2                 ON TOXIC AIR CONTAMINANTS
       13                 TRANSCRIPT OF PROCEEDINGS
                           1200 University Avenue
       14                   Riverside, California
                        Wednesday, November 11, 1998
       15                         9:00 A.M. 
       23   REPORTED BY:  
            Katherine Gale, 
       24   CSR 9793 
            Our File No. 1-50626


        1   MEMBERS PRESENT:  
        2          Dr. John Froines, Chairman
        3          Dr. Craig Byus
        4          Dr. Gary Friedman
        5          Dr. Anthony Fucaloro
        6          Dr. Stanton Glantz
        7          Dr. Peter S. Kennedy
        8          Dr. James Seibert
       11          MR. WILLIAM LOCKETT, Deputy Ombudsman,
                   Northern California
                   MR. PETER MATHEWS, Office of Ombudsman
            HAZARD ASSESSMENT:  
                   DR. GEORGE ALEXEEFF, Deputy Director of
       16          Scientific Affairs
       18          Mr. Paul Gosselin, Assistant Director
       19          Mr. Tareq Formoli, Associate Environmental
                   Research Scientist
                   Dr. Ruby Reed, Staff Toxicologist
                   Mr. Kevin Kelly, Associate Environmental
       22          Research Specialist            

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1                        PROCEEDINGS
        2                         * * * * *
        3                 DR. FROINES:  I guess we'll call this
        4   meeting to order and thank Jim Seiber for replacing
        5   me last month while I was busy with MTBE which is now
        6   complete.  
        7                 And so we're going to change the agenda
        8   a little bit.  What we'd like to do is to start out
        9   talking about the workshop.  And the reason for
       10   changing the agenda slightly is just because Stan and
       11   Kennedy and Peter aren't here and that this is that
       12   we might be able to dispose of readily, fairly
       13   quickly, and then perhaps the others might be here
       14   for the substance of discussions.
       15                 So I wrote a memo which everybody
       16   received, and my proposal was that this workshop be
       17   similar to the workshop we had at UCLA in March, and
       18   that is that it be an SRP workshop in which we work
       19   closely with DPR to put it together but it basically
       20   be our responsibility to organize; that we would
       21   define the agenda and that we would define the
       22   speakers in collaboration with DPR.  But this would
       23   be a -- in a second -- a second scientific workshop
       24   sponsored by the SRP.  And I don't know if there was
       25   discussion about that at the meeting.

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1                 DR. SEIBER:  Well, I think our
        2   supposition from the beginning was that -- as I
        3   recall, was that it would be a joint undertaking. 
        4   And that's why I think the -- it's introduced by both
        5   the ARB and the SRP panel chair.  
        6                 So I guess the thing we would need to
        7   probably discuss or consider is whether it's only --
        8   you know, what involvement of the two parties as it
        9   takes place.  
       10                 And we've asked DPR to come up and step
       11   up to the plate, so to speak, and prepare a draft
       12   which we have.  And personally I think it's a
       13   workable draft, and I think it can accomplish what
       14   you mentioned, John:  the involvement of SRP and the
       15   selection of the exact experts and specific topics to
       16   be addressed.
       17                 DR. FROINES:  I think that the one
       18   thing that -- this is a strange room, isn't it?  It's
       19   too big so that you feel like you're talking in this
       20   vacuum.
       21                 DR. FUCALORO:  We should invite some
       22   students in.
       23                 DR. FROINES:  Yeah.
       24                 DR. FUCALORO:  In today's environment
       25   they'd get half a class credit.  

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1                 DR. FROINES:  We should have all the
        2   environmental policy student's here -- right? -- so
        3   they can see how it really works in the real world.
        4                 DR. FUCALORO:  If this is the real
        5   world.
        6                 DR. FROINES:  That's right.  If this is
        7   the real world, we're all in deep trouble.
        8                 Anyway, the one thing I think is clear
        9   to me -- and I don't know how others feel -- but that
       10   Bill Lockett and I have gone around and around
       11   talking about when the meeting should occur.  
       12                 And everybody on this panel is busy. 
       13   And the one thing we want to do is have a
       14   well-organized meeting.  And so Bill was talking
       15   about a January 15th day.  And I would actually
       16   propose that we have it in February and we use
       17   December and January to organize the meeting, and
       18   that way we would be able to do a really good job at
       19   doing it.  
       20                 And I think otherwise we're going to
       21   have to plunge right in right now and put an awful
       22   lot of our time into meeting this January 15th
       23   deadline.  And I frankly think that that would be
       24   premature.  And it would not be as good a workshop, I
       25   think.  

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1                 So I would argue for some time in
        2   February that we can work out mutually with Paul and
        3   others at DPR and that we try and get everybody from
        4   the panel.  
        5                 DR. SEIBER:  Well, I certainly agree
        6   with that.  Particularly if we're going to get some
        7   top-notch experts from elsewhere in, it's essential
        8   we give them enough lead time.  
        9                 Also this is a dialogue opportunity. 
       10   The chemical companies and people with all different
       11   backgrounds would want to come and participate.  So
       12   we need to give them time to think about it too.
       13                 DR. FROINES:  So nobody disagrees? 
       14   That's okay with you, Paul?  
       15                 MR. GOSSELIN:  Yes.
       16                 DR. FROINES:  Do you want to sit up
       17   front just so you have a feeling of warmth and
       18   closeness, congeniality as it were?  
       19                 DR. SEIBER:  We thought maybe you could
       20   move your chair in the middle here.
       21                 DR. FROINES:  Might be a little too
       22   friendly.  
       23                 Anyway, the second issue about the
       24   workshop is that I do think this is a good start.  My
       25   sense is that one of the things that would be most

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   valuable is we need to look at the list of pesticides
        2   that we anticipate coming before us over the next
        3   year and add to that any other pesticides of
        4   particular relevance.
        5                 For example, just to pick my favorite,
        6   I don't know if you had a list of 12, whether Telone
        7   would be on it, but there's some interesting science. 
        8   And Telone's role relative to what happens with
        9   methyl bromide, it's clearly going to go up or down. 
       10   And so there are some other pesticides that may have
       11   constant -- may be of some significance that we want
       12   to think about.  
       13                 So if we try and define a list of
       14   pesticides that could come before this panel over a
       15   period of time, we should then look at those and try
       16   and define what are the underlying scientific issues
       17   that this panel should be knowledgeable about in
       18   order to address them.
       19                 This is a -- this is -- we have
       20   historically dealt principally with carcinogenesis,
       21   with their toxics.  And so we're in a different
       22   ballgame now.  We're dealing with non-cancer
       23   endpoints.  We're dealing with neurotoxicity.  We're
       24   dealing with clearly different approaches to
       25   evaluation.  

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1                 And it seems to me that we need to
        2   probably, as a subcommittee, define what are the key
        3   scientific questions that need to be addressed
        4   ranging from the mechanisms of delayed neuropathies
        5   and that kind of issue to how one deals with plasma
        6   cholinesterase to -- but even those are stated in the
        7   practical context.  We need an underlying mechanistic
        8   basis.  So one of the issues is to what degree do we
        9   understand mechanism which, therefore, can drive our
       10   understanding of health effects and dose response.
       11                 So it seems to me we need to define the
       12   pesticides, we need to define the underlying
       13   scientific issues, and then we need to define who are
       14   the best people to speak to those issues.  So it's in
       15   a sense a tier of three, it seems to me.  And then we
       16   can try and get them here and see where it goes from
       17   there.  So that's the kind of approach that I would
       18   think would be useful.
       19                 DR. SEIBER:  Yeah, John, one thing we
       20   talked about -- and I don't know whether we reached a
       21   resolution -- maybe we did in our own minds -- was we
       22   could separate the fumigants from all the other
       23   pesticides and maybe think about having two
       24   workshops:  just kind of a general pesticide-in-air
       25   workshop in February and then a more specific one

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   just on fumigants because they are, as you indicated,
        2   loaded with issues and may require more time than a
        3   one-day workshop.
        4                 DR. FROINES:  Well, let's take that a
        5   step further.  Maybe what we want to do is to have
        6   this body in a sense convene at a series of workshops
        7   over time on the issues of pesticides in California
        8   because it is such a major issue.  
        9                 And we can see as a way to -- as a way
       10   to not always focus on the narrow regulatory issues
       11   but to try and look at the science underlying it that
       12   would facilitate making good regulatory decisions.
       13                 MR. GOSSELIN:  Yeah, I think with the
       14   discussions my staff have had on trying to develop
       15   the workshop, the draft before you now for the topics
       16   will cover some general scientific -- compelling
       17   scientific issues that will cover a number of the
       18   pesticides that are coming before us.  
       19                 But what we also got into was that not
       20   all the topics that we're facing can be covered in a
       21   one-day workshop.  And we're looking at maybe having
       22   a follow-up one in six months.  
       23                 And you know, the whole issue that
       24   covers all of them is how do you design -- one of the
       25   issues is how do you design the appropriate

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   monitoring program to characterize exposure.  
        2                 From that, that doesn't even get
        3   into -- and this is a major issue with the fumigants:  
        4   How do you take that data and model it to create
        5   buffer zones and to evaluate on exposures.  That, I
        6   think, is going to be an important topic for maybe a
        7   subsequent workshop.  
        8                 But the whole issue on cholinesterase
        9   inhibition and those issues that will cover the whole
       10   range of pesticides does need a large amount of time.
       11                 DR. FROINES:  Well, I think you're
       12   right.  I mean, it seems to me that -- I think I
       13   understand a lot of the toxicology of these
       14   compounds.  
       15                 I think the exposure issues are really
       16   quite difficult and challenging, and so one could
       17   argue that we're going to need to put a fair emphasis
       18   into how does one address these questions, especially
       19   because theoretically we're dealing with air toxics
       20   as opposed to occupational exposures.  
       21                 Occupational exposure assessment is
       22   difficult enough because you have multiple exposures
       23   to pesticides, and people don't know how to do that
       24   very effectively.  
       25                 But here we're dealing with a cast of

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   very -- a very different situation where we're
        2   dealing with an ambient of concentrations, and
        3   they're important issues.  
        4                 So I would agree.  I think we -- I
        5   think we ought to signal the exposure as one of the
        6   key areas.  Certainly the health effects endpoint is
        7   another.
        8                 And I think what we want to do -- my
        9   only criticism of this is I think the panel does need
       10   to know -- have some information as background and --
       11   but I think we want to avoid it being too much
       12   government in a sense of describing what we do and
       13   how things are done and so on and so forth.  
       14                 But we've all been -- you know, we're
       15   getting older, so we've been through a million
       16   meetings like that where a whole bunch of people go
       17   up and say stuff that put you to sleep, and that's
       18   what we want to avoid, it seems to me.  
       19                 DR. SEIBER:  The only exception I would
       20   add to that is this Food Quality Protection Act has
       21   really turned things around, and now pesticides in
       22   air and residues in food and water, they're all
       23   looked at together.  And in the past we used to be
       24   able to partition them out and address each medium
       25   separately.  

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1                 So I hope we can have kind of -- and I
        2   thought somebody like Steve Johnson could come and
        3   give the current thinking in Washington, which is
        4   changing literally from week to week, on how to
        5   implement that act.  That would be important, new
        6   information.
        7                 MR. GOSSELIN:  But I think for the
        8   major scientific topics that were laid out, I think
        9   we were originally having an idea of having sort of a
       10   panel of experts with different perspectives to --
       11   instead of getting into sort of that straightforward
       12   presentation but get into a dialogue on the different
       13   sides and points of view on those issues, which I
       14   think is what you're talking about.  
       15                 And I think that's what we're looking
       16   for, those broader topics to actually have it maybe
       17   designed that way, to elicit some comments and some
       18   thought and dialogue.
       19                 DR. FROINES:  And there's a lot going
       20   on right now.  You know, people are -- you know,
       21   people are looking at interindividual variability
       22   much different than they have in the past, and that's
       23   going to become a major issue.  
       24                 You know, here's this paper in nature,
       25   math -- "Mice lacking serum peroxinaser, susceptible

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   organophosphate toxicity."  So genetic polymorphisms
        2   and molecular biology is now a part of what we're
        3   talking about.  
        4                 And so when we're looking at sensitive
        5   individuals, sensitive populations, all that becomes
        6   important.  And so we need to bring it to the level
        7   at which some of the science is beginning to operate
        8   at.  
        9                 And because it has clear significance, 
       10   especially when we're trying to look cross species. 
       11   And so we need to do a good job with the
       12   toxicokinetics, and then various genetic issues
       13   become even more important given different potential
       14   polymorphisms and various metabolizing enzymes.
       15                 So it seems to me that we probably need
       16   a small group which, I guess, should be Jim and me
       17   and Craig.  I read the transcript.  I know who talked
       18   the most.  So if you talk the most, you get to be
       19   part of the committee; right?  And if Gary or Tony
       20   wants to be on the subcommittee, they can volunteer.
       21                 DR. FUCALORO:  Or not.
       22                 DR. FROINES:  Or not.
       23                 DR. FRIEDMAN:  I don't feel I have the
       24   expertise in that area.
       25                 DR. FUCALORO:  I mean, that really is

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   not my area.  Right.  
        2                 DR. FROINES:  I think this is a tough
        3   one for us because we've been taught by George back
        4   there for all these years so we trust him, and we
        5   listen to him in a decent way.  Now we're trying to
        6   deal with delayed neuropathies in hens.
        7                 DR. FUCALORO:  In hens?  
        8                 DR. FROINES:  Yeah.  And we've got to
        9   figure out how to deal with that.
       10                 DR. BYUS:  Yeah, I have actually in
       11   front of me the list I got some -- a while ago on
       12   what the potential pesticides that would be presented
       13   to us in the next year, theoretically.  
       14                 And if you could -- which ones of these
       15   have not -- I think we're pretty good on the cancer
       16   endpoints in terms of health.  As you said, we've got
       17   a pretty good experience with that.  
       18                 But it's the non-cancer endpoints,
       19   especially if they are at all unusual -- even the
       20   usual non-cancer endpoints -- that you might
       21   highlight for us.  
       22                 Tell us which one of these -- without
       23   us seeing all the documents which ones have
       24   non-cancer endpoints.  Is it clearer or is it some --
       25   you know, does it require some interpretation in the

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   level of calculating NOELs and LOELs, whatever.  
        2                 And you're the experts at it.  And if
        3   you could -- on the front end, this is what I think
        4   you're saying, John:  If you can identify those
        5   difficult areas for us initially, then we could have
        6   some other -- some people come and speak to us about
        7   it, it might save everybody a lot of time and
        8   actually make a much better analysis.  
        9                 I mean, can you do that, Paul, or is
       10   that difficult to do or not?  
       11                 MR. GOSSELIN:  Yeah, I think from the
       12   dozen or more risk assessments we've gone through and
       13   completed, there is probably a finite set of
       14   compelling endpoints and things that have been
       15   driving the risk assessments that we could probably
       16   lay out and maybe give some examples.  So I think --
       17   I think that's doable.  
       18                 Not -- you know, I think as we go
       19   through, in my experience, getting risk assessments
       20   in the end, those are the questions that I'll
       21   typically ask as to the story behind the story in the
       22   risk assessment.  
       23                 But there's a lot that we have from
       24   prior risk assessments that we can actually scope out
       25   for the workshop that will cover, you know, all the

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   ones coming up.  So I think we can use our prior
        2   experience to lay those things out.
        3                 DR. FROINES:  I think Jim Seiber is
        4   right.  We need to be careful that we schedule it --
        5   we define the issues we want to talk about rather
        6   carefully so we don't try to do too much and plan to
        7   do a couple more later to cover more ground.
        8                 DR. FUCALORO:  I agree.  I think if you
        9   do too much, actually, you end up not really being
       10   very effective, and I think if you parse out the
       11   information in a reasonable rate, I think people can
       12   absorb it.
       13                 DR. SEIBER:  And again, one of the
       14   purposes of the workshop is to get community
       15   involvement.  This is their opportunity, people
       16   outside the panel and state agencies, to speak up. 
       17   So we want to make sure we save some time for that.
       18                 DR. FROINES:  Yeah.  And I think it
       19   would be good to have some industry representatives
       20   participate.
       21                 You know, on Telone there's a nice
       22   paper in the latest chemical research in toxicology,
       23   but I know that Dow is doing some work on DNA adduct
       24   formation.  So where you have active research
       25   programs going on, it seems to me to be useful to try

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   to identify.  And your folks may be aware of some of
        2   the most active work going on that would be helpful.
        3                 Who will be the lead for DPR to work
        4   with us?  
        5                 MR. GOSSELIN:  On setting up the
        6   workshop?  Lisa Ross is still the staff lead.
        7                 DR. FROINES:  So that's the person we'd
        8   call?  
        9                 MR. GOSSELIN:  Uh-huh.
       10                 DR. FROINES:  Because we're going to
       11   get down to the nitty-gritty fairly soon, I hope,
       12   where we're not just talking in loft terms about
       13   mechanisms.
       14                 MR. GOSSELIN:  Yeah.  And I would -- I
       15   mean, we'll -- you know, we're looking to have this
       16   set up and get going as quick as we can all get it
       17   together.  
       18                 But I think the draft outline here
       19   today, especially the discussion on cholinesterase
       20   inhibition and the monitoring design are two
       21   compelling issues that will cover a large number of
       22   the pesticide issues that are going to come before
       23   us.  So it might be a good starting point.  But I --
       24   a lot of people brought up other issues as important
       25   issues that I think could be the topic for future

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   workshops.
        2                 DR. FROINES:  Well, there's a lot of
        3   different issues.  My understanding -- because I've
        4   read the transcript, not having been there -- but
        5   with organophosphates, you also have to worry not
        6   only about the traditional delayed neuropathies that
        7   represent axonal damage, but you also have to be
        8   concerned with neurobehavioral changes and other
        9   chronic, long-term changes that are quite different
       10   than what you think of with organophosphate acute
       11   toxicity.  And I think that in the long run we have
       12   to pay attention to that.  
       13                 Because when we're looking at
       14   long-term, more irreversible, in a sense, effects as
       15   derived from chronic toxicity that are in some cases
       16   neural behavioral and some cases have their own
       17   well -- reasonably defined histopathology, that -- so
       18   I think that the issues with organophosphates, we
       19   would do damage to ourselves if we only saw it in the
       20   sort of traditional organophosphate mechanistic view
       21   because that's relatively reasonably straightforward. 
       22                 And so the question is -- because one
       23   of the problems has always been, you know, even with
       24   the delay neuropathy mechanistic work that people
       25   like Richardson did 20 years ago on neurotoxic

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   esterase and what's happened since then, it's still
        2   more complicated than what people have said it looks
        3   like.  
        4                 And so all I'm saying is that I think
        5   it's important for us to look at the science
        6   because -- as opposed to the simple whether or not
        7   you can correlate a serum level with a brain level of
        8   cholinesterase.
        9                 MR. GOSSELIN:  Yeah, I think I -- if
       10   this is consistent with what you're saying, that I'd
       11   see this workshop as not just a snapshot of the way
       12   we've been doing things.  
       13                 I think there has to be an explanation
       14   and rationale why we've done certain things the way
       15   we've done them to date so everyone can understand
       16   our policies.  
       17                 But I think we all know that science
       18   and understanding and knowledge is progressing and
       19   how that interfaces -- and as Dr. Seiber said, with
       20   EPA, it's sort of on the edge of that -- how that
       21   interfaces with regulatory agencies is, you know,
       22   another compelling issue.  How we absorb changes in
       23   science and knowledge into a regulatory program is
       24   very important.
       25                 So I see this is really trying to lay

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   out where a lot of the advances and new knowledge on
        2   these issues, sort of the -- where things may go for
        3   the future.
        4                 DR. FROINES:  We're currently doing
        5   work on two things:  We're looking at
        6   styrene-butadiene interactions, and we're looking at
        7   hexane-methyl ethyl ketone interactions, so we're
        8   doing a lot of PBK modeling and looking at those
        9   actual interactions between chemicals. 
       10                 And so I think one of the areas that I
       11   think is weak in your documents a little bit is
       12   discussion of toxicokinetics.  There are very few, if
       13   any, KM values and B maxes any place in the
       14   documents.  
       15                 And it seems to me that these issues
       16   about cross-species extrapolation require a good
       17   sense of toxicokinetics, and so that's one area that
       18   maybe not in the context of this workshop but we
       19   certainly need to think about it in the long term. 
       20                 Because it -- I think it's -- Craig and
       21   I were talking about it last night, and I think he
       22   would agree that the issues of clearance and just
       23   basic protein biochemistry is -- needs more
       24   attention.  And we need -- so we need to bring
       25   ourselves up to speed so that the panel is really

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   comfortable with those kinds of discussions.
        2                 DR. BYUS:  Yeah, my -- I mean, clearly
        3   we've identified the serum cholinesterase issue, but
        4   we did it after we looked at all the documents.  So
        5   my question is can we identify those issues until
        6   we -- do we have to wait until we see all the
        7   documents, or can we do it ahead of time.  
        8                 And it would be better if we could do
        9   it ahead of time and deal with those issues in a
       10   workshop rather than try and deal with them after. 
       11   But I think we need to rely on you -- I mean, "you"
       12   in the global sense -- to help us identify them on
       13   the front end before actually we sit and review all
       14   the documents.  Is that -- that's the way I look at
       15   it in terms of the health effectors, anyway; other
       16   than the ones we've already identified.
       17                 DR. SEIBER:  Yeah, I think that if we
       18   framed the question right to the outside experts what
       19   are the forefront leading edge issues.  And many of
       20   these experts go to the meetings in Washington with
       21   their EPA, SAP group, so they could bring that back. 
       22                 And I think it's a question of
       23   informing the process so we know what's going on, we
       24   know where science is going, we're regulatory so we
       25   can make the best decisions we can with what's on

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   that list of pesticides.  Unfortunately in one day we
        2   can't cover everything, so it's more a question of
        3   where you draw the line.
        4                 DR. FROINES:  I do think we're talking
        5   about a series of workshops.  It doesn't even have to
        6   include all the SRP members.  If they're not
        7   interested in something, they don't have to attend. 
        8   But there are enough scientific issues that if we're
        9   going to be spending most of our time -- George has
       10   sort of quit bringing things to us, and we can spend
       11   all our time on pesticides -- then we'll see about
       12   that.  But I think it could be fun, frankly.
       13                 DR. FUCALORO:  We have an agenda for
       14   the next workshop before us, and what you're
       15   discussing is a series of workshops which I agree is
       16   a good idea.  
       17                 I think you need some sort of task
       18   force to set up the agendas for those.  I think
       19   that's something that needs to be done next.  Don't
       20   you?
       21                 DR. FROINES:  Yeah.
       22                 So I think one of the things we should
       23   do is we have a group of three right now who we have
       24   identified.  We can see if when Dr. Paul Blanc and
       25   Peter Witschi are back if they want to participate.  

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1                 We might even ask people outside who we
        2   know who are doing work in the area to be a part of
        3   the team if there was somebody we can identify, and
        4   then the representatives from DPR and presumably
        5   somebody from OEHHA.  
        6                 And so it seems to me we would want to
        7   have an ongoing series of meetings who -- boy, we're
        8   bringing out everybody here in Riverside.  You bring
        9   the circus to town, everybody comes out.  
       10                 UNIDENTIFIED SPEAKER:  Absolutely.
       11                 DR. FROINES:  Dave Eastman's over
       12   there, and Paul Craner just came in.  Goodness.  We
       13   should have these meetings in these outlying places
       14   more.  We get to see our old friends.  
       15                 DR. FUCALORO:  Some of us don't
       16   consider Riverside an outside city.  I happen to, but
       17   some of us don't.  
       18                 DR. FROINES:  What the hell were we
       19   talking about?  
       20                 DR. FUCALORO:  We were talking about
       21   setting up -- I mean, I think I was setting a task
       22   force or a plan in order to establish agendas for
       23   future workshops and, therefore, cover the -- cover
       24   the areas we wish to cover, many of which were
       25   discussed here today.

