Document napGKMX0gQ8EvR1Ro81mwMr2

From: Sent: To: Subject: Cagen, Stuart SZ SCC Wednesday, January 24,2001 3:18 PM Clegg, Patsy M SCC-CHSE-PC; Tsai, Shan SP SHLOIL-SPS FW: Benzene Follow Up Flag: Due By: Flag Status: file in china study Follow up Monday, July 02, 2001 5:00 PM Flagged -----Original Message----- From: Beatty, Patrick (PWBE) [SMTP:PWBE@chevron.com] Sent: Wednesday, January 24, 2001 2:33 PM To: 'arschna'; 'Cagen, Stuart SZ SCC' Subject: RE: Benzene I have spoken to Otto and emphasized to him that his exposure experts need to coordinate with Tom Armstrong to ensure that we have a consistent approach that will not invite criticisms when the studies are reported in the literature. I believe that he is amenable to that. I agree with Rob that we have adequate technical expertise associated with the current PI's to perform any require dose-response modeling. I would support having external expertise on the Science Advisory Panel to comment on their activities. Patrick > -----Original Message----> From:arschna [SMTP:arschna@erenj.com] > Sent: Tuesday, January 23, 2001 9:06 AM > To: 'Cagen, Stuart SZ SCC'; 'arschna' > Cc: Harrison, M.C. (Myron); Caldwell, Daniel J.; Russo, L.B. (Lynn); > 'Beatty, Patrick (Chevron)'; 'R. Jeffrey Lewis' > Subject: RE: Benzene > > No - there will be many IH and epi resources involved in exposure > assessment. For the disease progression and molecular epi studies, > exposure > assessment will involve several resources. First, Tom Armstrong, who has > much experience in benzene exposure estimating (principal on Canadian 10L > study; tecnical advisor to UK Institute of Petroleum and Australian > Healthwatch studies) will lead the effort. Tom will rely heavily on > resources within the Shanghai CDC, particularly Lu Wei, Zhong Zhou, > Lipiang > Bao and others. SCDC have access to all worksites in Shanghai, and we have > > toured several worksites as a team already. Tom Armstrong and Jerry Lynch > > are former colleagues and know each others' work quite well. > > I am less sure who is involved regarding the NHLlAML case control study. > However, Otto Wong, (the PI) lists Lu Wei from SCDC as a contributor, as > well as an industrial hygienist from Fudan University. Otto plans on > developing a detailed exposure assessment procedure as part of the > investigation itself. I am sure that Otto knows the importance of a > detailed and accurate exposure assesment procedure. > SH ELL-MCCLU RG-0679S7 > In addition, there will need to be exposure assessment expertise as part > of > the Scientific Advisory Committee. Persons like Jerry Lynch, Nurt Esmen, > Bob Herrick etc. should be considered. > > As for dose resposne modelling, I beleive it is too early to budget for > that. We are not sure what the study will show, and therefore whether > modelling is appropriate. However, our biostatistician is very adept at > modelling and has alot of experience in this area. Since we plan on using > > him in the study, if modelling is indicated, it can be performed by him. > Otto Wong is also a biostatistician, and has previous experience in the > area as well. However, a detailed modelling exercise would not be > covered, > but I suggest we could add that at a later date if it is indicated. > > Please come back if this raises more questions! > > Rob > > > On 01.23.2001 10:27 AM, Cagen, Stuart SZ SCC > [SMTP:SC724012@MSXSCC.SHELL.COM] wrote: > > Rob: > > Thanks for the reply. More questions: > > 1) are the investigators on their own for the exposure assessment? > Jeff > > and I know that guys like Jerry Lynch and others were valuable to the > UAB > > study. > > 2) is someone lined up for the dose response modeling? The butadiene > folks > > used Bob Sielken. > > Thanks > > Stuart > > > -----Original Message----> > > From:arschna [SMTP:arschna@erenj.com] > > > Sent: Tuesday, January 23, 2001 9:00 AM > > > To: 'Cagen, Stuart SZ SCC' > > > Cc: Harrison, M.C. (Myron); Caldwell, Daniel J.; Russo, L.B. > (Lynn); > > > 'Beatty, Patrick (Chevron)'; 'R. Jeffrey Lewis' > > > Subject: RE: Benzene > > > > Stuart - a fundamental aim of the three studies on benzene in China is > > for > > > > use in risk assessment. As you're well aware, for epidemiology > studies > to SH ELL-MCCLU RG-067958 > > > > be useful in dose response assessment (rather than simply hazard ID), > > > quantitiative estimates of exposure, as in the UAB/SBR study, are > > > necessary. This permits calculation of slope factors, etc. This is a > > > feature of all three epidemiology studies being proposed in Shanghai, > and > > > exposure estimating may even be more precise than the UAB studies, > since > > > they will be done on individuals (with access to workplace records), > > > rather > > > than broader worker groups as in the SBR study. Slope factors are only > > > appropriate for clear, positive findings, however. For negative > studies, > > > adequate power must be present, so that the epidemiology studies can > be > > > used as "consistency checks" in risk assessment. This is also a > feature > > > of > > > all three studies. > > > > However, benzene risk assessment is a bit more complicated. Before > > > regulators move away from linear, no threshold assumptions, > mechanistic > > > information is necessary. With benzene, it is difficult, because > there > is > > > > no good animal model. Shanghai is one of the few places which has both > > the > > > > technological sophistication and degree of exposure necessary to > develop > > > reliable mechanistic insights on benzene-induced leukemia and related > > > blood > > > disorders. The data should prove to be most valuable in understanding > > > whether precursor conditions are necessary, whether gross chormosomal > > > alterations are necessary, a precursor, or a byproduct of exposure, > etc. > > > etc. This mechanistic emphasis, in my mind, is probably the most > valuable > > > aspect of the study, because there is no reason to move away from the > > > pliofilm-derived risk estimates without mechanistic insights that > suggest > > > benzene's carcinogenicity is not the simple result of a one > > > hit/adduct/cancer mechanism. > > > > I hope this helps. There are, of course, other good reasons for > moving > > > forward with the studies related to product stewardship which I did > not > > > mention. > > > > Rob > > > > > On 01.19.2001 10:51 AM, Cagen, Stuart SZ SCC SH ELL-MCCLU RG-067959 > > > [SMTP:SC724012@MSXSCC.SHELL.COM] wrote: > > > > Jeff/Rob: > > > > This has probably already been discussed but please humor me - as a > > new > > > > comer to benzene - so I can have some closure. > > > > The issue may have been previously developed or may be discussed > next > > > week > > > > at the benzene consortium meeting but I would like to know how the > study > > > > can > > > > be optimized for benzene risk assessment purposes. What I have in > mind > > > is > > > > to emulate the risk assessment success that we anticipate as a > result > of > > > > the > > > > UAB butadiene study. The concept is that a combination of a robust > epi > > > > study and a world class exposure assessment can lead to a ready to > use > > > > regulatory (EPA) risk assessment. I realize there are special > > > additional > > > > attractions to the benzene China study, but I don't necessarily have > > the > > > > confidence in the exposure assessment leading to a useable risk > > > assessment > > > > for this study as I did for the UAB BD study. > > > > Is the question comprehensible? Can either of you answer this or > > > reassure > > > > me in other ways ? > > > > Thanks > > > > Stuart > > > > > SH ELL-MCCLU RG-067960