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Margin of Exposure

Carol Fry cafry at toolcity.net
Sun Aug 10 13:37:28 EST 1997


Chuck Miller wrote:
> 
> Hi Patrick,
> 
> You wrote......
> 
> >I was wondering what the general consensus is on the new EPA cancer
> >guidelines Margin of Exposure non-linear default approach? Do you find it
> >lacking in detail and rather uninformative?
> 
> Is the document below what you are discussing? If so, then yes it is pretty
> nonspecific about lots of things. But then again, such is the state of the
> art in risk assessment. It is a tall order to predict adverse effects of
> chemicals from sparse, erroneous, or nonexistent data. Perhaps you could
> give us your views on nonlinear dose-response assessment and margin of
> exposure.
> 
> This document was obtained from http://www.epa.gov/science1/ehc0297.htm
> 
>                         Environmental Health Committee
> 
>                        and the FIFRA Scientific Advisory Panel (SAP)
> 
>                       U.S. ENVIRONMENTAL PROTECTION AGENCY
> 
>                            SCIENCE ADVISORY BOARD (SAB)
> 
> MINUTES OF MEETING: February 13-14, 1997
> 
> PURPOSE: The main purpose of the meeting was to discuss and review EPA's
> Proposed Guidelines for Carcinogen Risk
> Assessment.
> 
> LOCATION: The meeting took place at the Holiday Inn Georgetown Hotel,
> Washington DC 20007 and was announced in
> the Federal Register for January 23, 1997 (Vol. 62, No. 15, page 3510)
> (Attachment A).
> 
> PARTICIPANTS: SAB Members, Consultants, Federal Experts, and Staff: Dr.
> Emil Pfitzer, Chair, Drs. Charles Capen,
> Adolfo Correa (Day 2 only), Kenny Crump, Ernest McConnell, Frederica Perera
> (Day 1 only), Henry Pitot (Day 1 only),
> James Swenberg, Mark Utell (Day 1 only), and Lauren Zeise; Mr. Samuel
> Rondberg, Designated Federal Official (DFO) and
> Executive Secretary to the EHC, and Ms. Mary Winston, Staff Support
> Secretary to the Committee. The Committee Roster
> (incorporated as Attachment B) lists the EHC attendees and their
> affiliations. A "Sign In" sheet listing other attendees is
> incorporated as Attachment C.
> 
> Six members of the public had registered to make statements to the Meeting
> per the invitation in the Federal Register and are
> identified in the Agenda (Attachment D). During the course of the meeting,
> several other members of the public did take the
> opportunity to make brief statements or comments as part of the informal
> discussions involving Committee Members and/or
> Agency staff.
> 
> Dr. Ellen Sibergeld, who had planned to attend the meeting as a member of
> the Committee (and who appears on the
> previously printed Agenda) could not attend; Dr. Silbergeld did address the
> group briefly during the first day of the meeting
> concerning
> 
> the issue of departures from default values -- the issue to which she had
> earlier been assigned as lead discussant.
> 
> SUMMARY: The meeting followed the Agenda with some minor rearrangements and
> deviations in timing to accommodate
> Member's schedules.
> 
> The meeting opened at 9:00 AM with brief administrative comments by the
> Chair and by the DFO. Each Member of the
> Committee then presented statements as to their affiliations and any
> previous involvement in issues related to topics to be
> discussed or to any parties with an interest in the outcome of the review.
> No one reported any associations or activities which
> were, or which appeared to be, conflicts under current policies in so far
> as the current meeting was concerned.
> 
> Dr. Arnold Kuzmack, EPA/OW briefed the Committee on the proposed
> Carcinogenicity Risk Assessment Guidelines,
> providing a brief history of their development, and addressing the
> principle issues arising in the public comment process: Dr.
> Kuzmack's slides are incorporated as Attachment E.
> 
> Following brief dialogue with Dr. Kuzmack, six members of the public
> addressed the Committee: Dr. James Wilson,
> Resources for the Future (slides incorporated as Attachment F); Dr. Matthew
> Bogdanffy, Chemical Manufacturers
> Association (slides incorporated as Attachment G); Mr. Steve Milloy,
> Environmental Policy Analysis Network (slides
> incorporated as Attachment H); Dr. Michael Gough, Cato Institute (slides
> incorporated as Attachment I); Mr. William G.
> Kelly, Jr., Federal Focus, Inc. (slides incorporated as Attachment J); and
> Dr. M. Jane Teta, American Industrial Health
> Council (slides incorporated as Attachment K).
> 
> In addition, the Committee was addressed by an invited speaker, Dr. Mel
> Anderson. Dr. Anderson reported on the findings
> an an Expert Panel convened by the International Life Sciences Institute to
> review the draft Guidelines. His slides are
> incorporated as Attachment L.
> 
> The Committee then turned to discussion of the specific issues embodied in
> the Charge for the meeting. The entire
> proceedings of the Committee are recorded in a transcript, incorporated as
> Attachment M. A brief summary of the
> Committee's major findings on the Charge issues follows.
> 
> a) General: There was general support within the Committee for the proposed
> guidelines. The EHC found that the
> Guidelines were a significant step forward for the Agency, but will
> recommend some rewording in several areas.
> 
> b) Hazard Classification: EPA had proposed 3 broad
> descriptors--"known/likely", "cannot be determined" and "not
> likely." The EHC supported the importance of having a narrative to provide
> the evidence for carcinogenicity. However, it was
> not possible to reach a consensus in the meeting for a list of descriptor