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1                 DR. FROINES:  I think we should set out
        2   a plan, and I think we should set out a timetable,
        3   because this one has kind of drifted along for --
        4   since before -- since, what, summertime -- since 
        5   June -- since before June, and now we're into a new
        6   year.  
        7                 So I think what we do is we set up
        8   subject areas that we want to pursue and then we set
        9   up times and then we work and we stick with the
       10   times.
       11                 DR. SEIBER:  Well, the way I understand
       12   the conversation, we'll have a task force with SRP
       13   ideas on what could go into the workshop but will
       14   continue to work through the DPR staff.  
       15                 DR. FROINES:  Right.  
       16                 DR. SEIBER:  And I think that's kind of
       17   important.  I think DPR needs to, so to speak, learn
       18   how to do the workshops also because obviously we're
       19   not going to do the detail work.  And I'm happy that
       20   Paul has designated a person who can work with us
       21   who's had some experience in meeting organization
       22   already so --
       23                 DR. FROINES:  In fact, what happened
       24   with the workshop we did in March, we identified
       25   speakers and then Bill Lockett -- I think Bill called

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   everybody to get them to come.  I don't remember my
        2   calling people.  
        3                 Didn't you do the legwork on the
        4   speakers for the diesel workshop?  
        5                 MR. LOCKETT:  Yes.
        6                 DR. FROINES:  Yeah.  So I think
        7   absolutely.  We need that.  But we need the exchange
        8   to not be -- it needs to be an equal intellectual
        9   exchange as well as an equal work so it's not seen as
       10   staff and SRP at all.
       11                 DR. BYUS:  I think we should basically
       12   get together with your lead toxicologists on these
       13   documents and sit down for some small period of time
       14   and hopefully, you know, have them just say what are
       15   the issues and where are the gaps and do it for each
       16   one of the things that's going to come along and then
       17   who are the people we might get to bring in and talk
       18   about it.  Can we -- I mean, could that be done in a
       19   relatively short period of time?  Like a day?  
       20                 MR. GOSSELIN:  Yeah, for the ones
       21   coming up?
       22                 DR. BYUS:  For the ones coming up. 
       23                 MR. GOSSELIN:  It depends on how far
       24   along those documents are but, yeah, there's no
       25   problem doing that.  And I think, again, from what

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   issues -- I mean, for the ones that aren't done, we
        2   probably would have a good idea of the realm of what
        3   we've seen historically.  You know, we would probably
        4   cover most of the topics -- I mean, we might get
        5   surprised with a new, compelling issue but -- 
        6                 MR. BYUS:  Yeah, of course.
        7                 MR. GOSSELIN:  Right.  But I don't
        8   think that's a problem.
        9                 DR. BYUS:  That's the way I think we
       10   should do it, though.  I mean, does that seem
       11   reasonable?  
       12                 DR. FROINES:  I think we have to have a
       13   lot of back and forth between meetings.  But you
       14   know, I think what we should do is every time we have
       15   a meeting, since pesticide issues are going to be
       16   coming up fairly regularly, is we try to set aside a
       17   breakfast or after the meeting or the night before or
       18   something like that where we have actually had a --
       19   or try to have, if it can be fit into everybody's
       20   schedules, a working group meeting at the SRP
       21   meeting.
       22                 DR. BYUS:  That's a good -- great idea. 
       23                 DR. SEIBER:  But if we can keep the
       24   pressure on this one so we can -- you know, even
       25   February isn't that far off with the holidays, so I

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   think we're going to have to bring this first one to
        2   closure as soon as we can.
        3                 MR. GOSSELIN:  And I think even --
        4                 DR. FROINES:  The danger is that you
        5   have a meeting like this and everybody talks and is
        6   enthusiastic, and then you finish this meeting, and
        7   you say, "I'm glad that's over," and then you go on
        8   to your normal work, and things slip by the wayside. 
        9   So I think that's the message, what you see the
       10   danger is.
       11                 MR. GOSSELIN:  How soon would we be
       12   able to lock in a date in February?
       13                 DR. FROINES:  I think it's up to Bill
       14   to find when the panel's available.
       15                 MR. LOCKETT:  We'll need to poll the
       16   panel and figure out a date in February that will
       17   work.  
       18                 DR. FROINES:  There's a lot of snow on
       19   the mountains, so it's going to be difficult.  
       20                 DR. SEIBER:  We could have this meeting
       21   at Squaw Valley.  That's a possibility.
       22                 DR. FUCALORO:  Or Miami.
       23                 DR. FROINES:  Well, is there anything
       24   else that we need to -- I think that one thing we
       25   need to do is I think it would be good to have --

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   we've agreed that it would be good to have some
        2   industry representatives, not to lobby us but to talk
        3   about science that's going on; and clearly the other
        4   point is other members of the community who have an
        5   interest in pesticide issues we need to identify as
        6   well.
        7                 The Food Quality Protection Act seems
        8   to me to be really important because it's changing --
        9   may change everything.
       10                 DR. SEIBER:  Yeah, I think the -- just
       11   taking the aggregate exposure part of the Food
       12   Quality Protection Act, just that one part where you
       13   look at total exposures, as I mentioned, we didn't
       14   have to worry so much about that in the past.  And
       15   now that's right at the essence of what -- where the
       16   regulatory action is moving and rightfully so.  I
       17   mean, it only makes sense.  You've got to add all the
       18   exposures from all the media.  
       19                 But what it means for pesticides in air
       20   as toxic air contaminants is you don't just do that
       21   in a vacuum.  You've got to link it up with food and
       22   water and the other exposure routes.  
       23                 And where we used to be able to talk
       24   about outdoor versus indoor and we kind of said,
       25   well, we're not so worried about indoor air because

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   that's not the mandate that we live under, well, you
        2   can't do that anymore.  I mean, you never could in
        3   the past, but we kind of artificially did.  But you
        4   just can't do that.
        5                 DR. FROINES:  Well, let's move on. 
        6   There was something I wanted to say but -- oh,
        7   George, who is a point person for us to talk with
        8   about this workshop issue?  
        9                 DR. ALEXEEFF:  George Alexeeff with
       10   OEHHA.  
       11                 Well, you could start with me, and I
       12   could point to you depending on the specific
       13   individual.  If we're talking about organophosphate
       14   mechanism action, we have the individual here, one of
       15   the staff people here.  If we're talking a little
       16   more global pesticide questions, it might be a
       17   different individual.  
       18                 But we would get one of the members of
       19   our pesticide section that would be knowledgeable on
       20   the specific experts on the issues depending upon how
       21   specific the workshop was set up.
       22                 So -- so if there's -- you could start
       23   with me, and I could just point to you depending upon
       24   the specificity or the area of the pesticide
       25   toxicology.

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1                 DR. FROINES:  You know, one thing,
        2   looking in the back and seeing my Ph.D. student
        3   Lupita Chapa here, is one of the issues that we're
        4   dealing with in thorium in Mexico is we don't deal
        5   with -- we don't have the luxury of studying DEF and
        6   then studying methyl parathion because, you know,
        7   down there everybody's exposed to eight or ten
        8   pesticides.  
        9                 So we have to deal with the question of
       10   how do you deal with everybody from antibiotics on
       11   the one hand to methamidophos to residual DDT in the
       12   soil.  So we have a very complicated exposure
       13   pattern.  And actually, that undoubtedly occurs here
       14   too.  
       15                 And so one of the questions becomes at
       16   some point we have to bite the bullet and take on the
       17   multiple exposure issue.  I don't think we can leave
       18   it aside.  It is what happens.  And health effects
       19   derive not from single chemicals.  They derive from
       20   combinations of chemicals.  
       21                 I just reviewed a paper for Witschi
       22   on -- what the hell was it? -- diazanon and methyl
       23   parathion.  So at some point I think it's important
       24   that we do that.  
       25                 And so at some point it would be

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   interesting for us to learn from you something about
        2   the mixtures of exposures to pesticides that actually
        3   occur in your experience and something about the
        4   temporal characteristics of that as well.
        5                 MR. GOSSELIN:  Yeah.  I think even the
        6   work and struggle that EPA is going through with FQPA
        7   and actually some of the panels that put together to
        8   try to investigate this might -- might be helpful. 
        9                 Because EPA is trying to formulate some
       10   policies on that, and it's -- even among
       11   organophosphates it's a pretty complicated task on
       12   how to go about doing that.  And that might be a
       13   topic for future discussion, for a future workshop.
       14                 DR. FROINES:  I want to say one thing. 
       15   It seems to me that this panel gets $100 every time
       16   it meets, and it's made up of all very busy people. 
       17   And Bill Lockett would like us to work full time for
       18   these issues, and there's a constant battle with
       19   that.  
       20                 And what I'm saying is it may be that
       21   because I have some interest in pesticides that I'm
       22   more willing to put time in outside of the normal
       23   role to work on some of these things, and Seiber
       24   probably has the same commitment because of his
       25   interests, and maybe Craig does.  But Gary has a very

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   different agenda, and I -- Tony, you know, may have
        2   his own agenda, clearly has his own agenda.
        3                 DR. FUCALORO:  Several of them.
        4                 DR. FROINES:  Several of them.  And so
        5   it may be that we will see different levels of
        6   participation, and we should be willing to accept
        7   that.  
        8                 Because when we have workshops, we're
        9   not necessarily always dealing with a quorum
       10   situation.  So I think we do have to acknowledge that
       11   some people on the panel may or may not be as active
       12   in participation as others and accept that, although
       13   when we actually make regulatory decisions we're
       14   going to have to have everybody knowledgeable.
       15                 But if in fact Craig learns more about
       16   plasma cholinesterase and there's communication with
       17   Gary or -- I'm not trying to exclude you -- I'm
       18   simply trying to be realistic about people's time --
       19   that it will be a learning process and it will have
       20   broad --
       21                 DR. FRIEDMAN:  I think, you know,
       22   people like me, I probably will benefit more from
       23   such a workshop because there's a lot I would learn
       24   from that.  
       25                 I thought you were going to say that

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   you should get $200.
        2                 DR. FROINES:  Well, I think we should
        3   do that because I'm on the carcinogen identification
        4   committee, and it's more lucrative to be on that
        5   committee.  So that there needs to be an issue of
        6   equity.  But now that we've had an election, we'll
        7   get -- those things will get straightened out, I'm
        8   sure.
        9                 DR. SEIBER:  Let me just try a
       10   suggestion now since we've had some good ideas here
       11   in discussion.  And I don't know how -- what level of
       12   specificity you want to get into it now, but it seems
       13   since we're all focused in now on the workshop
       14   agenda, what if we added in under environment
       15   monitoring and fate a discussion of aggregate and
       16   cumulative exposure in the latest thinking.  I know
       17   that in itself is huge.  But just to bring the key
       18   issues out.
       19                 DR. BYUS:  I think that would be
       20   wonderful.  
       21                 DR. SEIBER:  And then under the
       22   endpoints we talked -- John brought up the
       23   neurological effects of not just -- well, I guess
       24   organophosphates but also other pesticides.  
       25                 And when I read this draft agenda over,

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   I thought we ought to be able to cover in three hours
        2   more than just cholinesterase.  That seemed like it
        3   was too heavily loaded on cholinesterase and maybe if
        4   we had another topic in there.
        5                 DR. BYUS:  Maybe like the mechanism of
        6   the delay in neurotoxicity I think is something that
        7   is not particularly clear.
        8                 DR. FROINES:  That's not so simple to
        9   cover in three hours.  It's a lot.
       10                 DR. BYUS:  It is.  Well, as a
       11   possibility.  
       12                 DR. FROINES:  There are different
       13   levels of it too.  
       14                 DR. BYUS:  Right.  
       15                 DR. FROINES:  Because you have the
       16   issue of what it is and all of that and the
       17   mechanistic detail.  And then you have using hens for
       18   testing and then what do you do about the
       19   toxicokinetics of hens.  So I mean, you can bite off
       20   a lot of pieces on that subject.  So we have got to
       21   be careful that we don't, you know, get too spread.  
       22                 So we're done on this one, aren't we? 
       23   Probably more than done.
       24                 DR. SEIBER:  What's going to happen
       25   next?  Are we going to get this group together by

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   telephone or something like that and maybe with OEHHA
        2   and DPR people also?  
        3                 DR. FROINES:  I'd propose that probably
        4   it makes most sense, given that he's in Riverside,
        5   I'm in L.A., you're in Sacramento, and he's somewhere
        6   between Nevada and Davis, that we have a conference
        7   call next week.  And we'll work it out when that will
        8   be.  And we start -- and I would even argue that we
        9   set up a series of regular conference calls so that
       10   we -- so we don't let the thing drop.  
       11                 That's what I think the biggest --
       12   putting on workshops like diesel was very easy
       13   because we knew all the players and we said, well,
       14   it's going to be boom, boom, boom boom, boom, and
       15   that's it.  And we just called them, and they came. 
       16   Here we don't necessarily know all the players, and I
       17   don't think any of us do.  We all know pieces of it.  
       18                 So I think we need to have a regular
       19   process of -- to keep this stuff going.  Otherwise
       20   it's going to have a tendency to drift the way it's
       21   been drifting.  Even though Jim's been trying to push
       22   it along and everybody's tried to deal with it, it's
       23   still drifting.
       24                 MR. GOSSELIN:  And I think because we
       25   haven't done this workshop before and a lot of these

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   topics may be very broad and we are looking at a
        2   series that to get something going that we know is
        3   achievable even if it may seem that the topics aren't
        4   going to cover three hours, I -- my own personal
        5   perspective, I'd like to get a nice meeting we have
        6   that's solid to build from rather than something that
        7   we overload, have it be muddled, and everyone feeling
        8   frustrated that we haven't accomplished much.
        9                 DR. FROINES:  Based upon what we've
       10   said today, you know what might be very useful for
       11   you to do is after this meeting is to go back and
       12   have a meeting in Sacramento and have your -- the
       13   people who are the most technical people in DPR, for
       14   them to sit down and come up with a list of what they
       15   consider some of the most important and interesting
       16   and topical scientific issues or scientific/policy
       17   but by and large scientific issues, and then we can
       18   see the benefit of that input.  
       19                 And I don't think people need to
       20   necessarily get their heads locked into a regulatory
       21   framework.  Looking at what are underlying issues
       22   that help us define dose response from mechanism and
       23   what are some of the questions associated with that
       24   would be very useful to have as a starting point for
       25   trying to come out with we may end up picking two or

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   three things and say let's just go with that.  But
        2   having it be an intellectual exercise and not just
        3   show and tell is what we're really after.
        4                 So we'll set up the meeting.  Bill can
        5   set up the meeting for sometime next week.  
        6                 DR. ALEXEEFF:  George Alexeeff.  
        7                 If I could just make a side comment
        8   since we seem to be starting with the last item on
        9   the agenda, and that has to do with the next coming
       10   meeting in December. 
       11                 One of the items on the proposed agenda
       12   is our acute methodology for risk assessment,
       13   methodology for doing acute risk assessment, and so
       14   that will work out very well with the issues being
       15   discussed with DPR because we will be trying to
       16   present at least, you know, our sort of framework on
       17   how we evaluate acute non-cancer endpoints.  
       18                 So I think this year -- it looks like
       19   the agenda for this year will be a lot of evaluation
       20   of non-cancer endpoints, both the acute and the
       21   chronic, which would be, I think, rather
       22   scientifically interesting and challenging for the
       23   committees.
       24                 DR. FROINES:  George, how long do you
       25   think that's going to take?  

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1                 DR. ALEXEEFF:  Well, the leads on the
        2   document are Dr. Seiber and Glantz.  And they had
        3   asked us to -- since it's a different approach, we're
        4   concerned about -- mostly about the methodology,
        5   although we have 50 substances where we've
        6   implemented the methodology.  
        7                 They wanted the presentation to be
        8   loaded with examples of the methods.  So kind of go
        9   through the method, like here's this method we're
       10   discussing, and to give an example of how it actually
       11   works and what the issues and uncertainties and
       12   problems with that method are.  Because every method
       13   we come up with has its shortcomings.  It's not a
       14   perfect, ideal situation.  But we work with the data
       15   that we have.  
       16                 So it's going to be kind of a lot of
       17   examples and explanations of things that the way we
       18   use the data and the way we give those examples.  So
       19   that itself will take, you know, at least an hour or
       20   two just discussing the issues and the methods.  
       21                 And then there obviously will be
       22   questions about the specific chemicals and how maybe
       23   those methods were applied to those chemicals.  So
       24   like, for example, one issue that comes up and it
       25   comes up also for the pesticide documents is using

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   the developmental or reproductive study and trying to
        2   determine whether it has acute application or
        3   acute -- you know, for acute exposure.  
        4                 And that's an important issue, and you
        5   can see how we've tried to do that.  That itself can
        6   go on for a reasonable length of discussion.  So but
        7   there's going to be a number of those, probably ten
        8   issues like that.
        9                 DR. FROINES:  You're like my wife. 
       10                 DR. ALEXEEFF:  I'm sorry -- or thank
       11   you.
       12                 DR. FROINES:  You're like my wife.  I
       13   ask her a question, and then she answers it whichever
       14   way she chooses to, which has nothing to do with the
       15   question I asked most of the time.  She has her own
       16   agenda, and she pursues her agenda.
       17                 DR. FUCALORO:  That's the definition of
       18   a politician.  Maybe a wife, too, but certainly a
       19   politician.  
       20                 DR. FROINES:  So George, help me out
       21   here.  Give me a time.  
       22                 DR. ALEXEEFF:  My sense of what will
       23   happen is it will take at least a half a day.  You
       24   know, we're talking like three hours.  And I have a
       25   feeling it will roll over to another meeting, the

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   subsequent meeting.
        2                 DR. FROINES:  So we're at a half a day. 
        3   The reason I'm -- because I think we can finalize our
        4   agenda for the next meeting right now.  That's half a
        5   day.  We'll finish methyl parathion, and we'll have
        6   an update on the workshop.  And I think we just did
        7   the -- unless somebody has anything else to say, I
        8   think we just did the agenda.
        9                 MR. GOSSELIN:  Yeah.  We also are going
       10   to present molinate.  
       11                 DR. FROINES:  After George said all
       12   that?
       13                 MR. GOSSELIN:  I said --
       14                 DR. ALEXEEFF:  Why do you think I said
       15   it first?  
       16                 MR. GOSSELIN:  We're prepared and
       17   willing.  But I know that will take a couple hours.
       18                 DR. SEIBER:  Yeah, I know a little bit
       19   about the molinate issues, and that's an important
       20   one.  We want to make sure we save plenty of time. 
       21   But on the other hand what George mentioned, as we
       22   get away from this hypnotism on cancer as the only
       23   endpoint out there, I think this is just really
       24   important stuff.  And so they're both important. 
       25   We've got to spend time on them.  

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1                 DR. FROINES:  Well, Paul, we have to do
        2   methyl parathion.  We have to have a -- what we
        3   should say is a five- to ten-minute update on the
        4   workshop so we don't bog down on it.  
        5                 We've got George who wants half a day,
        6   but it sounds like it will take a week if we gave it
        7   to him.  And then we have molinate.  And that's too
        8   much for one day.  
        9                 (Off the record.)
       10                 MR. FROINES:  Maybe what we can do with
       11   molinate -- first, is Paul's not here, but does Paul
       12   have an early draft?  Do you have an early draft of
       13   the document?  
       14                 MR. GOSSELIN:  Yeah.  Actually, we have
       15   had at least one conference call and some written
       16   comments on some issues.  So what -- I think what you
       17   were leading to is if we'll continue to work with the
       18   leads on molinate and maybe at that meeting not have
       19   a full presentation but a synopsis presentation of
       20   the overheads.  
       21                 And actually, we'll have completed the
       22   public comment period, so we could probably provide
       23   some of the background preliminary information and
       24   work out a lot of the issues with the leads prior to
       25   that meeting.

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1                 MR. FROINES:  What we did with diesel
        2   last October is we weren't prepared to discuss it and
        3   there were still changes being made by George and his
        4   staff.  
        5                 So what George did is they came and we
        6   spent part of the day -- basically it was an
        7   informational presentation.  And then at two
        8   subsequent meetings we took up diesel in detail.  
        9                 I think that -- unless anybody
       10   disagrees, that seems to me to have been a useful way
       11   of doing it.  And so if what you did was made a
       12   preliminary presentation, we could get feedback --
       13   the panel could get feedback from the leads to hear
       14   what their concerns are, and then we can take it up
       15   at the next meeting in some detail.
       16                 MR. GOSSELIN:  Right. 
       17                 MR. FROINES:  Does that make sense? 
       18                 DR. ALEXEEFF:  If I may add, that may
       19   be what also happens with the acute document as well. 
       20   I mean, I think it will go over probably to the
       21   following, subsequent meeting.  And that's just my
       22   thought.  
       23                 Because there's potentially 50
       24   substances that people might want to -- after we've
       25   discussed the technical issues -- may want to look at

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   again.  
        2                 We can just -- we're open to any sort
        3   of format.  But I think for that sort of thing we're
        4   approaching a new -- considering new methodology.  I
        5   think two meetings is very likely also for that
        6   document as well.
        7                 DR. FROINES:  Well, the one thing --
        8   Bill, the one thing that's becoming clear in this
        9   meeting and I think has been becoming clear for the
       10   last year, in fact, is that we are -- we went -- for
       11   those in the audience who don't know, we went for,
       12   what, 18 months without a meeting at one point. 
       13   There were some political problems going on that had
       14   to be resolved.  
       15                 But now it looks like we're going to be
       16   meeting monthly on an -- on an indefinite basis. 
       17   That's the feeling I'm getting.  And with the
       18   workshops you may actually have more.  So we're
       19   talking about quite a heavy workload.  Everybody
       20   needs to be aware of that, I think.  
       21                 DR. ALEXEEFF:  Well, just in terms of
       22   the OEHHA documents, what we see for the year are
       23   essentially three documents.  But each document is
       24   very complex and has a lot of issues.  But that's
       25   what we're expecting to bring to the panel, just

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   those three.
        2                 DR. FROINES:  Are they expecting to
        3   bring any chemicals to the panel?  
        4                 DR. ALEXEEFF:  Those three documents
        5   I'm referring to are methodology documents with -- I
        6   mean, it will cover a total of over 170 chemicals
        7   between the documents.  
        8                 But it's mostly the methodology used
        9   and then the application of that methodology as
       10   opposed to an in-depth discussion of a single
       11   chemical or a couple chemicals.  So it will be a
       12   little bit different.
       13                 DR. FROINES:  Well, we're not going to
       14   get an MTBE or diesel or some more traditional
       15   compound?  
       16                 DR. ALEXEEFF:  MTBE is probably the
       17   other substance that could come before the panel from
       18   us.  It will probably be very similar to the other
       19   MTBE documents that our department is developing.  We
       20   have already developed three documents in MTBE.  
       21                 And so it's very likely after the CIC
       22   meeting in December and the reproductive meeting in
       23   December -- those are our departmental meetings on --
       24   with science panels -- that we may then be developing
       25   an air document on MTBE.  

