~!:.::~~ twerdol@api.org 68 SH ELL-MCCLU RG-06S467 DRAFT AGENDA DOWNSTREAM COMMITTEE American Petroleum Institute Wednesday, May 12,2004 - 8:00 a.m. - Noon CT- Houston, TX 8:00 a.m. 8:05 a.m. 8:30 a.m. 9:00 a.m. 9:45 a.m. 10:15 a.m. 11:00 a.m. 11:30 a.m. 11:35 a.m. 11:45 a.m. Noon Continental Breakfast 7:30 a.m. Introductory Remarks Presentation by a Member Company on Initiatives to Improve Environmental and Safety Performance National Energy Bill (Attachment 1) Status and strategies for the future Action: Provide guidance on further advocacy efforts NAAQS (Attachment 2) Review EPA's final rule implementing the 8-hour ozone standard Results of April 23 NAAQS strategy discussions among API committees ofjurisdiction Action: Provide guidance on advocacy goals and objectives Fuels Committee Activities (Attachment 3) Review EPA's non-road diesel rule Northeast states initiatives: low sulfur heating oil, regional fuels NAAQS implementation issues for fuels Auto's Top Tier Gasoline Program Action: Provide guidance on strategies to address the above API Health Effects Subscription Research Programs (Attachment 4) Overview of API Programs Status of Shanghai Health Study (China Benzene) 0 Potential business impacts 0 Use in advocacy API Involvement in International Activities (Attachment 5) World Petroleum Congress IPIECA (global climate, corporate reporting, transparency, corporate social responsibility) UN Partnership on Clean Fuels and Vehicles Update on Strategic Communications Steering Committee (Attachment 6) Next phase: defining an envisioned future Marketing Committee Activities Update (Attachment 7) Gasoline supply and communications activities, underground storage tank legislation, SPCC litigation Other Business (Attachment 8) Review 2005 Budget Time Line and 2005 Major Issues Adjournment Gary Heminger Chair, Downstream Committee TBD Patricia Richards Chair, Transportation Fuels Committee TBD Mike Leister Chair, Fuels Committee Ed Murphy Downstream Group Director Patsy Clegg Chair, Benzene Health Research Consortium Oversight Committee TBD Pamela Beall Marathon Ashland Mary Ellen Peters Chair, Marketing Committee Ed Murphy Gary Heminger SH ELL-MCCLU RG-06S468