> terms that would provide a heading for the narrative. It
> was clear that the "known/likely" descriptor was meant to be two different
> descriptors, but several members felt that the
> descriptor "likely" was not a good term. There was some support for the 8
> descriptors proposed by Ashby, et al., which is
> basically an expanded IARC classification. Concern was expressed that the
> EPA's list of approximately 11
> descriptors/sub-descriptors was too detailed. The discussion ranged from an
> expression of using only a narrative without
> descriptors to an expression of narrative with a list of 3 to 8
> descriptors. There was no consensus at the meeting on what the
> descriptors should be.
> 
> c) Defaults/Mode of Action: The EHC was in agreement that deviations from
> default assumptions must be based on
> strong scientific evidence. There was extensive discussion about the
> problem of defining the "strength" of scientific evidence,
> with agreement that additional guidance was important. Specifically, there
> were expressions of concern that, without
> additional guidance, mode-of-action as a basis for deviation from default
> would be misused. It was requested that the
> guidelines re-emphasize that when there is uncertainty the decision should
> favor the protection of the public's health. There
> were expressions of concern about the use of the term "default." Suggested
> alternatives were "in the absence of information
> use the most conservative option" or "inference guideline"; a term
> suggested back in 1983.
> 
> d) Dose-Response: EPA suggested dividing the dose-response curve into an
> observed range where data exist, and a range
> of extrapolation where there were no data -- using the lower bound on the
> 10% cancer incidence as a point of departure for
> extrapolation to lower doses. Cancer precursor data (e.g., hyperplasia
> incidence, hormone levels) might also be used. EPA
> also proposed biologically based dose-response as the preferred
> extrapolation technique, with linear and nonlinear defaults.
> 
> The Committee supported the division of the dose-response range and the
> proposal to use the lower bound on the 10% tumor
> incidence. There was not uniform endorsement of the use of precursor
> information for quantitative assessment however,
> although it could be used qualitatively.
> 
> e) Margin of Exposure Analysis: The EHC discussed the Agency's proposal to
> use a margin of exposure analysis for
> nonlinear dose response assessment. It was felt that this topic needed the
> addition of case studies to better illustrate its use,
> and there was no consensus on the advice to be given to a risk assessor on
> the magnitude of an appropriate MoE. The EHC
> also requested further wording on how the Agency would use peer review in
> the process of deciding alternative approaches.
> 
> f) Human Data: The EHC understood that dose-response data will often be
> deficient in studies with humans. It was agreed
> that wherever possible information on dose-response should be used, but
> that decisions would necessarily be on a
> case-by-case basis. It was noted that it will often be important to have
> access to raw data for the best utilization of human data
> for risk assessment, and that EPA should request this. The EHC agreed that,
> because of apparent misunderstandings, it was
> important to clarify that statistical significance would be used in judging
> human data. However, it was considered that
> statistical significance should not be a strict criterion for causality,
> but that it should be coupled with reasoned judgment. The
> Bradford-Hill recommendations for judging chance should used, but as
> guidelines not as criteria.
> 
> g) NRC Recommendations for Tumor Data Analysis: The EHC considered that
> neither the NRC approach nor the
> Agency's proposed approach should be used without modifications. It was
> agreed that the summing of tumor types was not
> scientifically appropriate. However, the occurrence of tumors at different
> sites should be recognized in the weight of evidence
> approach. The decision to sum potencies for independent tumor types should
> be limited to a case-by-case decision. Since
> summing of tumor types or summing of animals with tumors can often "swamp"
> the critical factors for risk assessment, it
> was considered that this should not be a routine practice.
> 
> h) The EHC agreed that the Agency should take susceptibility factors into
> account when they are known. In particular
> concern for children and individuals with polymorphisms should be evaluated
> as potential populations at risk. There was
> considerable discussion regarding a potential generalized uncertainty
> factor for linear extrapolations to human populations;
> there was no consensus for a specific number.
> 
> Following a brief discussion of report preparation, Dr. Pfitzer adjourned
> the meeting at 1:06 pm.
> 
> Mr. Samuel Rondberg
> 
> Designated Federal Official
> 
> Dr. Emil Pfitzer
> 
> Chair
> 
> ENCLOSURES
The exposure to toxic waste by the epa and the cdc is an abomination to
the American people. I was exposed to carconigens and used as a guiney
pig and have never had any help from the DEP, EPA, CDC ,Health Dept.
Everything has been swept under the carpet.  My lawyers are giving me a
royal s-------. No one seems to care. I am still living in a polluted
house where we have carried our drinking water since 1988, can only take
a bird bath because the toxic waste is out of site and no one will help
us .  So this is America huh!  I pay 1200$ a year taxes for this this is
bull crap



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