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1                 So that could come.  But that will take
        2   some time and probably won't be available -- we're
        3   talking until later in the year, next year, calendar
        4   year.
        5                 DR. SEIBER:  Well, that raises the
        6   whole question of we saw a prioritization list -- oh,
        7   I don't know, maybe in the springtime -- that had
        8   styrene and MTBE and a lot of different things on it. 
        9   I think it would be kind of nice to have an update on
       10   it.  Because I had the impression that maybe styrene
       11   would be coming along this year.  
       12                 DR. ALEXEEFF:  We're also starting to
       13   work on styrene, but I think that one's going to be a
       14   little long and difficult document to prepare, so I
       15   don't think it will be ready this year.  It might be.
       16                 DR. FROINES:  But the panel is -- this
       17   discussion is such that I think it's pretty clear
       18   that we're going to be working on a relatively
       19   ongoing basis for the next period of time.  
       20                 DR. ALEXEEFF:  I mean, the other
       21   substance that has come up and in part because of
       22   DPR's work has to do with crystalline silica.  That's
       23   another substance that will be -- that ARB has asked
       24   us or notified us that they will be requesting us to
       25   prepare a document on that as well.  

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1                 And then the other one was PAHs and
        2   nitro PAH documents and looking at how to consider
        3   the more multiple issues involved with genotoxicity
        4   and such.  So those are the -- that's pretty much the
        5   summary of the documents that we see in the horizon
        6   over the next year that the staff will be working on.
        7                 DR. FROINES:  Well, I can suggest a
        8   couple more I think that you should put in your --
        9   the back of your head.  One is aldehydes as a generic
       10   group because they're very reactive and they're
       11   important.  
       12                 And for example, you know that HEI had
       13   an RFA out last year about aldehydes so that they're
       14   certainly -- at the national level they're concerned
       15   about that as a class of compounds.  
       16                 And then related to the PAH aldehyde
       17   issue is those compounds that produce oxidative
       18   stress.  Reactive oxygen species -- quinones, for
       19   example -- are the ones that we're interested in. 
       20                 But the whole issue of electron
       21   transfer reaction, electron stress, oxidative stress,
       22   all of that seems to me -- and all of that, again, is
       23   related to mobile sources to a large degree.  
       24                 And it seems to me that we have -- if
       25   you sort of say what are the most important air toxic

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   compounds, it's not just looking at your isolated
        2   individual carcinogen spewing out of some factory.  
        3                 I mean, I think that the mobile source
        4   issue around reactive oxygen compounds is really
        5   important and certainly aldehydes, it is important,
        6   especially with the oxygenates where you are
        7   generating formaldehyde and acid aldehyde and then
        8   peroxy acetyl nitrate and the others.
        9                 And so it seems to me that we need to
       10   identify those compounds not just -- you know, we got
       11   a list where we had this compound, a sole tone
       12   compound, that's been banned for 20 years on
       13   somebody's list.  
       14                 And so we really ought to say what are
       15   the really most important compounds and let's go
       16   ahead and talk to the panel about that and you can go
       17   to work on it.  
       18                 DR. ALEXEEFF:  Uh-huh.
       19                 DR. SEIBER:  But one thing -- this
       20   document that we're going to take up, this is really
       21   loaded with information.  We -- this is a here and
       22   now.  It's done.  It's ready to go.  This is the
       23   acute reference exposure levels for airborne
       24   toxicants.  I think it's extremely important.  
       25                 So all things are coming along, but

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   this one here deserves a lot of attention because
        2   there's some good work here.  And I think it's kind
        3   of unique to California.  So this is what we're
        4   looking for.
        5                 DR. FROINES:  I'd like to see -- you
        6   know, if you take PAN, for example, the data on PAN
        7   is very limited.  It's genotoxic.  There's evidence
        8   of carcinogenicity.  There's evidence of lung
        9   effects.  
       10                 We know that if you use ethanol, you
       11   start to get a lot of PAN because you have a lot of
       12   acid aldehyde in an environment like L.A. where you
       13   have a lot of nitrogen oxides and so on and so forth.  
       14                 The data on PAN is really deficient
       15   from a regulatory standpoint.  You would want more
       16   before you labeled it as a toxic air contaminant.  So
       17   one of the things, it seems to me, George, is to be
       18   thinking about as you look at reactive oxygen
       19   compounds is to also develop a list that says,
       20   "Research needs to be done in these areas, and here
       21   is the kinds of research we think needs to be done,"
       22   and DPR the same way to create out of a regulatory
       23   process, to create a research agenda at the same time
       24   to fill gaps and that -- so that the regulatory
       25   process doesn't always have to be quite as -- so

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   like, you know, like a civil engineer, a linear
        2   process.  
        3                 DR. ALEXEEFF:  And if I may plug the
        4   document again that Dr. Seiber was raising, there's
        5   actually one thing different with this document.  We
        6   do have a research need section in there.  
        7                 So we can look at that, how we can work
        8   that kind of section, so that we -- because it just
        9   seemed to us we knew where all the data gaps are.  It
       10   was important just to outline them there in general. 
       11   The outline is there as to where a lot of research as
       12   to go for the acute toxicity arena makes sense.
       13                 DR. FROINES:  I think one of the things
       14   I'd like to see coming out of the DPR interaction is
       15   more a sense in the academic community of what our
       16   research -- some of the research issues that you
       17   think are particularly important and would be helpful
       18   as we move forward to actually build this linkage
       19   between the government regulatory agencies and the
       20   academics in California who are doing research in
       21   these areas.  That -- those linkages haven't been
       22   extended enough and I think could be.
       23                 So should we move on?  Yes.  It's good
       24   to have that discussion.  We won't have it again.  
       25                 MR. FRIEDMAN:  It seems like it took

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   quite a long time.  
        2                 DR. FROINES:  Let's move on to DEF.
        3                 MR. GOSSELIN:  Thank you.
        4                 Since the last meeting, we went through
        5   and we did post DEF out for another round of public
        7                 One thing you should also take a look
        8   at is we started a process of actually posting our
        9   documents even for comment period on our Internet
       10   home page.  And we're looking to enhance that and
       11   actually have it cross-linked with ARB's SRP page
       12   which I think in the future will be real helpful to
       13   people coming in looking for the agenda schedule and
       14   documents.  
       15                 So we did go out.  We had opened up the
       16   comment period, sent a notice out to the interested
       17   party list for DEF, and went through that.  I don't
       18   believe we got any comments back during that process. 
       19                 But the one thing that we did go
       20   through is we did send to you a summary list of the
       21   changes that were brought up at the last meeting to
       22   the document, and they're bulleted as sort of a frame
       23   of reference, and we faxed out to you the actual
       24   change of the text to the original document that
       25   would make it easier to see where we inserted it. 

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   And today we have the sort of revised document that
        2   incorporates those changes.
        3                 DR. FROINES:  Is that this document
        4   (indicating)?  
        5                 MR. GOSSELIN:  What's the date on that?
        6                 DR. FROINES:  November '98.
        7                 MR. GOSSELIN:  That should be it,
        8   right.  
        9                 So that document has the changes that
       10   were faxed out to you a week or two ago.  So I don't
       11   know if you wanted me to go through each one of those
       12   changes or if there were questions on that.
       13                 The other thing is we've been working
       14   with ARB and the panel on the draft findings which
       15   you have the latest copy of.  Those reflect comments
       16   that were submitted in over the past couple weeks.
       17                 DR. FRIEDMAN:  I have a question about
       18   the findings.  Is this an appropriate time?  
       19                 MR. GOSSELIN:  Uh-huh.  
       20                 DR. FRIEDMAN:  I'm not clear on the
       21   logic and the reasoning that lead to this being
       22   labeled as a "toxic air contaminant."  You know, I'm
       23   convinced that it's a poison.  I wouldn't want to eat
       24   it or have anyone else eat it or breathe it, but I'm
       25   just wondering if we're not stretching a bit to meet

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   this definition.                
        2                 The margin of exposure, you know, for
        3   the acute effects was very high so that it seems like
        4   it wasn't labeled as a toxic air contaminant based on
        5   that but rather on the carcinogenic effect or the
        6   carcinogenic risk.  
        7                 And in order to be labeled as a toxic
        8   air contaminant, it needs to be -- cause one cancer
        9   case out of ten million people, as I understand it,
       10   one-tenth of the -- of the significant exposure.
       11                 So -- and in order to meet that
       12   criteria, it seemed like you had to say that the
       13   exposure lasted a lifetime.  And no -- I don't
       14   believe that this -- anyone has ever been exposed to
       15   this substance for a full lifetime.  
       16                 So I'm just wondering -- I'd like to
       17   understand better how one comes up with the
       18   conclusion that this is a "toxic air contaminant" by
       19   the definition that's given in here.
       20                 DR. FROINES:  But there's a -- can I
       21   interrupt, Paul, before you get started?  Because I
       22   think there's a prior issue that we would -- it would
       23   be nice to have Stan here since he'll be very -- I
       24   was going to say articulate but I think outspoken. 
       25   Outspoken may be the more accurate way of describing

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   it.
        2                 We have to make a decision separate
        3   from Paul.  In the past we have declared compounds
        4   as -- we have recommended that compounds be declared
        5   toxic air contaminants based on no quantitative
        6   estimate of exposure or risk.  
        7                 We have made -- risk assessments have
        8   been made in documents, but there hasn't been a
        9   bright line for us.  We've never had a bright line. 
       10   With a compound that's carcinogenic we've said it's a
       11   toxic air contaminant irrespective of what the bright
       12   line of 10 to the minus 5, or 10 to the minus 6, or
       13   10 to the minus 7.  
       14                 So the actual use of the risk
       15   assessment for purposes of defining a substance as a
       16   toxic air contaminant has never occurred for this
       17   panel.
       18                 We have made the decision based on the
       19   general -- the very general definition that we all
       20   are aware of.  And so the -- we have to decide
       21   whether we want to recommend as a panel that
       22   something be declared a toxic air contaminant or
       23   whether we want to accept the language that is
       24   basically in this report.  
       25                 It says, "We agree with the science and

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   recommend that the director initiate regulatory steps
        2   to list DEF as a toxic air contaminant," and that's
        3   different.  They are different ways of doing it. 
        4                 DR. FRIEDMAN:  Well, it's obvious this
        5   is a toxic substance, so why did we go through -- I
        6   mean, is it just a no-brainer?  I mean, why did we go
        7   through all these calculations and measurements and
        8   so on if it's -- you know, nobody denies that this is
        9   a toxic substance and, yes, some of it gets into the
       10   air.  So why did we go through all of this?  
       11                 DR. FROINES:  Well, because this panel
       12   has historically disagreed with DPR on this issue. 
       13   It's been a fundamental disagreement since the early
       14   '80s.  And we've argued -- and now it's not quite as
       15   contentious an argument, but there are -- but we have
       16   disagreed.
       17                 And there is a court case under the
       18   Toxic Substances Control Act where a judge in
       19   Washington on an EPA where industry argued to take
       20   into account exposure.  
       21                 The judge overruled that and said that
       22   a rattlesnake in a bottle is toxic whether it's in
       23   the bottle or not and so that whether or not the
       24   rattlesnake was out of the bottle doesn't define
       25   whether the substance is toxic or not.

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1                 So that's the disagreement we've had
        2   historically with DPR, that DPR uses their estimated
        3   exposures as a way of calculating their MOEs and then
        4   the MOE is 7,000 times above some number.  
        5                 And so we're all safe as long as that
        6   estimate of exposure is correct or that it doesn't
        7   get used more or that something doesn't happen that
        8   makes that estimate of exposure turn out to be not
        9   correct.  
       10                 And some of our -- some of the
       11   disagreements has to do with concerns about that
       12   exposure.  So the issue for us is in essence to do it
       13   our traditional way or to basically pursue it the way
       14   DPR would prefer to do it.
       15                 DR. FRIEDMAN:  Well, is what I see in
       16   this document our traditional way or not?  
       17                 DR. FROINES:  Not really.  
       18                 DR. FRIEDMAN:  Because this document is
       19   supposed to be coming from us, not from them.
       20                 DR. FROINES:  So it's -- yeah.
       21                 DR. FRIEDMAN:  How would you word,
       22   then -- speaking for the panel, how would you word
       23   the conclusion that this should be labeled as a
       24   "toxic air contaminant"?  
       25                 DR. FROINES:  Well, you can take out

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   any one of our older documents and read it.  I think
        2   at the end of our older documents we say the SRP
        3   finds the evidence is compelling and recommends that
        4   diesel will be declared a toxic air contaminant.
        5                 DR. FRIEDMAN:  Not because it can cause
        6   cancer in a certain number of people.  If it can 
        7   cause cancer in 100 million people, it's still a
        8   toxic air contaminant?  In one in 100 million?  
        9                 DR. FROINES:  Right.  
       10                 And that's been the basis of the
       11   disagreement.  And that's -- and there are different
       12   levels of -- this document -- I don't see any -- oh,
       13   yeah, they are.  They've put the MOEs in the document
       14   as our findings.  It's up to this panel.
       15                 DR. SEIBER:  I don't know.  I have a
       16   problem with this discussion.  One reason we asked
       17   DPR to assemble this table, which is in the executive
       18   summary, which has got all the chemicals that we've
       19   ever declared as toxic air contaminants with DEF in
       20   its appropriate ranking, was to kind of help put
       21   things in perspective.  And it's pretty clear it's
       22   kind of in the middle on a potency basis.  
       23                 The difference is -- and this is what
       24   we're talking about now -- is the exposure.  I don't
       25   have another table like this with the -- to compare

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   the exposures.  
        2                 My guess is the DEF exposure will be
        3   lower than let's say for ethylene -- inorganic lead
        4   or ethylene dichloride -- or benzene.  I don't know
        5   that for a fact because I didn't go back.  
        6                 And that means a lot to me when I'm
        7   trying to consider whether this is a problem or not. 
        8   The exposure is almost off the chart.  I mean, there
        9   is exposure, but it is very low.  Then it shouldn't
       10   be -- you know, on a relative basis it's not the kind
       11   of threat that some of these other chemicals are.  So
       12   is that our business or not?  
       13                 And I'm not sure I understand this
       14   discussion about exposure levels.  I think they are
       15   very important.  And of course, part of our document
       16   is on exposure levels, so how can we -- how do we
       17   deal with that on the final conclusion?  
       18                 DR. FUCALORO:  You know, I'd like to
       19   make an observation, someone who's not been on the
       20   panel for very long.  I've read a while back the law
       21   which controls the designation of TACs, and it
       22   occurred to me that the hurdle is very low, that they
       23   use the word "may pose a threat" -- I'm not quoting
       24   exactly -- it's just my recollection -- to human
       25   health.

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1                 It seems to me almost any chemical you
        2   choose could fit that definition.  I mean, it seems
        3   to me -- I'm not sure we've ever turned down -- I am
        4   not sure.  Did you ever turn down a chemical that
        5   came before us as a TAC to be designated?
        6                 So I think the key to it has to be the
        7   priority list.  And that priority list -- and as I
        8   recall, the criteria used in -- I think it's OEHHA
        9   includes not only toxicity but also exposure.  And so
       10   you have a combination of those two.  
       11                 Whether or not it makes sense, I have
       12   no basis for judging that because I don't have
       13   experience in the area.  But I assume people in OEHHA
       14   have an enormous amount of experience.  And to work
       15   out a balance between toxicity and exposure to decide
       16   which one comes before us.
       17                 Now, what is the value of doing that if
       18   in fact we know the endpoint; that is to say that
       19   they probably will be designated a TAC.  It seems to
       20   me that the reason we would do that is to get the
       21   best scientific information available to show how
       22   dangerous that chemical is, that substance is,
       23   exposure and inherent toxicity, so that mitigation
       24   can proceed from there.
       25                 So I think that's what we're doing

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   here.  The fact that -- I too was struck by the fact
        2   that the conclusion in supposedly our document has us
        3   recommending designation as a TAC, and when I look at
        4   the data, I say jeez, I mean, this doesn't seem to be
        5   a big problem.  I mean, a combination of toxicity and
        6   exposure.  But I don't know.  
        7                 It seems the law -- and Bill could help
        8   us on this -- the law almost forces us to designate
        9   these things TACs given the low hurdles in that
       10   regard.
       11                 MR. LOCKETT:  It seems to me that what
       12   the panel is about is deciding whether the report
       13   represents the best current science.  It also seems
       14   to me that the panel is responsible for its own
       15   findings as to what it wants to state about that
       16   science.
       17                 I think historically the 1807 process
       18   as practiced by the resources board is that the board
       19   looked at the matter in two phases:  risk assessment
       20   and risk management.  And to progress to the risk
       21   management phase a risk assessment report needed to
       22   be created, developed, approved by the SRP --
       23                 DR. FUCALORO:  Mitigation.  
       24                 MR. LOCKETT:  -- go to the board, and
       25   the board would say, yes, we agree this is the

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   current science, yes, we declare under law this is a
        2   toxic air contaminant, and that began then the risk
        3   management phase.
        4                 DR. FUCALORO:  Right.  And risk
        5   management would be mitigation in that regard.  I
        6   used the word "mitigation," but I know there's
        7   assessment and management.
        8                 DR. FROINES:  No, but I think the point
        9   he's trying to make -- the point he's making is that
       10   the determination of whether something represents a
       11   problem is a risk management issue.
       12                 MR. LOCKETT:  Yes.  And there have been
       13   cases where the risk assessment has been completed
       14   but then because of the actions that have already
       15   taken place, no formal risk management process was
       16   undertaken.
       17                 DR. FUCALORO:  I understand that.  But
       18   it still might be designated as a TAC.
       19                 MR. LOCKETT:  Oh, yes.  
       20                 DR. FUCALORO:  Exactly my point.  But
       21   the question I think Dr. Friedman was -- or the issue
       22   Dr. Friedman was bringing up was the actual
       23   designation or the recommendation that something be
       24   designated a TAC, in this case DEF.  And I guess my
       25   observation is that almost anything brought before us

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   would fit the definition of a TAC.
        2                 MR. LOCKETT:  Correct.  In part because
        3   of prioritization.
        4                 DR. FUCALORO:  But it's important for
        5   us to carry out this process so that we can get the
        6   best science available as to what -- to do the best
        7   risk assessment.  I use different words, but that's
        8   the -- that's the same term.  So that people
        9   following us based upon this designation can do the
       10   best risk management mitigation.  
       11                 MR. LOCKETT:  Correct.  
       12                 DR. FUCALORO:  I think I understand it
       13   in those terms.  
       14                 So even though we look at a particular
       15   substance like DEF and say, "Well, the cancer potency
       16   is very low," but those numbers have to be provided
       17   or have to be -- we have to validate those numbers to
       18   some extent by saying good science was used to come
       19   up with those numbers to give guidance to regulatory
       20   agencies on how they might mitigate; in other words,
       21   how they might manage the risk.  Is that --
       22                 DR. FRIEDMAN:  Yes.  But I'd like to
       23   suggest that the placement of this substance on that
       24   table is not appropriate.  When we've looked at
       25   others, it seems reasonable to assume a lifetime

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   exposure, a many-year exposure.  
        2                 DR. FUCALORO:  That's a good point. 
        3                 DR. FRIEDMAN:  But here we're assuming
        4   a lifetime exposure to calculate this risk when there
        5   is no lifetime exposure.  So I would think it would
        6   fall much lower in this table than it's being put.
        7                 DR. FUCALORO:  That's a good point.
        8                 DR. FROINES:  But I think that there's
        9   a little apples and oranges going on here.  There's
       10   one element which is the unit risk value for DEF
       11   irrespective of whether lifetime exposure is above
       12   perchloroethylene, above formaldehyde, above
       13   chloroform, above acid aldehyde, methyline chloride,
       14   and even asbestos.  
       15                 And we can get into lots of arguments
       16   about how much asbestos people are exposed to on a
       17   day in/day out basis and so on and so forth, but
       18   we've never questioned any chemical -- we have never,
       19   ever, ever done an analysis of the exposure to the
       20   substance and used that as a criteria for defining as
       21   a toxic air contaminant.  Never.
       22                 DR. FUCALORO:  Really?
       23                 DR. FROINES:  Until today.
       24                 DR. FRIEDMAN:  Well, isn't that how the
       25   unit risk is determined, by the measure of how much

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   exposure people are going to have?  
        2                 DR. FROINES:  No.  
        3                 DR. FRIEDMAN:  Did I misunderstand how
        4   the unit risk is calculated?  
        5                 DR. FROINES:  No, you're dealing with a
        6   theatrical exposure versus an actual exposure.
        7                 DR. FUCALORO:  Yeah.  The unit risk is
        8   a number that is purely based upon inherent toxicity. 
        9   In order to get the danger to the population, you
       10   must multiply that by the dose.  
       11                 So what you're concerned about -- a
       12   real concern and something we -- all but you
       13   missed -- I missed it too -- was that this is
       14   unusual.  This is a pesticide.  People don't normally
       15   expose to it over an entire lifetime.  
       16                 But you would take that potency
       17   factor -- if you noticed the units are in inverse
       18   micrograms per meter cubed, and multiply it by dose
       19   which would be in micrograms per meter cubed, and to
       20   the first approximation that multiplicant will give
       21   you the probability that that would have the effect
       22   we think it has.
       23                 So if you multiply the two together and
       24   you come up with .1, that means you'd have a 10
       25   percent chance -- 10 percent to the population in

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   a -- of a million people in a 70-year period would
        2   end up with cancer.  Now, of course that would be a
        3   horror, but normally the numbers are much lower than
        4   that, thank God.  
        5                 DR. FRIEDMAN:  But that milligrams per
        6   kilogram, whatever, isn't that assumed that there's a
        7   certain duration?  I mean, is that for a millisecond
        8   or is that -- 
        9                 DR. FUCALORO:  Right.  
       10                 DR. FRIEDMAN:  Is that for a
       11   millisecond?  I think there's a duration that gets
       12   built into that.  
       13                 DR. FUCALORO:  You're right.  
       14                 DR. FRIEDMAN:  And I think the duration
       15   they assumed is a lifetime exposure at that level,
       16   which is not going to happen.
       17                 DR. FUCALORO:  That's right.  
       18                 DR. FROINES:  But that's still not the
       19   point.  The point is --
       20                 DR. FUCALORO:  Yeah, you're right about
       21   that.  
       22                 DR. FROINES:  -- that you calculate the
       23   number of cancers that would derive from a certain
       24   exposure to a certain population.
       25                 DR. FRIEDMAN:  For a certain length of

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   time?
        2                 DR. FROINES:  Yes.
        3                 DR. FUCALORO:  Yes.  
        4                 DR. FRIEDMAN:  And the length of time
        5   they assumed here is a lifetime of exposure.
        6                 DR. FROINES:  But the point is to
        7   determine the actual risk to the population, you take
        8   into account the timing and magnitude of the
        9   exposure.  This is a potency value.
       10                 DR. FRIEDMAN:  But there's got to be a
       11   time factor.  Are you saying that exposure -- this
       12   potency --
       13                 DR. FROINES:  I'm saying if this is --
       14   the unit risk for say diesel exhaust is 3 times 10 to
       15   the minus 4, if you assume that -- per microgram per
       16   cubic meter -- let's assume we have a microgram per
       17   cubic meter -- and you assume that people in L.A. --
       18   there are 20 million, and you multiply 20 million
       19   times 3 times 10 to the minus 4, you calculate the
       20   number of cancers you would expect for a 70-year
       21   lifetime of breathing diesel exhaust.  
       22                 Now, if you go and say people breathe
       23   diesel exhaust one time a week for six hours a day,
       24   when you do the calculation, you'll come up with a
       25   different number of people who will develop cancer. 

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1                 In other words, you plug in the actual
        2   exposures into this value to determine the population
        3   size at risk so that this is a -- this is a -- in a
        4   sense a slope.  This is a risk per microgram per
        5   cubic meter, but then you put in the exposure to
        6   determine the actual population base risk.
        7                 DR. FRIEDMAN:  There's no duration at
        8   all in this unit risk?  In other words, that exposure
        9   for one second is the same as exposure for a
       10   lifetime?  
       11                 DR. FROINES:  That's not where you take
       12   that into account.
       13                 DR. FUCALORO:  You know, I think you're
       14   right.  I think what these -- the inherent -- what's
       15   implicit in here is ambient concentration which means
       16   continuous exposure.  Am I correct?  That's implicit
       17   in this number.  
       18                 But Dr. Friedman is pointing out a
       19   point that I really don't know the answer to -- but
       20   it's something I missed, and he may be right -- is
       21   that for pesticides it may not be the right way to
       22   go, that people don't really experience that ambient
       23   concentration over their lifetimes.  I mean, I --
       24                 DR. FROINES:  But this is -- come on,
       25   guys.  Get back to the science.  When you -- it

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   doesn't happen for anything.
        2                 DR. FUCALORO:  True.  That's true too.
        3                 DR. FROINES:  It doesn't happen for
        4   anything.  But you take that into consideration when
        5   you calculate the population at risk.  And so this is
        6   not a -- look it:  I think that there is a mistake
        7   being made in terms of not understanding what the
        8   second step of this process is.  
        9                 Because if the value of the -- if you
       10   take the unit risk value and you're exposed one hour
       11   per day, 30 days a year to .001, the number of people
       12   at risk could be vanishingly small.  
       13                 And the risk manager can say, "Okay. 
       14   I'm not going to do anything about this."  Your
       15   risk -- your exposure assessment guides your risk
       16   management strategy.  The risk -- actual exposures do
       17   not guide the risk assessment process.
       18                 DR. FUCALORO:  Yeah, I think -- you
       19   know, in a way I think you're assuming I'm
       20   disagreeing with you.  I'm really not in this regard. 
       21   I think what he's pointing out and I think's
       22   correct -- I don't think there's a disagreement
       23   here -- is that with pesticides the exposure's more
       24   complex in general.  It's complex -- let me say it's
       25   complex in general but it's more complex in

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   particular for pesticides, I would think.  
        2                 This is just a guess because, you know,
        3   they spray in the spring.  Of course diesel exhaust
        4   concentration probably varies seasonally also.  But I
        5   would guess that pesticides would vary even more
        6   seasonally than say diesel exhaust, to use that as an
        7   example.  
        8                 DR. FROINES:  But Tony, all along
        9   Paul Gosselin could give you a very articulate speech
       10   in which he said 1807 is not even relevant to
       11   pesticides because pesticides are not ambient
       12   chemicals in the atmosphere.  Therefore, we got put
       13   in this law and we shouldn't even be here in the
       14   first place.  I've heard that argument for the last
       15   15 years from DPR.
       16                 MR. GOSSELIN:  That wasn't the
       17   argument.
       18                 DR. FUCALORO:  There he goes.  Froines'
       19   setting up straw men again.
       20                 MR. GOSSELIN:  Part of the argument is
       21   that the pesticides to at least something are
       22   inherently toxic than they are designed to be so.  I
       23   think we have fully found that there are some
       24   pesticides particularly with fumigants that are in
       25   the ambient air.  The other side of that is that the

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   pesticides are regulated, which goes to the argument.
        2                 All that aside, sort of the argument
        3   that we historically had about consideration of
        4   exposure wasn't something that necessarily totally
        5   came out of just our own institutional preference. 
        6   It was something that was put into the law.
        7                 DR. FROINES:  Yeah, exactly.
        8                 MR. GOSSELIN:  So the document, the way
        9   it's been designed, has been crafted in a way to
       10   comply with all the points in the law on how we're
       11   supposed to provide this document to you to evaluate. 
       12                 And we also have regulation that's
       13   specifically, and that's when I put the draft
       14   together, Bill actually provided me with a couple of
       15   examples that I tried to craft as closely as possible
       16   trying to lead in with what specific statutory and
       17   regulatory language we have for pesticides under
       18   1807.  But Bill's --
       19                 DR. FROINES:  We've been through that
       20   before, and we don't agree on those pathos.
       21                 MR. GOSSELIN:  Right.  But Bill's point
       22   too, is that what principally is the evaluation of
       23   whether this document has taken into account all
       24   scientific knowledge to assess the relative risk of
       25   this pesticide and to come back with us and present

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   findings.  And it is your findings.  So --
        2                 DR. FROINES:  That's my point.
        3                 MR. GOSSELIN:  Right.  So there's no
        4   disagreement there.
        5                 DR. SEIBER:  Anyway, let me just add a
        6   couple things here.
        7                 DR. FROINES:  Can we just have George?  
        8                 DR. SEIBER:  Oh, okay.  Go ahead. 
        9   Excuse me.  
       10                 DR. ALEXEEFF:  Let me just --
       11   George Alexeeff to clarify a couple of things.  
       12                 Okay.  Dr. Friedman is right and I
       13   think it's right over here in the sense that the
       14   table that we're referring to is a unit risk per
       15   lifetime.  And that's simply to normalize all of
       16   those numbers so that all the numbers can be compared
       17   as to how potent of a carcinogen it is.
       18                 DR. FUCALORO:  Inherent potency.  
       19                 DR. ALEXEEFF:  Inherent potency of the
       20   chemical.  That's issue No. 1.  
       21                 Issue No. 2 now comes to exposure. 
       22   Now, for the pesticides there is a -- on an annual
       23   basis a periodic exposure.  They have made an
       24   assessment in this document of a certain number of
       25   exposures occurring; a certain number of applications

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   and a certain number of exposures.  
        2                 I think it's three or I forget how many
        3   it is throughout the year, and then they've averaged
        4   that number throughout the year.  So the actual
        5   exposure concentration during that time period is
        6   higher.  They average it over 365 days.  Okay.
        7                 Now, the next assumption that is made
        8   is that that community will have those several
        9   applications each year for 70 years.  So that is
       10   where the issue comes in, I think, in part of what
       11   your concern is.  And this is an issue that comes up
       12   whenever we're referring to a more site specific kind
       13   of a problem.  
       14                 And you'll see in one of the three
       15   documents that we're bringing up this year where we
       16   actually come up with -- although we calculate unit
       17   risks for 70 years and we actually are evaluating a
       18   problem, we could actually consider other time frames
       19   in terms of actual potential.  
       20                 Where there's a need for mitigation or
       21   management, different time frames can be considered
       22   when you actually look at the specific site.  I'm not
       23   saying that's what DPR does, but I'm just saying that
       24   you're right.  
       25                 It's 70 years is the potency, but the

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   application -- it's not assuming that applications
        2   are occurring every day.  I think that's the major
        3   thing.  It's assuming they've only occurred in the
        4   normal agriculture use and they're averaged over the
        5   years.
        6                 DR. FUCALORO:  And in fact, you have
        7   several categories -- I'm just looking at my notes. 
        8   I have to always read them because you tend to write
        9   in abbreviations.  AADD:  the annual average daily
       10   dosage.  
       11                 And that would be useful for these long
       12   chronic sorts of things.  The acute ones of course
       13   you'd be more interested in some of the others: 
       14   seasonal average, daily dosage, and others of that
       15   type.  
       16                 So these organizations make note of the
       17   fact that some dosages are important to look at the
       18   average over a year and then extend it to 70 years. 
       19   This is the cancer potency in general so --
       20                 DR. FROINES:  Jim wanted to comment.
       21                 DR. SEIBER:  Well, I think George
       22   pretty much stated what I was going to state.
       23                 I think DEF's in its right place on
       24   this table on a unit risk point of view.  But I think
       25   what Gary and I and maybe others would like to see is

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   another column over here which takes the exposure
        2   which you multiplied by the unit risk to get the
        3   number of somethings in a population on a per million
        4   basis.
        5                 And I think if you did that -- it's not
        6   part of this table, but if you did that, you would
        7   find that DEF is at the margin at best, and we could
        8   probably debate whether it's below the cutoff, you
        9   know, off the page, or above.  And that would be an
       10   interesting discussion.  I'd like to have that.  
       11                 But it's not part -- as John points
       12   out, the law drives us in a certain way.  I disagree
       13   with it.  I think you've got to look at the whole
       14   range -- when you make a recommendation to the board
       15   that something ought to be done, you've got to look
       16   at the whole slate.  
       17                 Now, actually, our findings have all
       18   that in it, but the bottom line, the last one that
       19   John's referring to, do we or don't we want to
       20   classify this as toxic air contaminant, really comes
       21   back to where it is on the unit risk chart.
       22                 DR. BYUS:  No, no.  Not at all.
       23                 DR. FROINES:  Never has, never will.
       24                 DR. BYUS:  It has nothing to do with
       25   it.  Read page 78, paragraph 3.  Okay?  Page 78,

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   paragraph 3 explains very nicely in the document, I
        2   might add, the calculation of the risk.
        3                 If you go to the findings, the findings
        4   state quite nicely what the overall carcinogenic risk
        5   is for the population.  And they say, if you read
        6   finding No. 31, 
        7                    "For non threshold toxic
        8           endpoints one in a million risk
        9           typically represents the negligible
       10           risk standard.  Therefore, according
       11           to the criteria established in
       12           regulations, pesticides with risks
       13           greater than 10 to the minus 7 should
       14           be identified as toxic air
       15           contaminants."  
       16                 And this is 3.9 to 7 times 10 to the
       17   minus 7.  So it's just barely over what the threshold
       18   is.  Okay?  And that qualifies the risk for the
       19   findings.  
       20                 DR. SEIBER:  That's what I said.
       21                 DR. BYUS:  So that's really qualified
       22   in the findings.  It's qualified.  We can put it in
       23   there if you'd like.
       24                 DR. FUCALORO:  It's not only qualified,
       25   it's quantified.  And what Jim is suggesting and --

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1                 DR. BYUS:  Is another table.
        2                 DR. FUCALORO:  Well, is another column. 
        3   And you know, if you do it with a spreadsheet, you
        4   can sort them as opposed to unit risk factor or
        5   overall risk which would be the unit risk factor
        6   multiplied by the dosage.  And that would -- and that
        7   would, I think, you know -- and this is where
        8   reconciliation to all our opinions really is at the
        9   heart here.
       10                 DR. FROINES:  No.  No.  
       11                 DR. FUCALORO:  You don't agree?
       12                 DR. FROINES:  I think an absolutely
       13   fundamental issue is being lost here.  And it is an
       14   issue which -- as having been on this panel for
       15   15 years, it is an issue which has been argued and
       16   argued and argued vehemently during that entire
       17   period of history.  
       18                 And this panel until today has always
       19   taken the same position.  It has always taken the
       20   same position, and that is we do not consider
       21   exposure -- actual exposure as a criteria for
       22   defining whether a substance is a toxic air
       23   contaminant or not.
       24                 DR. FUCALORO:  But that's not what
       25   anyone's saying.  That's not what I'm saying anyway. 

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   I'm agreeing with you.
        2                 DR. FROINES:  The point is -- my point
        3   is let's take Jim's suggestion.  And we have a table
        4   on the right, and it -- we get down to DEF and we
        5   find that the actual risk to the population is
        6   vanishingly small.  Okay?  And in fact if you take a
        7   lot of these compounds, you might find that's the
        8   case.  
        9                 With DEF it's going to be very small
       10   and the numbers are 7,000 below or 3,000 or whatever
       11   the actual numbers are.  All right.  You've got the
       12   table.  Everybody's happy.  You've seen it.  
       13                 It doesn't look very important.  One,
       14   we don't know if next year somebody goes out and
       15   sprays pesticides and they spray a whole hell of a
       16   lot of it and the exposure levels go way up and that
       17   table is no longer relevant because the exposures are
       18   very high.  Does that mean that we come back and
       19   reconsider that as a toxic air contaminant?  No.  
       20                 The reason we have always only based
       21   our designation of a toxic air contaminant not on the
       22   actual exposures is because the inherent toxicity has
       23   been the defining criteria.  
       24                 And if you assume on a static basis, on
       25   the basis of Jim's study in Fresno and the other

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   study by Kilgore, that that defines the ambient
        2   exposures and we decide whether that that should,
        3   therefore, not be a toxic air contaminant, we, in a
        4   sense, are buying into the level of science on
        5   exposure as it currently exists.  And that has never
        6   been the policy of this panel.  
        7                 We've said that irrespective of that
        8   last column that Jim's talking about -- and I think
        9   it's fine -- that we will -- irrespective of that
       10   last column we're going to call DEF a toxic air
       11   contaminant.
       12                 DR. FUCALORO:  Yeah.  And I think the
       13   law is clear and says -- and, again, puts a very low
       14   hurdle to clear in order to designate something as a
       15   TAC, and I think DEF falls well within those
       16   parameters.  
       17                 However -- and that's the risk
       18   assessment which not only includes inherent
       19   toxicity -- in this case a cancer potency factor --
       20   but also dosage.  That's the health assessment --
       21   rather risk assessment.  
       22                 Then risk management really needs to
       23   know those numbers not only to potency but exposure. 
       24   They need to know that.  And we're validating that
       25   also.   

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1                 Don't forget these reports not only
        2   include the publication of -- in the case of cancer,
        3   a cancer potency factor, but also dosage -- estimated
        4   dosage levels.  And that's useful to the people who
        5   are responsible for risk management after assessment
        6   has been completed.
        7                 If you misunderstood me in saying that
        8   because the dosage is pretty low for DEF that I am
        9   suggesting we don't designate it a TAC, you have me
       10   wrong on that.  
       11                 Because I think that -- again, I read
       12   that law several times because I couldn't believe how
       13   low the thresholds were in order to designate
       14   something a TAC.  
       15                 And so I think DEF and my guess is
       16   almost any darn thing they bring before us will be
       17   designated a TAC by the law, within the parameters of
       18   the law.  And that's the thing I urged at the
       19   beginning, is the important thing has to be in the
       20   priorities in bringing things to us.  That's ---
       21                 DR. FROINES:  Let me just say one more
       22   thing about this:  Is that we have a policy on the
       23   panel that we designate things as toxic air
       24   contaminants based on the risk assessment.  
       25                 And Gary's raising a different issue. 

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   Gary is saying that things should be declared --
        2   determined toxic air contaminants based on the
        3   existing exposure estimation --
        4                 DR. FRIEDMAN:  Can I clarify something?  
        5                 DR. FROINES:  Let me just finish my
        6   thought.  
        7                 And all I'm saying is we can do
        8   anything we want.  We can change our policy and have
        9   the designation be defined by exposure and unit risk. 
       10   But we've never done that before.  So that's what we
       11   have to deal with.  
       12                 DR. FRIEDMAN:  I just want to say that
       13   I would like to thank Craig and others, because I
       14   misunderstood what the potency was, and Craig pointed
       15   out the definition of oncogenicity and so on on page
       16   78.  
       17                 And I didn't think this -- because of
       18   my previous misunderstanding, I didn't think that
       19   this was -- the measure for DEF was comparable to the
       20   others, but I now understand that it is.  And so I
       21   want -- for the record want to say that I withdraw my
       22   previous concern about that.
       23                 DR. FUCALORO:  I move that we expunge
       24   the record for the last 15 minutes.
       25                 DR. SEIBER:  I don't think we should

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   expunge it, because, you know, all this said -- and
        2   as I say, it's in the right place.  I'm glad they put
        3   the table together.  But to put things in perspective
        4   it's also nice to do the wedding, the marriage, of
        5   the exposure and unit risk.  
        6                 Now, the law doesn't tell us we have to
        7   do that.  No, you're right, it doesn't tell us.  And,
        8   yes, the DEF usage can go way up.  But the fact of
        9   the matter with this specific chemical it isn't going
       10   to go way up because it's used on one crop and
       11   they're not going to expand the acreage, it's just
       12   not going to happen.  There's 30 years of experience
       13   that says that's not going to happen.  So it's a
       14   little bit different than the other chemicals.
       15                 MR. FROINES:  We're not talking about
       16   DEF here.  We're talking about a fundamental policy
       17   decision on pesticides.  Make no mistake about it. 
       18   You change the way you do things and you're not just
       19   talking about DEF.  
       20                 Maybe DEF is the most irrelevant
       21   chemical that we'll ever have to worry about, and I
       22   tend to think that's probably true.  But we have to
       23   be careful when we make decisions about what the
       24   implications are for other substances where it may
       25   not be quite so clear.

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1                 So once we go down the slippery slope
        2   and say we're going to have this table over here and
        3   we're going to decide whether to recommend it as a
        4   toxic air contaminant based upon what these numbers
        5   multiply out to be, we've made a pretty fundamental
        6   policy decision.  
        7                 And I don't think we should -- I
        8   personally do not think we should make that decision. 
        9   I think we should -- I think we should -- Wells can
       10   do whatever he pleases because it's his prerogative. 
       11                 But I think -- here's the issue for us: 
       12   The issue for us is what the panel recommends, what
       13   we say.  We say DEF should be declared a toxic air
       14   contaminant.  
       15                 We could also say but the director may
       16   want to take into account issues of exposure.  But
       17   I'd rather he took that into account rather than our
       18   taking it into account.  
       19                 Do you see what I'm saying?  
       20                 DR. FUCALORO:  Yeah.  But exposure, of
       21   course, is part of the document that we receive to
       22   approve.  Exposure is part of the document and has
       23   relevance.
       24                 Now, again, John, I don't think that
       25   that would in any way imaginable to me change a

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   designation from a TAC to a -- not to be a TAC or
        2   vice versa.
        3                 DR. FROINES:  We get exposure documents
        4   from ARB, and we never use them.  We never use them. 
        5   We get a full exposure document from ARB.  It has
        6   never been a basis for determining whether
        7   something's a toxic air contaminant.
        8                 DR. FUCALORO:  No, I understand that.             
        9   But it is a base for mitigation or risk management. 
       10   And it's our job to look at that and to make sure
       11   that the exposure estimate is scientifically
       12   reliable.  Yeah.
       13                 DR. FROINES:  But the panel has never
       14   done the following:  The panel has never taken part A
       15   from the ARB --
       16                 MR. FUCALORO:  Right.  
       17                 DR. FROINES:  -- and part B and said,
       18   "Before we decide to declare this a toxic air
       19   contaminant, we're going to multiply by what's in
       20   part A by what's in part B."  We could do that on
       21   every compound that's on this list.  
       22                 DR. FUCALORO:  Sure.  
       23                 DR. FROINES:  We have never done it. 
       24   It is not our policy to do so.
       25                 So if we -- and I'm saying I think we

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   shouldn't change that policy.  And so I think that
        2   the issue of whether or not the director decides to
        3   use the MOE for his decision making, that's another
        4   issue.  But for the panel I think we should stay with
        5   the policy we have.
        6                 DR. KENNEDY:  Well, I've fumed and
        7   stewed over this since my first attendance on this
        8   panel.  The internal tension here is that we -- we
        9   consider these data, we evaluate them, and then we
       10   sort of put them aside.  And I -- I too have always
       11   been uncomfortable about that but figure I'm sort
       12   of -- you know, I'm the new kid on the block.  So be
       13   it.  
       14                 I think what John is saying, you know,
       15   represents a very fundamental position of the panel
       16   and, you know, I'm willing to accept it and to go
       17   along with it.  But that doesn't alleviate a lot of
       18   my discomfort along the way.  I just have to figure
       19   out how to live with it.
       20                 DR. FUCALORO:  Well, hearing that no
       21   one is prepared to have a panelist revolt, maybe we
       22   should move on.
       23                 DR. FROINES:  Maybe we should take a
       24   break.  Take a break and go back and start over
       25   again.

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1                 (Recess.)
        2                 DR. FROINES:  One of the issues is that
        3   Craig has to leave in about 45 minutes, I think.
        4                 DR. BYUS:  No, no, no.  Quicker than
        5   that.  In about 20 minutes.  
        6                 DR. FROINES:  Twenty minutes.  
        7                 DR. BYUS:  For an hour.
        8                 DR. FROINES:  So why don't we leave the
        9   policy decisions until later and any technical issues
       10   that we want to take up with respect to DEF at this
       11   point.  
       12                 So Craig, why don't you take the lead.
       13                 DR. BYUS:  All right.  I just have --
       14   well, my one issue was the serum cholinesterases
       15   value and calculating the NOEL.  And that's a larger
       16   topic.  
       17                 It's not a problem with methyl
       18   parathion, which is also an organophosphate, and
       19   we'll get into that later on this afternoon.  It's
       20   not a problem in that calculation.  
       21                 I don't really think it's a large
       22   problem because it doesn't really change the NOELs
       23   very much at all and even hardly significantly in the
       24   document as it is now.  I think it's an important
       25   concept, though.  I've talked to you about it in some

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   detail.
        2                 But I do want to -- you did put in on
        3   page -- on your revised documents under "Background,
        4   Mechanism of Action," you make this statement at the
        5   end dealing with what the function of --
        6                 DR. FROINES:  What page?
        7                 DR. BYUS:  I don't know what page it's
        8   on now.  This is the -- gosh, I -- it's the -- this
        9   is the changes that were faxed to us.
       10                 DR. SEIBER:  Are you talking about the
       11   findings or the actual --
       12                 DR. BYUS:  The actual document.
       13                 MR. GOSSELIN:  What section?
       14                 DR. BYUS:  I don't know.  You sent it
       15   to me so -- it says "Background," under "Mechanism of
       16   Action."  I think it's -- well--
       17                 MR. GOSSELIN:  I think I got it.
       18                 DR. BYUS:  I don't know exactly where
       19   it falls in the new purple one.  
       20                 But the point is it says -- you 
       21   say,        
       22                    "In addition to plasma it is
       23           also" -- this is being the serum
       24           cholinesterase -- "is present in the
       25           liver, lung, and other organs,

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1           although its physiological function
        2           is unknown."  
        3                 I took some issue with that, and I
        4   still think that it's -- there are functions for it. 
        5   And we've discussed -- you know, we can discuss it in
        6   terms of metabolism, drugs.  There's a large function
        7   for it, whether you want to call that physiological
        8   or not, I don't know.  
        9                 But my main -- and then you put in a
       10   nice little discussion about the atypical genetic
       11   variants of plasma cholinesterase.  And these people
       12   are usually very sensitive to succinylcholine
       13   anesthesia, and these people die and go into
       14   prolonged apnea.  
       15                 And that was good that you put that in
       16   here and actually came up with something I never
       17   thought about, whether or not if you are an abnormal
       18   pseudo-cholinesterase person, do you then have
       19   abnormal sensitivity to organophosphates.  That was
       20   actually nice to put in here.  
       21                 The thing I disagree with -- and I just
       22   want to tell you because I haven't had a chance to
       23   see you -- is it says at the end, 
       24                    "It was unlikely that plasma
       25           butyrylcholinesterase or erythrocyte

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1           acetylcholinesterase would offer
        2           significant protection again paraoxon
        3           toxicity."  
        4                 And in a literature search I did it
        5   actually does offer protection.  I mean, I have a
        6   reference here, and it says, 
        7                    "Human butyrylcholinesterase
        8           has previously been shown to protect
        9           mice, rats, and monkeys against
       10           multiple lethal toxic doses of
       11           organophosphate and organophosphorous
       12           acetylcholinesterase.  
       13                 DR. KENNEDY:  That's old stuff.
       14                 DR. BYUS:  Well, yeah, it's old.  But
       15   it's different than what it says here.  I'm just
       16   saying that it apparently does protect.  I mean,
       17   that's not really the point, but this statement in
       18   here is wrong.  So just delete this last sentence.  
       19                 You say, 
       20                    "The investigators concluded
       21           that based on the results with plasma
       22           acetylcholinesterase, it was unlikely
       23           that plasma butyrylcholinesterase or
       24           erythrocyte acetylcholinesterase
       25           would offer significant protection

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1           against paraoxon toxicity."  
        2                 MR. GOSSELIN:  I think the statement
        3   was just parroting back what was out of that paper.
        4                 DR. BYUS:  Right.  And I'm telling you
        5   from what I've read is that that statement isn't
        6   correct.  So we might as well make it correct.
        7                 MR. GOSSELIN:  Would you like us to
        8   take that sentence out?  
        9                 DR. BYUS:  Just delete it.  Delete it. 
       10   And you -- well -- 
       11                 DR. SEIBER:  Could I ask you a question
       12   about where we are in our discussion?  I got a copy
       13   of what appears to be a revised set of findings from
       14   the DPR group this morning.  Is this -- Paul, is
       15   this --
       16                 MR. GOSSELIN:  Yeah, those incorporate
       17   the comments you sent in to me.
       18                 DR. SEIBER:  Did you get any, other
       19   comments that are incorporated in here?
       20                 MR. GOSSELIN:  Bill Lockett sent in
       21   some comments and some issues.  I spoke with
       22   Dr. Witschi, and he didn't have any other than he
       23   thought it was too long, and that was about it.
       24                 DR. SEIBER:  Okay.  Well, I guess my
       25   suggestion is that we -- unless people have some more

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   on the actual documents -- which I haven't read these
        2   purple ones either, so I don't know.  We just got
        3   these this morning too.  
        4                 But it seems to me the most important
        5   thing is to go back and check out these -- the
        6   findings that are recommended for us to look at,
        7   because that's really what we've got to come up with.
        8                 DR. FROINES:  Yeah.  But before we do
        9   that, Craig, are you finished?  
       10                 DR. BYUS:  I'm pretty much finished,
       11   yes.
       12                 DR. FROINES:  I want to give everybody
       13   a chance to deal with the substance before we go to
       14   the findings.
       15                 DR. BYUS:  They did make some
       16   significant number of changes to the document based
       17   upon what people had said and what OEHHA had said,
       18   and they faxed us these changes specific -- I mean, I
       19   don't know where they fit in but -- so I mean
       20   that's -- it's worth considering them, I mean, the
       21   fact that they did make these changes in response to
       22   the criticism and put them in a document, in a brand
       23   new document, very quickly.  
       24                 And I just tried to go over it for
       25   consistency, but I have only managed to go through

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   part of it.  But it appears to be a pretty good
        2   response to what was stated.
        3                 DR. SEIBER:  And I already said my
        4   peace about the table that they put in.  I think
        5   that's a good addition, and I appreciate your putting
        6   that in the document.
        7                 DR. FROINES:  Which table are you
        8   referring to?  
        9                 DR. SEIBER:  The one with the -- all
       10   the unit risks for all the SRP declared TACs.
       11                 DR. BYUS:  My question would be:  Is
       12   the California Department of Health Sciences -- is
       13   George happy with the changes that were made in
       14   response to his -- he also prepared a very large,
       15   extensive list of criticism or suggestions, and many
       16   of them, it appears, were incorporated in here.  
       17                 So are you happy, George?  That's what
       18   I -- that was my question.  
       19                 DR. ALEXEEFF:  Yeah, I also just
       20   checked with staff.  All of our changes have been
       21   incorporated, so we're fine.
       22                 DR. BYUS:  So I think that's it worth
       23   to be stated for the record, that all of these
       24   changes were incorporated in the new, revised
       25   document that's before us, and now we can discuss the

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   findings or in case anyone else has any except for
        2   that one strange thing I found but --
        3                 DR. SEIBER:  Again, just a quick
        4   commentary.  I think it's very good that DPR and
        5   OEHHA and ARP -- the system seems to be working.  I
        6   mean, we've had places where it hasn't always worked
        7   in the pesticide areas, but I want to state for the
        8   record that it appears to me the system is working,
        9   and I'm very pleased with it.
       10                 DR. BYUS:  Me too.
       11                 DR. GLANTZ:  I'm just --
       12                 DR. FROINES:  Peter.  
       13                 I'm going around the room.  We'll get
       14   to you.  
       15                 DR. GLANTZ:  Okay.  I don't have a lot
       16   to say.
       17                 DR. FROINES:  But it's always so
       18   choice.
       19                 Peter.
       20                 DR. KENNEDY:  No, I'm fine.  I think
       21   that we've come a long way since that first session,
       22   and I'm comfortable.
       23                 DR. FROINES:  Gary.
       24                 DR. FRIEDMAN:  I have nothing to add.
       25                 DR. FROINES:  See.  It didn't take long

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   to get to you.
        2                 DR. GLANTZ:  Okay.  Well, actually, I
        3   also thought -- I only reviewed the changed things
        4   you sent, but those look fine.  I only had just one
        5   little thing about the executive summary.  
        6                 In all of the other ones that we've
        7   done at the end, it said, "Should DEF be listed as a
        8   toxic air contaminant," and that got left out.  And I
        9   think it should say, "Yes."  
       10                 Sort of you can get the OEHHA or the,
       11   you know -- I don't know if anybody's got one of the
       12   reports from before that we went through with ARP,
       13   but you could just copy that last little section and
       14   change that to DEF.
       15                 DR. FROINES:  We'll come back to that. 
       16   We haven't finished that discussion.
       17                 DR. GLANTZ:  And also I think we
       18   usually put the table that was put in -- you know,
       19   where DEF was listed with the other things, didn't
       20   that usually go in the executive summary too?  So I
       21   suggest that.  But it terms of the content of the
       22   report I agree with Craig.  I think you did a nice
       23   job in responding to all the criticisms.
       24                 DR. FROINES:  Wake up.
       25                 DR. FUCALORO:  Oh.  Call my name.  For

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   the record, he wasn't asleep he was pondering his
        2   notes.
        3                 Just a -- just to make me feel
        4   comfortable with this, the AADDs were purely
        5   one-sixth the SAAD; is that right?  That's how they
        6   computed; right?  Just something like that.
        7                 MR. GOSSELIN:  Yes.
        8                 DR. FUCALORO:  That's all I have.
        9                 DR. SEIBER:  I said my peace out of
       10   turn.
       11                 DR. FROINES:  Okay.  Well, I wanted to
       12   make a couple of comments.  One problem -- and it
       13   occurs in almost all government reviews of
       14   chemicals -- is there's a section where people --
       15   that's called toxicokinetics or pharmacokinetics. 
       16                 And people go through and they take all
       17   the studies that have occurred, and they look at
       18   absorption, distribution, excretion, metabolism, and
       19   they look at it in terms of dermal and inhalation. 
       20   So you know what I'm talking about.  
       21                 Most of those studies, most of those
       22   sections in those reports end up being totally
       23   unreadable by any normal human being because what
       24   they represent is a series of studies.  
       25                 But what I want to know is if you found

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   a cancer in the colon, what is the distributional
        2   information available on that chemical that gives
        3   biological significance to finding cancer in the
        4   colon.  If somebody's got a C14-labeled study and
        5   they haven't found any C14 in the colon, you have to
        6   say what's going on here.
        7                 In other words, the toxicokinetics,
        8   whether you're looking at clearance or metabolism or
        9   distribution, all those things affect the biological
       10   nature of the outcome.  I mean, that's not said very
       11   well.  It affects the health outcome and justifies
       12   it.
       13                 So with MTBE and Maltony finds
       14   leukemias and lymphomas and we know that the stuff
       15   ends up in the spleen, we actually can say that's
       16   relevant toxicokinetics, finding the label in the
       17   spleen and thinking that actual spleen was an
       18   important source of the leukemia lymphoma, that that
       19   was an important use of the toxicokinetics.  
       20                 And I can go through this with your
       21   staff, but I think that we want to develop
       22   toxicokinetic sections that relate to health
       23   endpoints, is my take on it.  
       24                 So when you're in here and you're
       25   talking about the difficulty of going from hens to

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   humans, somebody has to write a thoughtful
        2   toxicokinetic section about what we know about hens'
        3   toxicokinetics for this compound and try and relate
        4   that to what you know about humans.
        5                 And so I think one of the long-term
        6   issues for us has to be that we don't just produce
        7   sections that are throwaways, because that's what
        8   they turn out to be, and that we actually try and
        9   link the information.  
       10                 And you folks should read our
       11   toxicokinetic section in there, in the MTBE document,
       12   because we have actually made an attempt to have the
       13   toxicokinetics be relevant to the health outcomes
       14   that we were studying as opposed to these long lists
       15   of studies that nobody ever can read and everybody
       16   always skips over except for the poor guy who wrote
       17   it.  
       18                 My -- the second question -- point I
       19   want to make is I think it's gotten made a little bit
       20   smaller, but this stuff in here about "Increase cell
       21   proliferation due to cytotoxicity can result in
       22   promotion of tumors by decreasing the time of elder
       23   repair of DNA damage, other genotoxic mechanism" --
       24   there's a whole bunch of rhetoric in here.  It's kind
       25   of the fashionable rhetoric.  

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1                 And I could give you an equal number of
        2   papers on the relationship between cell cycle
        3   apoptosis and genetic events to show that in fact
        4   that Emanuel Farber in Toronto has shown that cell
        5   proliferation in some cases is the reverse of what
        6   you might say in here.  
        7                 So I think we have to be careful to
        8   avoid the generally popular rhetorical stuff. 
        9   Because there's an awful lot of good molecular
       10   biology that would actually contradict some of this. 
       11   And I can be happy to provide references to that. 
       12   Bob Wineberg from MIT, Robert Wineberg, has been
       13   writing very articulately about that. 
       14                 The -- I think that the issue of what I
       15   hope we can get to in a few months is to not have you
       16   say "Not enough is known about the hen" and then
       17   basically it's -- you hand wave it away.  
       18                 I'd rather that we -- if it looks like
       19   the -- that, 
       20                    "While the hen feeding study
       21           has a 30-fold lower NOEL, there are
       22           some uncertainties in using it to
       23           establish an inhalation NOEL.  
       24                    "First, a cross-route
       25           extrapolation needs to be performed. 

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1           Second, we need to have a little
        2           experience with quantitative
        3           extrapolation from hens to humans."
        4                 So we have a public health issue here. 
        5   We have an issue where if you do the work, you get a
        6   30-fold lowered NOEL.  Well, we better figure out how
        7   do we do that, how do we deal with that
        8   scientifically.                So we take that
        9   finding and see where it takes us.  Do you know what
       10   I'm saying?  You can't just wish it away because we
       11   don't know quite how to handle the hen
       12   toxicokinetics.
       13                 And I wanted to ask George one -- if he
       14   had any position on the notion of doing the risk
       15   assessment from the high dose point.  And I can't
       16   quote you from in here, but the document basically
       17   says that, 
       18                    "It was not possible to
       19           accurately estimate the oncogenic
       20           potency or upper bound on the slope
       21           for small intestine adenocarcinomas
       22           or alveolar or bronchiolar adenomas
       23           because the slope estimate is zero
       24           when the tumor incidence is only
       25           increased at the high dose."  

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1                 What would be OEHHA's policy on that
        2   issue?  
        3                 DR. ALEXEEFF:  Could you let me know
        4   what page you're on?
        5                 DR. FROINES:  74.
        6                 DR. FUCALORO:  For the record, can you
        7   tell us what you're referring to on page 74, please?  
        8                 MR. FROINES:  This is in section 5 on
        9   "Oncogenicity," and there is a "Weight of Evidence"
       10   discussion --
       11                 DR. FUCALORO:  Okay.
       12                 DR. FROINES:  -- and a "Quantitative
       13   Assessment."  And the statement is:  
       14                    "It was not possible to
       15           accurately estimate the oncogenic
       16           potency (Q1) or upper bound on the
       17           slope (Q star) for small intestine
       18           adenocarcinomas and alveolar/
       19           bronchiolar adenomas because of the
       20           slope estimate as zero when the tumor
       21           incidence is only increased at the
       22           high dose."  
       23                 Therefore, they used the
       24   hemangiosarcomas to calculate the potency.  
       25                 DR. ALEXEEFF:  I guess the question or

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   I have to make an assumption about understanding the
        2   issue of the slope estimate is zero.  
        3                 Is that the Q1 is zero?  
        4                 UNIDENTIFIED SPEAKER:  Yes.  
        5                 DR. ALEXEEFF:  Is that what we're
        6   basically saying?  
        7                 UNIDENTIFIED SPEAKER:  Q1 asterisks.  
        8                 DR. ALEXEEFF:  Well, generally the
        9   procedures that we've used in this program is to rely
       10   more heavily -- specifically for this reason on the
       11   upper 95 percent confidence bound.  
       12                 Because when we have very few dose
       13   levels in any of these studies -- even a great study
       14   has three or four dose levels -- when you have so
       15   few, the estimate of the slope or the Q1 or the
       16   maximum likelihood estimate often can go to zero. 
       17   It's an unstable calculation.  
       18                 But the upper bound estimate on that
       19   slope is a stable calculation.  And so for that --
       20   that's what one of the major reasons that we have
       21   always emphasized the importance of the upper bound.
       22                 There have been a number of
       23   situations -- I'm trying to think.  I think acid
       24   aldehyde that came before the panel where one of the
       25   comments that was submitted was constantly

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   questioning why don't we focus more on the Q1 in that
        2   calculation.  
        3                 And one of the reasons was because if
        4   we changed one animal as to whether they had a tumor
        5   or not had a tumor, the MLE would go to zero.  And so
        6   it simply is a, for some reason, unstable
        7   calculation, I guess, in the extrapolation procedure. 
        8                 So I guess our -- I don't think it
        9   would ultimately change the result of the actual
       10   potency here.  In this case we would probably try to
       11   see if we could determine upper bound slope.  
       12                 But in a situation like this we would
       13   probably choose the tumor site that seemed to be the
       14   most stable in our calculations as opposed to
       15   choosing one that even though we don't use the Q1, it
       16   would be nice if we could, you know -- if it's
       17   calculatable based upon the data.
       18                 DR. FUCALORO:  Can I ask a question to
       19   follow up on that?  The decision to use Q1 asterisk I
       20   guess as the upper bound because of this difficulty
       21   with Q1, is that based upon -- I mean, you do it. 
       22   You said you do it.  But you are not a trained
       23   statistician.  
       24                 But are the statisticians in your
       25   office satisfied with that particular procedure?  

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1                 DR. ALEXEEFF:  Yeah, they are very
        2   satisfied.  And for the most part I think what is
        3   interesting is when you look at Q1 and Q1 star in the
        4   calculation, what is sort of the range between those
        5   two values.  
        6                 Like in this case if you look at for
        7   DEF, 9.2 for the Q1, which is the MLE 10 to the minus
        8   6 and then 1.6, you can see they're actually very
        9   close.  The upper bound is not far from the line
       10   here.  So it's a stable calculation.  
       11                 And you can actually look at a number
       12   of these.  So if you were obtaining upper bound
       13   values that were five- or tenfold different from the
       14   maximum likely estimates, then we would worry about
       15   what's happening in the calculations.  
       16                 So we don't think we're adding a lot of
       17   conservatism in sticking with the upper bound, but
       18   it's actually the statistical argument that our
       19   statisticians give us that it's more stable to stick
       20   with the upper 95% UB.  
       21                 DR. FUCALORO:  The reason I ask the
       22   question is that very often in use of statistics you
       23   can make a lot of mistakes, and that's why I really
       24   always want to check with someone who's an expert in
       25   the area before we proceed.  

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1                 DR. FROINES:  I just want to make one
        2   point about that just in terms of the future.  That
        3   was very helpful, George, and I don't mean to put you
        4   up as a straw person at all, but be careful about the
        5   writing being dismissive versus trying to explain the
        6   position in a thoughtful way.  
        7                 We all, when we're tired -- it's easier
        8   to get rid of things than to carefully define the
        9   reasons why you were doing what you were doing, and I
       10   think that will just improve the overall quality of
       11   the documents.  It's a minor point.  
       12                 DR. ALEXEEFF:  I think just as a
       13   follow-up, one of the -- and I can research this and
       14   come back at some point and talk about it.  One of
       15   the criteria that we use in our calculations is the 
       16   Chi square fit of the line to the points, and there's
       17   some other information that comes out in the
       18   analysis.  
       19                 And that's usually what we follow as to
       20   whether or not one can actually fit a legitimate line
       21   to those points.  I don't know what would happen for
       22   this particular data set, but that might be one way
       23   of looking at it that probably Chi square value would
       24   show it's not a good fit so --
       25                 DR. FROINES:  He just did that for your

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   benefit.
        2                 DR. FUCALORO:  Listen, I'm --
        3                 DR. FROINES:  He wanted to show he
        4   knows some statistics over there.
        5                 DR. FUCALORO:  Well, he knows more than
        6   I do if he knows any.
        7                 DR. FROINES:  Well, let's follow Jim's
        8   suggestion, and hopefully we might be able to try to
        9   finish this by the time we break, which is to go to
       10   the issue of the findings.  
       11                 Jim?  
       12                 DR. SEIBER:  Well, we just got the
       13   findings today, so we haven't had a chance to really
       14   read them in detail.  And I read them over, and from
       15   my point of view they've incorporated practically all
       16   the recommendations I had made in a fax that I sent
       17   to Paul, I believe, last week.  
       18                 And there's a few little typographical
       19   things that I've picked up in a very quick reading
       20   that we can maybe hand to you or something like that. 
       21   But really, John, aren't these our -- these are our
       22   findings at this point now.  We make the final
       23   changes.  We don't have to go back to the DPR.
       24                 So let me just be a little more
       25   specific.  Since I was the lead on the environment

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   fate and exposure part, I'll just comment on that and
        2   say that I agree with the points that are written
        3   down here in the draft findings with just -- again, a
        4   few minor things, one of which was a personal problem
        5   I have with No. 3 that says DEF breaks down by photo
        6   oxidation.  
        7                 It really isn't proven that it's photo
        8   oxidation.  That's one of several possible
        9   mechanisms.  So since we want to make sure our
       10   science is as right as we can get it, that's the kind
       11   of change that I'll write down and hand to you or to
       12   Paul.
       13                 MR. GOSSELIN:  Who actually handles the
       14   changes?
       15                 DR. FUCALORO:  A moment, please.  
       16                 If we're asked to approve the findings
       17   in this report, I think the best we can do today is
       18   provisionally, because we were just handed this
       19   thing, and I really -- I think we really require
       20   reading through it carefully.  
       21                 Now, we can, I suppose, do something
       22   which says if we have no objections by a time
       23   certain, maybe a week from now, it just goes forward. 
       24   But I do -- I'm not prepared to say definitely.  I
       25   just haven't read it and thought about it.

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1                 DR. GLANTZ:  Well, these are -- I
        2   should say they're pretty similar to -- how are these
        3   different from what you sent us a while ago?  They
        4   look similar to me.
        5                 MR. GOSSELIN:  Actually, it's largely
        6   the same with a lot of clean-up and edits.  The
        7   OEHHA's findings that were presented at the last
        8   meeting probably account for 80 percent of the
        9   findings.  
       10                 It was actually used as the foundation. 
       11   The beginning was changed with some of the
       12   environmental fate information and then the end with
       13   some of the specific references to the statutes was
       14   changed, and then the toning and thing was changed. 
       15   So it was essentially largely OEHHA's findings.  
       16                 DR. FROINES:  As a procedural matter
       17   what I would suggest based on Tony's comments is that
       18   we go through them now to the degree we can before
       19   lunch.  
       20                 We then say -- say after lunch we say,
       21   "Well, I want more time," and then we say if --
       22   "We'll give you until next Friday to get comments in
       23   and after that the barn door closes," essentially. 
       24   So just so we don't let it drag on.
       25                 MR. LOCKETT:  Mr. Chairman, I just

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   wanted to add that we're prepared today.  We have the
        2   revised findings on disk and have a computer here. 
        3   So as you make changes, we can update them and print
        4   them out.
        5                 DR. FROINES:  The findings I have here
        6   that are not -- have not incorporated Jim's changes.  
        7                 MR. LOCKETT:  Yes.  To my understanding
        8   is they have.
        9                 DR. FROINES:  Well, I'm looking at a
       10   set of findings here that I can tell you don't have
       11   the changes.
       12                 DR. GLANTZ:  Well, can I make a
       13   suggestion?  Why don't we go through and discuss what
       14   we have here and then maybe during the break you
       15   could make up a kind of red-line strike-out version
       16   that makes the changes obvious.  
       17                 Because my sense -- I mean, I didn't
       18   memorize them, but I did look at them when you sent
       19   them to me, you know, a couple weeks ago, and I
       20   didn't see any substantive changes between those and
       21   these, at least to the things I cared about.  
       22                 So maybe if you could during lunch make
       23   something up that highlights exactly what you changed
       24   from what you sent to us a couple weeks ago, that
       25   might facilitate things.  

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1                 DR. FRIEDMAN:  I would like to make
        2   that as a constructive suggestion for the future that
        3   if we could get -- you know, I read the findings on
        4   the plane coming down, the previous version, and if I
        5   could have just -- I'm sure that there's very little
        6   change.  If I could have just seen what the changes
        7   were when we were handed this, it would have made
        8   things much simpler.
        9                 DR. FUCALORO:  You mean a red-line copy 
       10   which --
       11                 DR. FRIEDMAN:  Yeah, something which
       12   shows what changes or additions were made.
       13                 DR. GLANTZ:  Anyway -- 
       14                 DR. FROINES:  There's a document that
       15   you apparently don't have --
       16                 DR. GLANTZ:  We'll pick this up at the
       17   door.  
       18                 DR. FROINES:  -- and we'll give it to
       19   you.
       20                 DR. GLANTZ:  It looks like the same
       21   thing.  
       22                 DR. FROINES:  Let's go through --
       23                 DR. GLANTZ:  This is the one at the
       24   door.
       25                 DR. FUCALORO:  Which is the latest

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   version:  the one at the door or the one which has at
        2   the upper right-hand corner "with Seiber's edits
        3   included"?  
        4                 MR. MATHEWS:  I wrote that.  
        5                 DR. FUCALORO:  What?  
        6                 MR. MATHEWS:  I wrote that in for you.
        7                 DR. FUCALORO:  Oh, you wrote that in
        8   for me.  I see.  
        9                 DR. GLANTZ:  Except that's different
       10   than the one at the door.  Because I picked this one
       11   up at the door, and it's different than the one he
       12   has.  
       13                 DR. FUCALORO:  Is this different?
       14                 DR. GLANTZ:  Yeah.  That's your
       15   writing.  
       16                 DR. FROINES:  Well, I think that what
       17   we need, Peter, is we need the most recent DPR draft
       18   with Seiber's changes included.  And that represents
       19   the most recent.
       20                 DR. SEIBER:  That's what I think I
       21   have.
       22                 DR. FROINES:  That's what I have.  
       23                 DR. SEIBER:  And John, I -- during the
       24   previous discussion, I just sat here and I went back
       25   and forth, and I saw that they had in fact made the

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   changes.  At some time my suggestion was vague.  I
        2   said reword the sentence, and they reworded it.
        3                 DR. FROINES:  Folks, we've got a
        4   problem here.  We've got to get this --
        5                 DR. GLANTZ:  Can I make a suggestion? 
        6   While the staff figures out what the latest version
        7   is -- because the one that he has and the one that I
        8   have which allegedly are both the latest version are
        9   different -- 
       10                 DR. FUCALORO:  At least printed
       11   differently.
       12                 DR. GLANTZ:  -- why don't we talk about
       13   the issues that are raised, because there are a
       14   couple of issues in here.  And then while we're
       15   talking about the things more generally, then the
       16   staff can figure out which one we want to actually
       17   approve or act on.
       18                 DR. FROINES:  Okay.  Does everybody
       19   have these with the handwritten comments?
       20                 DR. GLANTZ:  No.  
       21                 MR. MATHEWS:  I'm producing them right
       22   now.
       23                 DR. GLANTZ:  Okay.
       24                 DR. FROINES:  Okay.  Stan, why don't we
       25   go ahead with what you have in front of you.

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1                 DR. GLANTZ:  Okay.  Well, I just had
        2   one or two issues, one of substance, and it gets back
        3   to this NOAEL which I really dislike intensely.
        4                 The -- I'm very uncomfortable -- I
        5   mean, I was very pleased to see that the NOELs were
        6   added to the report as we requested last time and
        7   that they're in the findings.  
        8                 But to me I'm very squeamish about
        9   going along with this idea of a no-observed adverse
       10   level -- adverse effect level, because I think that's
       11   pretty subjective.  
       12                 And personally I would be a lot more
       13   comfortable if we took the NOAELs out of the
       14   findings.  If they want to leave them in the report
       15   for reference, I mean, I just as soon they weren't
       16   there too, but I can swallow that.  
       17                 But I mean, that's really a regulatory
       18   judgment.  And I am uncomfortable with us endorsing a
       19   regulatory position.  I mean, I'm willing to be
       20   talked out of it, but I would be more comfortable if
       21   those things were deleted.  
       22                 If you look through the findings, they
       23   have the NOAELs in each of the items.  It starts
       24   around number -- it's like No. 18 through No. 24. 
       25   And then it keeps going to 25.  So that's the one

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   change that -- the one substantive change that I'd
        2   like to suggest.
        3                 DR. FUCALORO:  There is a sentence in
        4   there which gives me pause.  I guess I don't mind the
        5   NOAEL and the NOEL both being reported, but they did
        6   say something which implies regulation.  It says
        7   "report would also provide the basis for risk" --
        8                 DR. GLANTZ:  What number are you on?  
        9                 DR. FUCALORO:  18.  -- "basis for risk
       10   management.  The inclusion of NOAEL provides the
       11   information required for risk mitigation."  So you
       12   may not like it, but it appears that they're using it
       13   for purposes of mitigation.  
       14                 Is that correct?
       15                 DR. GLANTZ:  No, I understand that. 
       16   But it just seems to me -- I mean, there's a certain
       17   amount of subjectivity as we talked about at the last
       18   meeting in the -- when you put the A in there.  And I
       19   just as soon let the risk managers take
       20   responsibility for that without pinning it on us,
       21   because I'm personally uncomfortable with it.  
       22                 I mean, I think the -- in terms of the
       23   risk assessment and the hazard identification the
       24   NOEL is the important thing.  And if DPR wants to
       25   say, "Well, we're willing to set -- we're willing to

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   accept a certain amount of adverse effects or effects
        2   because we don't think they're that important," you
        3   know, I think that's up to the regulators to do.  
        4                 But I personally would rather not have
        5   them saying, "Well, the SRP said this is the number
        6   that you should use."  Because I don't know if I
        7   agree with that number.
        8                 DR. SEIBER:  Well, I thought the NOEL,
        9   NOAEL debate relative to cholinesterase inhibitors
       10   was kind of an unsettled area, that there's people
       11   that kind of feel on both sides.  
       12                 And the way I understand it -- and I'm
       13   not a toxicologist -- is that you can demonstrate an
       14   inhibition but you can't show there's any adverse
       15   effect associated with that inhibition.  And that
       16   seems kind of important to me.  
       17                 So I don't know whether I'm ready to
       18   just take it out.  I think we ought to put it in
       19   perspective, but I don't know whether I'd want to
       20   just take it out of the document.
       21                 DR. GLANTZ:  I wouldn't take it out of
       22   the -- I'm willing to leave it in the document.
       23                 DR. SEIBER:  Or even in the findings.
       24                 DR. GLANTZ:  But I'd rather not have it
       25   in the findings.  

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1                 DR. FRIEDMAN:  If the pulse rate goes
        2   up two beats per minute, that's an effect, but it's
        3   not necessarily an adverse effect.  I don't see the
        4   problem with leaving in the adverse as a meaningful
        5   distinction of what's harmful and what's not.
        6                 DR. GLANTZ:  Well, anyway, what do you
        7   think?  Or what do the other guys think?  I mean, I'm
        8   not going to, like, kill myself over this, but it
        9   bothers me.
       10                 DR. FROINES:  Well --
       11                 DR. FUCALORO:  I'm sorry. 
       12   Clarification from Paul regarding how it's used for
       13   mitigation.  I mean, we certainly want to be on the
       14   record as accepting NOAELs as the best available
       15   information if in fact they're used for mitigation.
       16                 MR. GOSSELIN:  I think after the last
       17   meeting we went back and Dr. Glantz actually had a
       18   couple of comments that enlightened us about sort of
       19   where we were both talking maybe past each other
       20   about this document providing the best science that's
       21   known about assessing the risk of death.  
       22                 And you know, we've been using --
       23   pretty much preparing these documents for risk
       24   management purposes as a regulatory agency.  But for
       25   your purposes to look at the science, the NOEL, in

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   sort of its purest sense would be the plasma serum
        2   level, not the NOEL that we would typically use as a
        3   regulatory endpoint.  So we felt that it was
        4   appropriate to go back and make that distinction
        5   between the two.
        6                 And I think in each case you'll see
        7   it -- we do take a look at cholinesterase inhibition
        8   on a case-by-case basis.  And that's why we made the
        9   change here, to reflect that NOAEL would be the level
       10   that we would typically regulate from.  
       11                 But the report did have all the
       12   sufficient information to derive the NOEL where the
       13   lowest effect is seen, and that's in serum.  So I
       14   don't know if that answers your question.
       15                 DR. FROINES:  I -- here's what I
       16   think -- a late entry into the game:  The first thing
       17   is it would be useful if in the findings we
       18   actually -- and I don't see it, but I may -- I may be
       19   missing it -- if you defined and said, "For purposes
       20   of these findings, the NOEL is defined as blah, blah,
       21   blah.  For purposes of the findings, the NOAEL is
       22   defined as blah, blah, blah."  So you say to the
       23   reader what it is you are -- what your subsequent
       24   numbers are based on.  Now -- so that's just a point
       25   of clarification.

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1                 The question then becomes whether or
        2   not the NOAEL, NOEL for plasma cholinesterase is an
        3   adverse effect or not.  And apparently US EPA, from
        4   what Craig says, considers it an adverse effect. 
        5                 MR. GOSSELIN:  Actually, they did come
        6   out with their policy this week restating that they
        7   do use plasma cholinesterase, but they did, in their
        8   summary, allude that even though that didn't elicit
        9   an adverse effect, because of the potential of other         
       10   things, that's why they do use it.  So they even
       11   acknowledge that.  It's not -- it's still a very
       12   difficult complex.
       13                 DR. FROINES:  I understand.  I
       14   understand perfectly.  
       15                 Now, the fact of the matter is if one
       16   could relate, say, that the serum -- the plasma --
       17   the cholinesterase level with brain cholinesterase
       18   level, central nervous system levels, and you had a
       19   good sense of the relationship to the one exists,
       20   which probably there is one that exists, then you
       21   actually have a way to talk about one as a measure of
       22   an adverse effect rather than simply a measure of
       23   exposure because you think that the central nervous
       24   system effects do represent something that may have
       25   clinical implications so that what you're really

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   saying is that the linkage between a biomarker and a
        2   health outcome has not been quantitatively defined to
        3   everybody's satisfaction.  
        4                 MR. GOSSELIN:  I would say even further
        5   in this specific instance --
        6                 DR. FROINES:  I understand.  That's all
        7   I'm talking about.  I'm not talking about
        8   organophosphates in general.
        9                 And so but one could conclude that to
       10   the degree that an organophosphate producing an
       11   inhibition in blood may have implications for other
       12   target organs, that it is a potential marker of
       13   adverse effects.  
       14                 Having said all that, it seems to me
       15   that one could argue that it isn't simply a NOEL.  It
       16   is a -- at least a potential NOEL, NOAEL based on
       17   improved toxicokinetic understanding of the
       18   relationship between and validation of that
       19   relationship. 
       20                 Is that fair?
       21                 MR. GOSSELIN:  I believe so.
       22                 DR. FROINES:  Does anybody strongly
       23   disagree with that?  
       24                 DR. KENNEDY:  I sort of do.  I have
       25   some concerns about how far this goes.  I'm still

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   chewing on the issue of the hens.  Certainly, you
        2   know, the transition of information across species is
        3   an unknown, is an area of necessary additional
        4   research.  But on what basis do we make specific
        5   recommendations or directives for that sort of
        6   activity?  
        7                 I think similarly the -- although this
        8   potential exists, it has not been defined
        9   experimentally.  It's something that we perhaps would
       10   like to see, and is it -- is that sort of
       11   characterization within our purview?  Is it something
       12   that we need to include?  I don't know the answer,
       13   but I -- but I'm a little insecure about doing that.
       14                 MR. FROINES:  I think that it -- the --
       15   at some level we're talking about the validation of a
       16   biomarker for some other marker or endpoint.  And
       17   what's been said is that there is -- DPR saying is
       18   that "We think that there is inadequate validation"
       19   and the US EPA is saying, "Well, we think it may be
       20   somewhat better.  But as a policy decision it may not
       21   be better, but we're going to use it."  So we're
       22   talking about angels on the head of a pin here a
       23   little bit, I think.
       24                 MR. GOSSELIN:  This again is going to
       25   be -- I mean, we acknowledge that this is a real

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   complicated, important topic and is going to be
        2   probably one of the more interesting discussions
        3   we're going to schedule for the workshop.  
        4                 But I wouldn't -- on the other side
        5   too, I wouldn't categorize our position as an
        6   absolute position without viewing what the entire
        7   database shows for each compound.
        8                 DR. FROINES:  What happens if we take
        9   the NOEL as a NOAEL to your numbers?  
       10                 MR. GOSSELIN:  If you take the NO --
       11                 DR. FROINES:  If you take the NO --
       12   blood cholinesterase, how does it change your
       13   numbers?  
       14                 MR. GOSSELIN:  I still don't think
       15   it -- I think the MOEs is still over a thousand.  
       16                 DR. GLANTZ:  Uh-huh.
       17                 DR. FROINES:  Yeah.  I don't think I'd
       18   necessarily leap that way.  But one could take this
       19   discussion and write this up in your document and
       20   say -- describe what some of the issues are and
       21   describe what the outcome would be and say this
       22   requires further study or something, further
       23   evaluation.
       24                 DR. GLANTZ:  Well, I think --
       25                 DR. FROINES:  In other words, it's a

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   compromise.  I'm looking for a compromise.
        2                 DR. GLANTZ:  Well, no.  The -- and I
        3   think that's in the document more or less -- maybe
        4   not in exactly those terms, but that's in the
        5   document.  
        6                 It's just -- and I'm not proposing that
        7   we take it out of the document.  I'm happy to leave
        8   it there.  But I think that there is a -- there's --
        9   there are a bunch of important policy issues, in my
       10   view, connected with whether to accept this idea of
       11   the NOAEL which I personally am uncomfortable with. 
       12                 And so I would feel more comfortable,
       13   as I said, if we didn't put them in the findings and
       14   just gave them the NOELs and say that's what we're
       15   finding.  
       16                 If the department, then, as a matter of
       17   policy, wants to use these other numbers, they're in
       18   the report.  The differences, I think, are explained
       19   in the report.  
       20                 And I mean, it may be that we'll, after
       21   the workshop, reach a different comfort level with
       22   this.  But I just -- I think it's giving the
       23   committees this idea of a NOAEL which at least I'm
       24   not comfortable with.  
       25                 Because my whole view of the NOEL is by

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   being cautious and saying no observed effect, you're
        2   saying -- you're kind of building in the fact that
        3   there may be a lot of things going on that you don't
        4   know about.
        5                 DR. FROINES:  But Gary's 100 percent
        6   correct.  Effects occur in physiologic systems that
        7   have no significance whatsoever.  
        8                 DR. GLANTZ:  No, I understand that.  I
        9   understand that.  But also there are things where
       10   you -- where you see small changes that people think
       11   are no big deal that later they decide are a big
       12   deal.  And the -- and especially when you're talking
       13   on a population basis.  
       14                 And so to me the conservative approach
       15   is to say we're going to say where we can't find
       16   anything.  And there may be something we're missing,
       17   but at least everything we've looked at we can't find
       18   anything.  
       19                 And that's a fairly clear endpoint. 
       20   And we're not being forced to make a judgment about
       21   is this change in heart rate or is this change in
       22   blood pressure or is this change in cholinesterase
       23   inhibition of biological importance.  Because I just
       24   feel very uncomfortable making that judgment.
       25                 DR. FROINES:  Well, I would be willing

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   to make -- to go out on a limb on one level.  It
        2   seems to me --
        3                 DR. GLANTZ:  It won't affect the
        4   overall conclusions of the report.
        5                 DR. FROINES:  Somebody's coming in with
        6   a 40 percent inhibition of blood cholinesterase and
        7   one says that's like somebody's blood pressure going
        8   up two points.  
        9                 I'd say he's smoking dope.  Because I
       10   suspect -- significant inhibition of blood
       11   cholinesterase, something else is happening
       12   psychologically that's not good.  
       13                 MR. GOSSELIN:  We discussed at the last
       14   meeting we do as a regulatory threshold require
       15   cholinesterase monitoring of work as using these
       16   compounds and other compounds.  
       17                 And if their cholinesterase is
       18   depressed typically more than 20 percent, it prompts
       19   and sets up a red flag that they're pulled out of
       20   that work environment, and it prompts an
       21   investigation as to what's going on.  So we don't and
       22   we haven't historically dismissed depression of blood
       23   cholinesterase depression as a biomarker.
       24                 DR. GLANTZ:  Yeah.  But, see, I -- I
       25   think that's fine, but I see that as sort of a

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   different question.  And that is a question of like
        2   when you're given the stuff and you're out there in
        3   the regulatory situation having to operationalize
        4   this, you know, you might say, "Well, we're going to
        5   make a -- we're going to do a risk benefit analysis
        6   and be a little bit less cautious than saying no
        7   effect and we'll say it will have a little effect
        8   before we trigger an investigation."  But I see that
        9   as sort of a different -- that's a regulatory
       10   question.
       11                 DR. FROINES:  Paul, what's your NOAEL
       12   based on?  
       13                 MR. GOSSELIN:  Actually, it's written
       14   in here.
       15                 DR. FROINES:  Yeah, I know.  But I'm
       16   not looking --
       17                 MR. GOSSELIN:  It's clinical signs: 
       18   "impaired retinal function, hematological changes,
       19   adverse adrenal changes:  increased weight, fatty
       20   droplets."  
       21                 DR. FROINES:  See, I agree with you,
       22   Stan, to a certain degree.  I think it's fine to
       23   leave the NOAEL in the document, but I think we do
       24   have to differentiate from the fact that those are
       25   not subtle adverse effects.  They're not looking at

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   enzyme inhibitions, for example.  They actually
        2   represent clinical findings.
        3                 So -- and so most of us would argue
        4   that something is probably happening in between
        5   nothing and those adverse effects just listed.  And
        6   it would be nice to know what they were because then
        7   you can be more protective if you could identify
        8   them.
        9                 So I think that having the NOEL values
       10   in is really quite important especially if you define
       11   what the NOEL value is and what the NOAEL values are. 
       12   And hopefully we can improve on that over time.  
       13                 So in some ways I would just like to
       14   make sure everything's out there and clear in our
       15   findings and in the executive summary and then we
       16   don't necessarily have to take out the NOAELs so long
       17   as people know what it is.
       18                 DR. SEIBER:  You said you would add
       19   something, a definition or something, to put it in
       20   perspective.
       21                 DR. FROINES:  I just said they should
       22   put something in that would say that "NOAEL for the
       23   purposes of DEF is blah, blah, blah, blah, blah.  And
       24   the purposes of -- the NOEL for purposes of DEF is
       25   blah, blah, blah, blah, blah."  

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1                 And then you've got -- everybody who
        2   reads it knows what you're talking about.  And the
        3   reader says -- can look at it and say, "Okay.  I
        4   understand that.  I might worry a little bit about
        5   this plasma cholinesterase level as having some
        6   significance and not being benign."
        7                 DR. GLANTZ:  I guess the part about
        8   that -- and again -- the part about that that bothers
        9   me, though, is if I was reading this report as just
       10   sort of a guide or some guy on the street picked it
       11   up and read the findings, that I would take that then
       12   as the SRP saying we think these effects are not
       13   adverse.  And that's the part that bothers me.
       14                 DR. FROINES:  Well, then maybe we need
       15   to put a sentence or two in that -- he needs to put a
       16   sentence or two in that says these -- there may be a
       17   relationship between effects in the central nervous
       18   system where cholinesterase is inhibited that may
       19   mirror these effects and they cannot be considered
       20   without --
       21                 DR. KENNEDY:  To leave it out entirely
       22   you're abrogating your responsibility to recognizing
       23   the limits of your understanding.  I agree totally
       24   with --
       25                 DR. GLANTZ:  Well, I would argue it the

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   other way.  I mean, I think the NOEL is the way to
        2   recognize the limits of your understanding.  Because
        3   I think -- I mean, to go with the NOAEL, I think we
        4   would then want to have a whole big discussion of do
        5   we agree what constitutes an adverse effect. 
        6                 Whereas, if you say no effect, you
        7   can't see anything happen, that's a pretty clearly
        8   defined endpoint.  And I think everybody could agree
        9   that if you can't find any effect, it's unlikely --
       10   you know, then you didn't find any effects.  You
       11   don't have to argue about whether or not it's of any
       12   biological importance.
       13                 Whereas, I think for these other things
       14   we've got to argue about, well, you know, do we agree
       15   with DPR about what constitutes an adverse effect. 
       16   And I'd rather -- and I think if we say, you know,
       17   this is the definition of an adverse effect that's
       18   being used, we're implicitly endorsing that
       19   definition.  And I would just as soon not do that.
       20   But I think that the report -- again, I don't have
       21   any problem with leaving it in the report.  And if we
       22   approve the report, we approve the report.
       23                 MR. FROINES:  I don't agree with you.
       24                 DR. GLANTZ:  Okay.
       25                 DR. FROINES:  I think we do have an

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   obligation to say these are the -- these are the
        2   endpoints that they consider adverse, and we either
        3   should agree with them or not.  And if we don't, we
        4   should say why.  
        5                 I think it's our obligation to accept
        6   theirs or not accept them but give reasons why we do
        7   or don't.  It's all got to be transparent, out on the
        8   table is all I'm saying.  So taking away one-half of
        9   this is, I think --
       10                 But I think we need to make sure of the
       11   definition of the two and then some discussion.
       12                 DR. FRIEDMAN:  With making the point
       13   that there may be some adverse effects at lower
       14   levels in the NOAEL that haven't been detected yet.
       15                 DR. GLANTZ:  How did you guys decide
       16   what constituted an adverse effect?
       17                 MR. GOSSELIN:  In --
       18                 DR. SEIBER:  In experimental animals,
       19   you mean?  
       20                 MR. GOSSELIN:  Yeah.  
       21                 DR. SEIBER:  I thought you just
       22   answered that.
       23                 MR. GOSSELIN:  Yeah.  
       24                 DR. SEIBER:  Didn't you?  
       25                 MR. GOSSELIN:  I mean, it was from the

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   various studies on the acute and subchronic -- and
        2   actually, Gary pointed out what I read to you earlier
        3   was the subchronic signs that were listed in No. 25. 
        4                 Generally what's looked at is all the
        5   studies that are in, trying to look at not just each
        6   one on its own merits but also a pattern that may
        7   develop and looking at whether there's a consistent
        8   pattern over the dosing, whether those -- on one hand
        9   whether those signs continue with increased dosage
       10   you'd expect and whether you start to get into
       11   clinical measurable signs.
       12                 DR. GLANTZ:  Right.  But the question
       13   is how big are they?  You know, like how big an
       14   impaired retinal function are you willing to call not
       15   adverse?  How much hematological change do you call
       16   not adverse, you know?  And what's the justification
       17   for using those values?  
       18                 DR. FROINES:  Well, I think that the
       19   real issues is also that DEF is an adverse effect,
       20   presumably.  But we try and -- if you can, what you
       21   want to do is go away from that extreme to the place
       22   where you think some change is occurring that isn't
       23   just a physiologic homeostasis where you actually are
       24   doing something that moves you out, that affects your
       25   homeostatic patterns.  

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1                 So what you're saying is what is that? 
        2   And we would like that to be relatively early because
        3   presumably if you prevent that, then you prevent
        4   anything else that's going to follow up to death.  
        5                 So the ones he picked are pretty far
        6   along the line.  And the question is what could we
        7   pick that would have a lower -- would be a lower 
        8   adverse effect level.  Would lead measure ALAD
        9   inhibition, for example, as an enzyme inhibition.  So
       10   that's a reversible biochemical process.
       11                 So it seems like the plasma
       12   cholinesterase is in fact a good early adverse effect
       13   that one could use.  It seems to me.  It doesn't mean
       14   it has to be tied -- all the toxicokinetics has to be
       15   tied down, but it's not a benign effect, I think
       16   nobody would argue.  I wouldn't think.
       17                 So anyway, I'm getting into a
       18   subject -- so I think that the discussion we're
       19   having here is what should be in the document so it's
       20   clear to everybody who reads it.  That's all I'm
       21   saying.
       22                 DR. GLANTZ:  Well, no, I don't
       23   disagree.  I mean, I think that's in the document.
       24                 DR. FROINES:  No, in these.
       25                 DR. GLANTZ:  I guess.  But see, then

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   the thing I have if you take all these different
        2   signs and things that they're measuring, I think we
        3   would need to spell out what exactly is the threshold
        4   for calling each one of these things adverse, which
        5   I'm pretty sure is in the document.  
        6                 MR. GOSSELIN:  Yeah.  In the document
        7   it talks about the number of species -- the number of
        8   the animals that were tested, the number that were
        9   positive.  And so each one of those things were
       10   specifically described in --
       11                 DR. GLANTZ:  Right.  But see, then --
       12   but the question -- and I mean, I seem to not be in
       13   the majority to be worried about this.  But the
       14   problem is I think I'm just concerned about us
       15   saying, "Okay.  We accept those definitions of where
       16   you get the number that you should consider of
       17   concern" without, you know, a debate about, "Okay. 
       18   Well, how much of a change in retinal function would
       19   we call 'adverse'?"
       20                 Do you understand what's concerning me? 
       21   And I think the way to punt on this, I mean, is to
       22   leave it in the document just the first time out --
       23   it's fairly well explained in the document -- but to
       24   not endorse the idea of the no observed effect level
       25   quite yet.  

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1                 If this is going to be something that's
        2   going to come up in this workshop we're going to have
        3   in a couple of months, maybe after that then I would
        4   be more comfortable with doing it.  
        5                 But I think that there's actually a big
        6   policy decision about whether you should use NOELs or
        7   NOAELs, and I'm uncomfortable with it, you know.  And
        8   I think to put them in the findings is for us to
        9   basically be endorsing that approach and those -- and
       10   those -- those definitions of what's adverse.
       11                 DR. SEIBER:  See, I don't feel as a
       12   panelist that I'm endorsing that by putting that in
       13   there particularly if we define.  I think if we set
       14   out what's known about this chemical at this point in
       15   time, I don't feel that I'm endorsing a position.
       16                 DR. GLANTZ:  But the adverse -- well,
       17   no.  But what you're doing is you're endorsing your
       18   position to what constitutes "adverse effect."  And
       19   we haven't really gone -- except for the
       20   cholinesterase inhibition, we haven't had a big
       21   discussion of constitutes and adverse effect on every
       22   single one of these endpoints, and that's a big long
       23   discussion.  And I don't think -- I think -- I'm just
       24   uncomfortable sort of de facto accepting that. 
       25                 Again, I'm not saying they should take

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   it out of the document.  I think the document
        2   explains what they mean, and people can read that and
        3   make their own judgment about whether or not they
        4   consider that an acceptable procedure from a
        5   regulatory point of view.  
        6                 DR. FROINES:  Well, I think that what
        7   you just said is a very good point in a sense. 
        8   Because our history -- our history has been always
        9   based on a dichotomous endpoint.  Right?  You either
       10   have cancer or you don't.  And that's the way we
       11   viewed the world.  
       12                 We did some stuff with lead.  Now,
       13   lead -- you know, all of a sudden you've got -- it's
       14   pretty easy with lead because we got a national
       15   academy of science and CDC and all these other people
       16   come in and say, "Well, we want to keep everybody
       17   below 10, and we want to keep everybody below 20." 
       18   And so we don't have to go into all the subtleties of
       19   dealing with continuous variables around effects.
       20                 Now, here -- and this is where the
       21   rubber is about to start to meet the road, because
       22   now we have to take into account issues of severity
       23   and issues of distribution, don't we?  
       24                 How many animals -- and we have to take
       25   into account individual susceptibility because you

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   may have some animals that show some effects and
        2   others don't.  
        3                 And if you take the mean of that, you
        4   may have some results.  But if you look at the
        5   individual variability, you may want to say that
        6   these animals do have an effect.  
        7                 So you have interindividual
        8   variability, you have the severity issue, and you
        9   have distributional issues in general.  We haven't
       10   dealt with any of that, and it's obviously quite
       11   complicated.  
       12                 I mean, how much respiratory irritation
       13   from formaldehyde do you have to have at one-tenth of
       14   a part per million before you say that that's too
       15   much.
       16                 Those are the kind of issues why people
       17   haven't dealt effectively with non-carcinogens. 
       18   Carcinogens at some level are easy because they're
       19   dichotomous.  Not really when you get into mechanism,
       20   but that's the way you do it.   
       21                 So I think that we have to do exactly
       22   what you said.  I think we have to take up this issue
       23   of non-cancer endpoints and how we're going to define
       24   what do we take -- what do we mean by "severity," you
       25   know.  What's -- how many animals have to have these

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   effects and so on and so forth.  
        2                 All of these are complicated questions. 
        3   And they're dealt with awfully simplistically by and
        4   large by most people.  And so my sense is that what
        5   we have to do is come up with something that gets us
        6   through this document --
        7                 DR. GLANTZ:  Right.  
        8                 DR. FROINES:  -- and then try and
        9   address what are obviously difficult questions in
       10   another forum.  Otherwise we'll sit here and talk
       11   about them.  And most of the issues we'd like to talk
       12   about we don't even know what we're talking about. 
       13   And there is something to be said for knowing about
       14   what you're talking about.
       15                 DR. GLANTZ:  And see, that's why what
       16   I'm proposing to do.  To get this document finished,
       17   okay, is to simply leave this -- leave the NOAELs in
       18   the document but leave them out of our findings and
       19   then it may be that after we have this workshop and
       20   figure more of this out, maybe we would want to go
       21   back and re-add them.  
       22                 But I just think there's a whole lot of
       23   stuff implicit in these NOAELs that I'm uncomfortable
       24   with, and I don't see where it would hurt anything to
       25   take them out of the findings.

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1                 DR. FROINES:  As the chair's
        2   prerogative, I'm going to take a vote.  And I'm --
        3                 DR. GLANTZ:  I'll probably lose.
        4                 DR. FROINES:  -- going to make a
        5   motion -- or somebody has to make a motion.  I'm
        6   going to say -- make a motion that says we leave the
        7   NOELs in -- with the NOELs in our findings. 
        8                 DR. GLANTZ:  I'll move that.
        9                 DR. FROINES:  So now we moved that so
       10   we can move on.
       11                 DR. FUCALORO:  I second for the purpose
       12   of -- 
       13                 DR. FROINES:  The NOELS and NOAELs.  
       14                 DR. GLANTZ:  What he's moved is the
       15   NOAELs be left in the findings.
       16                 DR. FROINES:  My motion was essentially
       17   the status quo with further explanation.
       18                 DR. FRIEDMAN:  Right, with explanation.
       19                 DR. SEIBER:  And you second it?  
       20                 DR. GLANTZ:  I seconded it, for the
       21   purposes --
       22                 DR. FUCALORO:  Well, he made the
       23   motion, and I seconded it.
       24                 DR. GLANTZ:  I made the motion, and he
       25   seconded it.  

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1                 DR. FROINES:  He's just showing that
        2   he's friendly to the motion he's about to lose.  So
        3   all in favor of that motion raise your hand.
        4                 And Peter would have voted our way too.
        5                 DR. GLANTZ:  Don't I at least get to
        6   vote no for the record?  
        7                 DR. FROINES:  How many oppose it?  
        8                 DR. GLANTZ:  I oppose it.
        9                 DR. FUCALORO:  How many extensions?
       10                 DR. GLANTZ:  But if Byus had been here,
       11   I would have won.  
       12                 DR. FROINES:  Can we move on then? 
       13   We're trying to finish this.  
       14                 DR. FUCALORO:  I don't think so.
       15                 DR. GLANTZ:  Well, I could dream.
       16                 DR. FROINES:  What time is it?  
       17                 DR. FRIEDMAN:  20 to 1:00.
       18                 DR. SEIBER:  John, where did we come
       19   out with that last statement in the findings about
       20   whether we recommend the DPR director take this under
       21   to the next step or whether we in fact come out and
       22   recommend --
       23                 DR. FROINES:  We hadn't finalized it. 
       24   We had basically -- I think let's leave that for
       25   last.  

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1                 But are there any other technical
        2   issues within the findings that anybody wants to
        3   comment on?  Let's do the science before we do the
        4   politics.
        5                 DR. SEIBER:  I've got a few.
        6                 DR. FROINES:  Your vote won.
        7                 DR. KENNEDY:  I'm glad I wasn't here.
        8                 DR. GLANTZ:  For the record, he should
        9   vote just to -- right?  No?  He doesn't have to? 
       10   Okay.
       11                 DR. KENNEDY:  I vote to leave it in.
       12                 DR. GLANTZ:  Okay.  We're all wrong.
       13                 DR. SEIBER:  In the bulk of the
       14   findings, again, I went through it and made some
       15   cross-outs and changes like that which I'll be happy
       16   to give to Peter or to you or to Paul.  
       17                 What should I do?  
       18                 DR. FROINES:  Give it to Peter, and he
       19   can be our person.
       20                 DR. GLANTZ:  Do you mean additional
       21   changes beyond the ones on this fax that we got?  
       22                 DR. SEIBER:  Right.  Well, they're not
       23   additional.  They're things that either were
       24   misspelled or --
       25                 DR. GLANTZ:  But it's nothing

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   substantive?
        2                 DR. SEIBER:  No, no, not substantive.
        3                 DR. FRIEDMAN:  But there's something
        4   you said needs clarification.
        5                 DR. SEIBER:  Well, I have subsequently
        6   read it over, and I guess personally I'm happy.  I
        7   didn't make any changes on those things.
        8                 DR. FROINES:  It does mean, by the way,
        9   on this vote, that you need to put a value in for the
       10   MOE based on the NOEL.
       11                 MR. GOSSELIN:  I think that was in
       12   there.
       13                 DR. FROINES:  If it isn't --
       14                 MR. GOSSELIN:  We did add those in.
       15                 DR. FROINES:  Okay.  Good.  So you're
       16   okay.
       17                 DR. SEIBER:  Yeah, I'm okay.
       18                 DR. FROINES:  Tony's okay.  You're
       19   okay.  So there are no more technical comments on the
       20   findings.
       21                 DR. GLANTZ:  I guess there's one thing
       22   that I think before we vote on them, maybe at lunch
       23   maybe Paul and the others can go write up the
       24   definition of the NOEL versus NOAEL that we're going
       25   to incorporate into the findings so we can consider

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   that.
        2                 MR. GOSSELIN:  I did have one question
        3   because I just wanted to clarify.  Did you want it
        4   just specifically stated that the report identified 
        5   a NOAEL for the purposes of DPR to consider in risk
        6   mitigation or risk management?  
        7                 DR. FROINES:  Well, that's fine.  But I
        8   also want you to say what the NOAEL is.  What are the
        9   endpoints you're considering.
       10                 MR. GOSSELIN:  That's in here.
       11                 DR. GLANTZ:  In the findings?  
       12                 MR. GOSSELIN:  Yeah.
       13                 DR. FRIEDMAN:  We should have our
       14   caveat what we want to say in terms of the fact that
       15   there may be adverse effects between the NOAEL and
       16   NOEL that have not been detected.
       17                 MR. GOSSELIN:  If you wanted the
       18   specifics about the NOEL indicating the
       19   cholinesterase suppression in the plasma, that's in
       20   there.  And in the clinical science, the specific
       21   clinical science for the NOAEL, those are in there.
       22                 DR. FUCALORO:  No. 18.
       23                 MR. GOSSELIN:  No. 18 for acute and
       24   No. 25 for the subchronic.
       25                 DR. FROINES:  We have to stop for lunch

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   but -- well, let's look at these and see what we need
        2   to do to meet that one.  
        3                 DR. GLANTZ:  I mean, I would actually
        4   be happier if we took out the sentence about risk
        5   management.  I'm just uncomfortable saying basically
        6   what we're doing is agreeing that this is the number
        7   they should use for risk management.  And I don't
        8   agree with that, necessarily.  So maybe we can --
        9   it's at the bottom of page 3.  Take the last sentence
       10   on page 3 out.
       11                 DR. FUCALORO:  It's in item 18.  
       12                 DR. GLANTZ:  Yeah.  
       13                 DR. FUCALORO:  And when I pointed it
       14   out earlier, which said --
       15                 DR. GLANTZ:  Maybe I can win.
       16                 DR. FUCALORO:  -- assuming a 24-hour --
       17   well, it's the sentence prior to that.  I'm wrong.
       18                 DR. GLANTZ:  It says, 
       19                    "Since the report will also
       20           provide the basis for risk
       21           management, NOAEL provides the
       22           information required for risk
       23           management."
       24                 DR. FRIEDMAN:  We're not looking at the
       25   same thing at the bottom of page 3.

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1                 DR. GLANTZ:  Okay.  It's No. 18.
        2                 MR. FROINES:  Mine doesn't have that.
        3                 DR. FUCALORO:  It disappeared in this
        4   copy.
        5                 DR. KENNEDY:  The one that Dr. Seiber
        6   corrected doesn't have that statement in it.
        7                 MR. GOSSELIN:  Because prior to making
        8   the corrections of Dr. Seiber's, Bill had sent over
        9   some comments and thoughts about wanting to define
       10   what the NOEL versus the NOAEL.  So --
       11                 DR. GLANTZ:  Well, if we're working off
       12   of Seiber's edited version, then there's nothing to
       13   discuss.
       14                 DR. KENNEDY:  It's a non-issue.  I tend
       15   to agree with it.  I think it's fine as it is here.
       16                 DR. GLANTZ:  In Seiber's, you mean?  
       17                 DR. KENNEDY:  Yeah.  
       18                 DR. GLANTZ:  Okay.  
       19                 DR. FROINES:  In fact, in Seiber's it
       20   doesn't exist.
       21                 DR. FUCALORO:  It's eliminated, right.
       22                 DR. GLANTZ:  That's fine.  Nevermind.  
       23                 DR. FROINES:  Well, then let's take a
       24   break and come back.  And the only thing we have left
       25   to do is the policy question which we've more or less

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   resolved right now.  
        2                 Am I missing something?  
        3                 DR. GLANTZ:  We do need to know that
        4   one extra sentence, and somebody needs to write that
        5   about something could be happening between --
        6                 DR. FRIEDMAN:  Could you write that
        7   sentence?  
        8                 DR. GLANTZ:  Well, you thought of it. 
        9   You write it.  
       10                 DR. FRIEDMAN:  Okay.  I'll write it. 
       11   Where does it go?  
       12                 DR. GLANTZ:  In number --
       13                 DR. FROINES:  Why don't you sit with
       14   George and his folks or Paul or whoever, somebody
       15   from the staff to --
       16                 DR. FRIEDMAN:  I need to eat first.
       17                 DR. FROINES:  We'll reconvene at 1:15,
       18   a half hour lunch.  
       19                 (Lunch recess.) 
       20                 DR. FRIEDMAN:  I would suggest we
       21   insert this sentence to satisfy people's concerns: 
       22   "It should be recognized that NOAELs are based on
       23   limited existing knowledge and that adverse effects
       24   not yet measured may occur at lower levels of
       25   exposures."  

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1                 And Peter suggested that we could even
        2   make that stronger by saying, "It is important to
        3   note" rather than "It should be recognized."  That
        4   could go with either one.  
        5                 So I propose that we insert that.  I'm
        6   not sure of the exact spot.  People were saying in
        7   item 18.
        8                 DR. GLANTZ:  I move we insert that
        9   sentence in item 18 with Peter's wording.
       10                 DR. SEIBER:  Second.
       11                 DR. FROINES:  All opposed?  So it's
       12   unanimous.
       13                 Are we ready to go?  Bill?
       14                 MR. LOCKETT:  Yeah.
       15                 DR. FROINES:  We have to make one final
       16   decision, I think, and that is are we comfortable
       17   with section 34 in the way it's stated?
       18                 DR. GLANTZ:  No.
       19                 DR. SEIBER:  John, I'd like to ask a
       20   question, and it's strictly out of ignorance.  This
       21   is the first pesticide, I think, that we're doing
       22   this for, and I'd just like to know what we're
       23   required to do and what this action triggers in terms
       24   of follow-up.  
       25                 Because it's quite different.  With ARB

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   we make the recommendation, and then they have a
        2   meeting and consider it further, and they may or may
        3   not agree with us.  
        4                 But in this case it's the director of
        5   DPR.  I think we go mainstream to the director, as I
        6   understand it.  Can somebody explain this a little
        7   bit better?  
        8                 MR. GOSSELIN:  Actually, it says, and
        9   this is from the statute, 
       10                    "Within ten working days
       11           following receipt of the findings of
       12           the scientific review panel pursuant
       13           to subdivision B, the director shall
       14           prepare a hearing notice and proposed
       15           regulation which shall include the
       16           proposed determination as to whether
       17           a pesticide is a toxic air
       18           contaminant."
       19                 DR. FROINES:  And he holds a hearing?
       20                 MR. GOSSELIN:  That I will have to go
       21   back and check.  But I would read that once you
       22   prepare findings and say "This document has all the
       23   information" and with your findings and submit that,
       24   we have ten working days to get a package together
       25   and to propose -- to either agree to list or not list

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   but at least hold a hearing or propose a regulation
        2   package.
        3                 DR. GLANTZ:  Well, how about -- this is
        4   not the way we've worded this conclusion in the past. 
        5   Does anybody have any of the other reports we've
        6   done?  
        7                 MR. GOSSELIN:  I took this from either
        8   lead or diesel.
        9                 DR. GLANTZ:  Oh, really?
       10                 MR. GOSSELIN:  Yeah.
       11                 DR. GLANTZ:  And so it said the same --
       12   "We recommended that the ARB initiate regulatory
       13   steps"?  I just recall it just saying that "For these
       14   reasons the SRP recommends identification as a toxic
       15   air contaminant."
       16                 MR. GOSSELIN:  That's different.  I
       17   wanted to cite this section, specifically, and that's
       18   the section I read is 14023D.  So what it's saying is
       19   to initiate the steps under that section.
       20                 DR. FROINES:  We could -- we could say
       21   "For these reasons we agree with the science
       22   presented in the report and recommend -- and based on
       23   those scientific findings consider DEF a toxic air
       24   contaminant.  We recommend that the director of DPR
       25   initiate regulatory steps to list it."

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1                 DR. GLANTZ:  Okay.
        2                 DR. FROINES:  So in other words, we
        3   conclude that it's a toxic air contaminant and then
        4   we recommend.
        5                 DR. GLANTZ:  Okay.  I'm happy with
        6   that.
        7                 DR. FROINES:  That's what we've done in
        8   the past.
        9                 DR. FRIEDMAN:  Yeah, that would be
       10   better.
       11                 DR. GLANTZ:  Okay.  Is that okay with
       12   you?  Okay.  I so move.
       13                 DR. FRIEDMAN:  Second.
       14                 DR. GLANTZ:  I want to win one.
       15                 DR. FUCALORO:  You've won one already.
       16                 DR. GLANTZ:  Oh, I did?  
       17                 DR. FUCALORO:  You're winning all of
       18   them, for crying out loud.  
       19                 DR. GLANTZ:  I lost the last one.  
       20                 DR. FROINES:  No, you won the vote. 
       21   You simply lost the principle.
       22                 DR. GLANTZ:  That's true.  Actually, it
       23   was my motion, wasn't it?
       24                 DR. FROINES:  All in favor of that?
       25                 DR. FRIEDMAN:  I am.

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1                 DR. BYUS:  What was that?  I missed it. 
        2   I'm sorry.
        3                 DR. FROINES:  You know, we're all the
        4   same.  We're getting older, and you're not supposed
        5   to ask people to repeat what they said.  You say "For
        6   these reasons we agree with the science presented in
        7   the report and based on the science" -- 
        8                 DR. FUCALORO:  The scientific findings.
        9                 DR. FROINES:  -- "the scientific
       10   findings consider -- have included DEF as a toxic air
       11   contaminant.  We further recommend that the blah,
       12   blah, blah."  Now she knows it twice, and we're saved
       13   from our Alzheimer's.
       14                 DR. GLANTZ:  Just for Dr. Byus, we had
       15   a big -- I had proposed removing the NOAEL from the
       16   findings for reasons that were discussed endlessly. 
       17                 Dr. Froines made a suggestion we make a
       18   motion to keep them as a courtesy.  I made the motion
       19   and then lost.  But as he pointed out, I actually won
       20   because my motion passed with me voting no.  I'm
       21   ready for Congress.
       22                 DR. FROINES:  This is a very collegial
       23   group today.
       24                 Paul, it's -- it's just great working
       25   with you on all of this.  In the '80s it wasn't so

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   much fun.  Stan and I remember.  And this general
        2   spirit, I think, is terrific.                 I think
        3   we're really on the way on this.  And I think this is
        4   a good first step.  It's good just after the election
        5   to bring back a positive outcome.  It's good.
        6                 MR. GOSSELIN:  Thank you.  And I think
        7   the staff that worked on this put a lot of effort to
        8   be responsive and put all the -- lay the science into
        9   it.
       10                 DR. FROINES:  Shall we move on to
       11   parathion?  
       12                 DR. GLANTZ:  Can I move that we accept
       13   the report as amended by the discussion and the
       14   finding -- or we've already accepted the findings. 
       15                 DR. FROINES:  Yeah, I guess you're
       16   right.  
       17                 DR. GLANTZ:  We didn't accept the
       18   report.  
       19                 Huh?  
       20                 DR. FROINES:  I always forget that --
       21                 DR. GLANTZ:  I'd like to move that we
       22   accept the report with the appropriate changes that
       23   were discussed today.
       24                 DR. SEIBER:  Second.
       25                 DR. FROINES:  All of in favor?  

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1                 This is a landmark decision, isn't it? 
        2   This is our first in the history of this program. 
        3   Did we vote once before?  Was there a formal vote
        4   before?  
        5                 UNIDENTIFIED SPEAKER:  Ethyl parathion.  
        6                 DR. ALEXEEFF:  Ethyl parathion.
        7                 MR. GOSSELIN:  Eleven years ago.
        8                 DR. FROINES:  Eleven years ago.  
        9                 DR. GLANTZ:  But that was to turn it
       10   down, wasn't it?  
       11                 DR. FROINES:  It's still a historic
       12   event.  
       13                 Let's move on.  I'm sure we can find
       14   something to disagree about.
       15                 MR. GOSSELIN:  Thank you.
       16                 We're going to methyl parathion?
       17                 DR. FROINES:  I think what we're going
       18   to do, Paul, is what we'd like you to do is
       19   essentially make a presentation that you were
       20   thinking of making, and then we'll probably stop and
       21   then take up the actual discussion at the next
       22   meeting.  Because you're going to have more material
       23   and more comments -- I think Ruby said that there was
       24   more coming.  
       25                 DR. REED:  Yes.  Correct.

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1                 MR. GOSSELIN:  And I should preface
        2   that we did have the comment period that closed at
        3   the end of October.  We had a workshop.  And I
        4   apologize for not making arrangements for members to
        5   be there, and we'll fix that in the future.
        6                 We didn't have a large number of
        7   comments, but we did receive one significant set of
        8   comments, and it was a stack of four new studies that
        9   the representatives from the registrar submitted.
       10                 Those studies right now are in the
       11   process of going through -- the first step is data
       12   review which is to determine whether those studies
       13   were complete and adequate, and it will go to the
       14   group to characterize that.  And we've kind of put
       15   that on a fast track.
       16                 We're going -- taking those -- those
       17   new data as comments, so we're largely holding that
       18   the report itself is going to remain intact.  Once we
       19   complete the review of those studies, we're going to
       20   report back in an addendum fashion to the report
       21   because we figured there are going to be, as we go
       22   through discussions, some changes to the report and
       23   reflect how those new data either change or don't
       24   change the assessment of methyl parathion.
       25                 The one other issue that was raised is

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   the changing -- and this is going to be the changing
        2   use patent of methyl parathion, which is going to be
        3   more typical of pesticide use versus what we saw with
        4   DEF where methyl parathion has a variety of uses and
        5   a variety of crops and we've seen some of the
        6   counties and some of the cropping patents over the
        7   past ten years change in the use patent.  And that's
        8   going to be sort of a dilemma we're going to have to
        9   appreciate as we go through evaluating pesticides. 
       10                 With that I'll have the first
       11   presentation which will be Kevin Kelley on
       12   environmental fate.  
       13                 (Off the record.) 
       14                 MR. KELLEY:  Okay.  I guess we're ready
       15   to get started here.  My name is Kevin Kelley.  I'm
       16   an associate environmental research scientist for the
       17   Department of Pesticide Regulation.  I'm the author
       18   of the part A of "Evaluation of Methyl Parathion as a
       19   Toxic Air Contaminant" document.  
       20                 The overheads that I present today, you
       21   all should have a copy of it.  Peter passed them out. 
       22   So if you can't see something up on the overheads
       23   there, you'll have a copy of it.
       24                 This afternoon I'm going to talk about
       25   the physical and chemical aspects of methyl

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   parathion, the use of methyl parathion in California
        2   including the crops on which it's used and the
        3   counties in which it's used, then I'll move on to the
        4   environmental fate of methyl parathion, and then
        5   concentrations of methyl parathion in the air.
        6                 Next.
        7                 Okay.  Since nobody can see this, I
        8   guess you'll just have to look off your handouts.
        9                 DR. GLANTZ:  Why don't you move the
       10   projector further back.  It's too faint.  
       11                 MR. KELLEY:  Methyl parathion is an
       12   insecticide-acaricide registered for use in
       13   California to control insect, mite, and other
       14   arthropod pests in cropland situations.  
       15                 Methyl parathion is a molecular formula
       16   of C8 H10 NO5 PS and has a molecular weight of
       17   263.21.  At room temperature methyl parathion is in
       18   the form of colorless crystals which emit a faint,
       19   garlic-like odor.  
       20                 Methyl parathion melts at approximately
       21   35 degrees Celsius and has a boiling point of
       22   approximately 119 degrees Celsius at 0.13 millibar.  
       23                 Methyl parathion has a vapor pressure
       24   of 2.3 millipascals at 25 degrees C and a Henry's Law
       25   Constant of 10.3 times 10 to the minus 8th meters

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   cubed times atmospheres per mole.  Specific gravity
        2   is 1.3858.
        3                 Methyl parathion is sparingly soluble
        4   in water at 12.9 milligrams per liter at 20 degrees
        5   Celsius.  It is slightly soluble in petroleum
        6   distillates and readily soluble in most organic
        7   solvents.  In alkaline or acidic media methyl
        8   parathion rapidly hydrolyzes.  
        9                 Next.
       10                 Methyl parathion is used to control
       11   insects and other invertebrate pests in more than 35
       12   crops grown in California.  It's also used to control
       13   insect pests in and around nurseries and nursery
       14   plantings, for public health control, for regulatory
       15   pest control, and free landscape maintenance.  
       16                 Methyl parathion controls lepidopterous
       17   pests of alfalfa, almond, apricot, peach, and other
       18   stone fruits.  Methyl parathion is used extensively
       19   in rice cultivation for the control of tadpole shrimp
       20   and labeled for the use against the rice leafminer. 
       21                 It is also used for the control of
       22   aphids, grasshoppers, leafminers, scale, spider
       23   mites, and other pests, and for the control of
       24   mosquitoes in irrigated pastures.
       25                 Next.

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1                 This is a historical use of methyl
        2   parathion which is shown from 1977, right here
        3   (indicating), to 1995 at the left end or right end
        4   over here.
        5                 DR. GLANTZ:  How come the use fell off
        6   so suddenly there?  
        7                 MR. KELLEY:  Before 1977 we don't have
        8   a lot of use reports, but for several years back it
        9   was used in over a million pounds per acre, and then
       10   in 1978 it just dropped down to about 260,000.  And
       11   basically there was less used in most of the crops it
       12   was used on.
       13                 DR. GLANTZ:  Do you know why?  
       14                 MR. KELLEY:  No.  I haven't been able
       15   to figure that out yet.
       16                 DR. SEIBER:  Probably -- it could have
       17   been new alternatives were brought in like
       18   chlorpyrifos and some of the other newer
       19   organophosphates.  That's just a guess.  
       20                 MR. KELLEY:  Yeah, it didn't seem to be
       21   a change in the commodities that it was used on, so
       22   there wasn't some crop that just it stopped
       23   completely on.  
       24                 The high, as I said was 20 years ago,
       25   was over one million pounds in 1977, and the lowest

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   used in the last 20 years was right here in 1991 of
        2   72,000 pounds (indicating).  And since 1991 uses
        3   increased slightly to approximately 153,000 pounds in
        4   1995.                
        5                 The average use for -- the average
        6   value -- excuse me.  The average use of methyl
        7   parathion in the last ten years is approximately
        8   140,000 pounds per year.
        9                 Next.
       10                 Seven crops account for 73 percent of
       11   methyl parathion applied from 1990 through 1995. 
       12   These crops are alfalfa, apple, grapes, nectarine,
       13   peach, plum, and finally rice.
       14                 Next.
       15                 Methyl parathion is also applied to 28
       16   minor use crops.  Applications to these crops account
       17   for approximately 27 percent of the remaining average
       18   methyl parathion used from 1990 through '95. 
       19                 Applications to -- of methyl parathion
       20   to such crops as small grains and onions average over
       21   3,000 pounds a year, whereas, applications to cotton,
       22   lettuce, pears, sugar beets, and tomatoes average
       23   between 1,400 and 2,000 pounds.  And finally,
       24   applications to remaining crops average from 40
       25   pounds per year to 900 pounds.

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1                 DR. GLANTZ:  What is "AI"?  
        2                 MR. KELLEY:  Active ingredient.  Sorry.
        3                 Next.
        4                 Methyl parathion applications to most
        5   of the major crops has shifted over the last ten
        6   years.  Applications to rice for approximately 55,000
        7   pounds -- which is the black bar right here
        8   (indicating) -- in 1990 and it's decreased to 31,000
        9   pounds in 1995.  
       10                 The reported amount of methyl parathion
       11   applied to rice in 1993 was over 500,000 pounds
       12   although according to the use report shows that
       13   there's probably a 10,000-pound excessive just due to
       14   calculation errors in the use report.  As you can see
       15   also, applications to grape, peaches, nectarines, and
       16   plums have greatly increased since 1990.
       17                 Next.
       18                 DR. BYUS:  Do you think that trend's
       19   going to continue?  Or I mean, is that --
       20                 MR. KELLEY:  Boy, I'd like to see the
       21   1996 use report.  I really would.  Because you
       22   know -- that's what this graph right here is
       23   basically about.  
       24                 As you can see in the straight line
       25   here (indicating), this is use in rice.  Use in rice

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   from 1996 to '89 averaged approximately 900,000 --
        2   90,000 pounds per year.  
        3                 And in 19 -- 1988 there was a big
        4   decrease that started in rice, and it went all the
        5   way through until 1991 where use was at the lowest,
        6   which is approximately 24, 25,000 pounds of rice. 
        7   And that's crept back up slightly to 31,000 pounds in
        8   '95.  
        9                 And since 1990 use on stone fruits,
       10   which is the dotted line through here, this is where
       11   it started to increase in stone fruits.  And I
       12   grouped all the stone fruits together because they're
       13   generally grown in the similar areas and more or less
       14   typed intercropped so that you -- it just made sense
       15   to put them together.
       16                 DR. GLANTZ:  What are stone fruits? 
       17                 MR. KELLEY:  Peaches, nectarines,
       18   plums; fruits with pits -- apricots.  
       19                 And since 1990 use in stone fruits has
       20   increased to 64,000 pounds in '93, 67,000 pounds in
       21   '94, and 62,000 pounds in 1995.  
       22                 And I also have grapes listed on this,
       23   which is the very faint line with the triangles.  And
       24   use on grapes has risen from approximately 2,500
       25   pounds in 1992 to over 21,000 pounds in 1995.

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1                 Next.
        2                 And historically 42 counties in
        3   California report a methyl parathion use from 1990 to
        4   1995.  Of these, eight counties accounted for 65
        5   percent of the total use, and these counties are
        6   Colusa, Fresno, Kern, Riverside, San Joaquin, Sutter,
        7   Tulare, and Yuba Counties.
        8                 Next.
        9                 And in these counties application --
       10   excuse me, the amount of methyl parathion is applied
       11   that's shifted and reflects basically the change in
       12   pest control use patterns and the change in the
       13   applications to the commodities grown within those
       14   counties.
       15                 Applications to Colusa County have
       16   decreased from 27,000 pounds to 4,600 pounds;
       17   whereas, applications in Fresno County have risen
       18   from 1,100 pounds in 1990 to 34,000 pounds in 1995.
       19                 Next.
       20                 And this next graph is just a graph of
       21   counties -- the other counties of which methyl
       22   parathion is applied.
       23                 Next.
       24                 What are the sources of methyl
       25   parathion and methyl parathion and methyl paraoxon in

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   the environment?  The sole source of methyl parathion 
        2   in the environment derives from its application and
        3   use as a pesticide.  
        4                 And since methyl paraoxon is a
        5   breakdown product of methyl parathion, its sole
        6   source in the environment comes from the use of
        7   methyl parathion also.  
        8                 As of September 1998 nine methyl
        9   parathion containing products are currently
       10   registered for use in California.  Formulations of
       11   methyl parathion include seven emulsifiable
       12   concentrate products, one microencapsulated product,
       13   and one emulsifiable concentrate mixture with 
       14   thiodan.  
       15                 This graph shows a historical peak
       16   using data from 1990 through to 1995, and it shows
       17   that there's a seasonal peak for methyl parathion
       18   used which occurs in May for these years.  
       19                 This peak corresponds to its use in two
       20   separate locales.  The first locale is the
       21   rice-growing regions in Sutter, Colusa, Tulare
       22   Counties where applications begin in early May and
       23   continue through early June, a four- to six-week
       24   period.
       25                 The second locale is the alfalfa and

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   stone fruit growing regions in Fresno and San Joaquin
        2   Counties where applications again begin in mid-May
        3   and continued for eight to twelve weeks.
        4                 For most of the cropland situations
        5   methyl parathion applications are made on an
        6   as-needed basis for the control of damaging insect
        7   populations.  The fewest methyl parathion
        8   applications occur in between November -- right there
        9   (indicating) -- December, January, and February of
       10   each year.
       11                 Next.
       12                 This is a yearly breakout of the
       13   previous graph and again just shows that through the
       14   time the applications tend to remain concentrated in
       15   May and June with April and July as secondary high
       16   use months.
       17                 Next.
       18                 What is the fate of methyl parathion in
       19   the environment?  In the environment methyl parathion
       20   is graded by one of three major chemical or
       21   microbial -- and microbial pathways.  
       22                 The first involves the production of
       23   methyl paraoxon.  It's right here (indicating). 
       24   Reaction:  hydrolytic in soil and water and
       25   photolytic in air.  

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1                 The second pathway -- this goes from
        2   methyl parathion this way -- is also hydrolytic in
        3   air and water and in soil and plants.  Methyl
        4   parathion is cleaved producing para-nitrophenol and
        5   dimethyl phosphorothioic acid.  
        6                 The third reaction is from methyl
        7   parathion to methyl aminoparathion, and this reaction
        8   involves reduction of the nitro group, and this
        9   reaction occurs in flooded soils, soils high in
       10   organic matter, and soils with strong reducing
       11   conditions.  Methyl aminoparathion is then further
       12   degraded to para-aminophenol and dimethyl
       13   phosphorothioic acid.  
       14                 In air methyl paraoxon is considered
       15   relatively resistant to further degradation.  In soil
       16   and water methyl paraoxon may be converted to
       17   para-nitrophenol and dimethyl phosphoric acid.  And
       18   if conditions favor reduction, methyl paraoxon will
       19   be converted to para-aminophenol and dimethyl
       20   phosphoric acid.  
       21                 The final fate of these degradative
       22   products should be complete mineralization to CO2,
       23   H20, oxygen, and phosphorus and sulfur compounds.
       24                 Recent information received by DPR
       25   indicates that under laboratory conditions the half

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   life of methyl parathion in air may be as low as
        2   30 minutes.  
        3                 Other data indicates that in more real
        4   conditions the half life would be approximately 13
        5   hours with methyl parathion's completed lifetime may
        6   be as short as 18 hours.
        7                 The information also indicates that
        8   another compound, 2-methyl-4-nitrophenol, was
        9   produced and intimates that many other breakdown
       10   products should be produced and immediately washed
       11   from air. 
       12                 Next.  If you could rotate that,
       13   slightly.  Thank you.  
       14                 What are the concentrations of methyl
       15   parathion reported in the literature?  Airborne
       16   concentrations of methyl parathion in the literature
       17   range from .4 to 688.2 parts per trillion.
       18   Formulation and sampler placement have major effects
       19   on measured concentrations.  
       20                 Jackson and Lewis in 1979 did a study
       21   measuring one -- taking one- to two-hour samples at
       22   the end of tobacco rows in North Carolina after
       23   applications of methyl parathion.  
       24                 Methyl parathion was applied in
       25   approximately one pound per acre in both situations,

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   and there were two formulations that were used:  one
        2   was the emulsifiable concentrate; the second was a
        3   microencapsulated formulation.  
        4                 And this graph shows that immediately
        5   following application for the emulsifiable
        6   concentrate formulation, methyl parathion
        7   concentrations were 688 parts per trillion; whereas,
        8   for the microencapsulated formulation the
        9   concentrations were 353 parts per trillion.  
       10                 DR. SEIBER:  Kevin, do you know offhand
       11   in California is it microencapsulated or the
       12   emulsifiable concentrate the more relevant formula? 
       13                 MR. KELLEY:  If you're talking about
       14   the rice, it would be the emulsifiable concentrate. 
       15   I didn't get a chance to look at the data in the last
       16   two weeks, but I'm trying to find out, especially in
       17   stone fruits, if they're going to be using the
       18   microencapsulated formulation or if they're using the
       19   emulsifiable concentrate.
       20                 DR. SEIBER:  Because there's quite a
       21   difference here.
       22                 MR. KELLEY:  Right.  
       23                 DR. SEIBER:  Yeah.  
       24                 DR. FUCALORO:  And they assume that to
       25   be real.  In other words, you mentioned that the

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   application was that roughly the same amount per
        2   acre, but was the total amount -- I mean, were the
        3   experimental conditions such that one could have some
        4   confidence that the difference is real in these two
        5   graphs?  Not just the slope of the curve but the fact
        6   that one seems to produce twice as much airborne than
        7   the other?  
        8                 MR. KELLEY:  They were performed under
        9   very similar environmental conditions.  The size of
       10   the fields were approximately similar, and sampler
       11   placement was identical in all situations.  So one
       12   would assume from that --
       13                 DR. BYUS:  Do they spray the stone
       14   fruits the same way, air application -- by airplane
       15   or helicopter -- or is that sprayed from the ground?  
       16                 MR. KELLEY:  They do some applications
       17   by airplane, but they also use air blast sprayers
       18   where they're driving ground equipment through the
       19   field with the spray blasted up through the bottom of
       20   the trees as opposed to being up on top, you know,
       21   spraying it down.
       22                 DR. BYUS:  Excuse my ignorance.  
       23                 MR. KELLEY:  Sure.  
       24                 DR. BYUS:  Would you expect more or
       25   less to be in the air or remain in the air under that

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   kind of application?  I assume this was from
        2   airplane.  
        3                 MR. KELLEY:  Yeah, this is aerial.  
        4                 DR. BYUS:  So what would you think? 
        5                 MR. KELLEY:  Well, there's -- it all
        6   depends, again, on droplet size, concentration, the
        7   amount they're spraying, whether they apply it via --
        8   as they say, rotary or fixed wing.
        9                 MR. GOSSELIN:  The EPA has been -- and
       10   we've been following what's called a spray drift task
       11   force looking at off-site movement.  And actually,
       12   what they did find is certain air blast-type sprayers
       13   produce such fine aerosols that you actually in many
       14   instances get more off-site movement than in aerial.  
       15                 And I think because a lot -- not just
       16   in in-state but nationally a lot of agencies have
       17   really been focused on aerial application off-site
       18   movement because it presents such a higher risk that
       19   they have actually been improving the nozzle design,
       20   placement to really reduce the amount of aerosols
       21   coming off the aerial application.
       22                 DR. BYUS:  Okay.  Thank you.  
       23                 MR. KELLEY:  Basically, the gist of
       24   this graph shows that at application or immediately
       25   following application you have high concentrations in

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   the air which the next day dropped significantly for
        2   both groups and then finally after three, four, five,
        3   six days, it's down to an amount undetected -- well,
        4   actually, they were detected.  But it was down to
        5   approximately one part per trillion.
        6                 Next.
        7                 And this is a --
        8                 DR. FROINES:  What's the frequency of
        9   spraying?  Once spraying occurs, and then when do
       10   they go back and spray a second time?  
       11                 MR. KELLEY:  Oh, for the fields?  Most
       12   fields are only sprayed once with methyl parathion. 
       13   So I mean, they could spray, you know, this 640 acres
       14   today and then tomorrow spray the next one or spray
       15   the both of them, you know, the same day.  
       16                 But most methyl parathion applications
       17   are singly, made once, to the commodity.  And as you
       18   start making more, then you start getting into some
       19   very severe re-entry and preharvest restrictions.  
       20                 Does that answer your question?  Okay.
       21                 This Seiber -- or excuse me, this graph
       22   is taken after a Seiber and McChesney study they did. 
       23   They were out in rice fields in 1977 sampling, and a
       24   methyl parathion application occurred to a field
       25   adjacent to where they were sampling.  And so they

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   decided to see if methyl parathion would be found,
        2   and indeed it was.
        3                 And their samplers were -- basically
        4   this graph is hours after application, and then
        5   samplers that were set up immediately following
        6   application, methyl concentrations were approximately
        7   95 parts per trillion.  Ten hours after
        8   application -- which is right here (indicating) -- it
        9   was approximately 108 parts per trillion.  
       10                 However, within two days
       11   concentrations -- concentrations had dropped to
       12   approximately 4.5 and 4.7 parts per trillion.
       13                 DR. FROINES:  How far were these
       14   samplers from --
       15                 MR. KELLEY:  The field?  They were 20
       16   meters away from the field?  
       17                 DR. SEIBER:  It says back in the
       18   report -- it says the border of a tree to field, so
       19   I'm assuming just a matter of a few meters.  But I
       20   would have to look back to -- 
       21                 DR. FROINES:  Border of a tree to the
       22   field?  
       23                 DR. SEIBER:  Yeah.
       24                 Do you remember?  
       25                 MR. KELLEY:  That's why I said 20

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   but -- 
        2                 UNIDENTIFIED SPEAKER:  I believe it's
        3   20 yards.  
        4                 MR. KELLEY:  Twenty yards, yeah.  
        5                 DR. SEIBER:  Twenty yards.  Okay.  
        6                 MR. KELLEY:  About 17 meters, then.
        7                 DR. BYUS:  Does that fit with the half
        8   life that you said exists maybe for methyl parathion? 
        9                 MR. KELLEY:  The one that I had
       10   mentioned earlier was information, I think, just come
       11   into the department as part of the public comment
       12   period.  It has not been fully evaluated.
       13                 DR. BYUS:  What was it?  You said the
       14   half life was --
       15                 MR. GOSSELIN:  13, 18 hours.  
       16                 MR. KELLEY:  Yeah, that's -- in an
       17   environment that's what they were proposing.  But in
       18   the laboratory the half life they were getting was
       19   down to 30 minutes.
       20                 DR. SEIBER:  Yeah, it's probably -- the
       21   methyl parathion's put in the water -- in the rice
       22   field water, so it probably reflects the hydrolysis
       23   in the water, not the breakdown in the air.  That
       24   would be my guess.  
       25                 MR. KELLEY:  These half lives that I

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   was quoting, they were setting up chambers in which
        2   they dropped the air pressure until methyl parathion
        3   would volatilize, and then they would expose that to
        4   wave -- you know, lights of all sorts of different
        5   wavelengths.  And they were measuring the actual half
        6   life of the breakdown of methyl parathion in that.
        7                 DR. SEIBER:  In the air.  
        8                 MR. KELLEY:  In the air.  
        9                 DR. SEIBER:  Yes.
       10                 MR. KELLEY:  So it's --
       11                 Next.
       12                 And this is just more general
       13   information from the literature on methyl parathion
       14   concentrations.
       15                 A variety of studies that were
       16   conducted from 1971 through 1983; a variety of
       17   authors or several authors either conducted their
       18   studies in rural areas in the east and also the west. 
       19   Riverside was also one of their sample sites.  And
       20   the -- these are some of the concentrations that they
       21   came up -- that they detected.  
       22                 In Mississippi the highest
       23   concentration they detected is right here
       24   (indicating):  191 parts per trillion.  And in
       25   various other places it was anywhere from 73 parts

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   per trillion to approximately .5 parts per trillion.
        2                 Next.
        3                 DR. FUCALORO:  Can you go back to that. 
        4                 You have Mississippi, and then you have
        5   below it three years, '72 through '74 inclusive;
        6   right?  
        7                 MR. KELLEY:  Correct.
        8                 DR. FUCALORO:  Now, what -- that's also
        9   Mississippi '72 through '74 inclusive?  
       10                 MR. KELLEY:  Right.
       11                 DR. FUCALORO:  And this is just a
       12   Mississippi no year indicated; right?  1976 was --
       13   oh, I see.  Weekly samples taken from -- why is that
       14   number so large?  I mean, there's a -- it's so much
       15   larger than all the others.  I mean, is there
       16   anything special about that?  Is that something to
       17   be -- 
       18                 MR. KELLEY:  There's nothing mentioned
       19   in the actual paper.  It could have been the fact
       20   that they sat out there and either there was a lot of
       21   use or possibly, you know, they happened to set it
       22   out at the time when the plane flew over the sampler. 
       23   You know, it did not state in the paper.
       24                 DR. FUCALORO:  It had no statement. 
       25   Because just looking at -- looking at the Jackson and

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   Lewis paper the highest was 700 parts per trillion. 
        2                 MR. KELLEY:  And this one right here is
        3   only 191 parts per trillion.
        4                 DR. FUCALORO:  I guess.  All right.
        5                 DR. FRIEDMAN:  Is the numbers under
        6   Mississippi supposed to be the breakdown of that
        7   total?  
        8                 MR. KELLEY:  Yes.
        9                 DR. FRIEDMAN:  Why wasn't the maximum
       10   achieved in any one of those years?  
       11                 DR. FUCALORO:  That's right.  And you
       12   know, if you add up the total number, 52 times 3, you
       13   do get 156, which implies that what you're saying is
       14   correct.  It is the total.  I mean, it does imply
       15   that.  But yet it's strange.  
       16                 MR. KELLEY:  I have no answer for that.
       17                 DR. FUCALORO:  Look at that again. 
       18                 MR. KELLEY:  I'll have to get back
       19   and --
       20                 DR. FUCALORO:  Yeah.  You have to look
       21   it up.  
       22                 DR. FRIEDMAN:  The other numbers make
       23   sense but not the two columns under "Maximum Value."
       24   The two columns under "Maximum Value" don't make
       25   sense because the maximum should have occurred at

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   least one of those years.  
        2                 MR. KELLEY:  Correct.  I agree with
        3   that.  Like I said, I'll have to go back and check
        4   that out in my report and also the paper there.
        5                 DR. FROINES:  But the data is
        6   considerably skewed so the geometric mean would be
        7   probably pretty low, huh?  
        8                 MR. KELLEY:  Yeah, because they do have
        9   a lot of non-etects.  They --
       10                 DR. FUCALORO:  Is it a geometric mean?  
       11                 DR. FROINES:  No, this is an arithmetic
       12   mean.  
       13                 DR. FUCALORO:  An arithmetic mean?  
       14                 MR. KELLEY:  Correct.  
       15                 DR. FROINES:  But my guess is that it's
       16   going to be skewed.  
       17                 MR. KELLEY:  Could you explain?  I'm
       18   sorry.  I don't understand.  
       19                 DR. SEIBER:  I think it's always a
       20   problem when you use the maximum value out of --
       21   let's say make 50 measurements and you take the max,
       22   that number's not going to hold up.  It's not going
       23   to show much consistency, I wouldn't think.  And it
       24   probably is way out on the extreme of distribution
       25   here.

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1                 DR. GLANTZ:  That's true.  But the
        2   point -- I mean, I agree with you, but the point
        3   they're making is that the maximum should have been,
        4   if you look at the table here, 791.
        5                 DR. SEIBER:  I agree with that.  I
        6   don't know what -- I don't remember that.  
        7                 MR. KELLEY:  Right.  It's in '73.  So
        8   like I said, I have to go back and look at this. 
        9   It's --
       10                 Next.
       11                 In 1986 DPR requested the state Air
       12   Resources Board to document the presence of methyl
       13   parathion in ambient air and in air associated with
       14   specific pesticide application.  And the ARB
       15   subsequently requested the Environmental Tox
       16   Department at the University of California Davis to
       17   perform monitoring studies.
       18                 Most samples were collected in the
       19   communities of Maxwell and Williams in Colusa County
       20   and Trowbridge and Robbins in Sutter County.  And the
       21   background samples were collected in Yellow County on
       22   campus of University of California Davis.
       23                 Methyl parathion was detected in both
       24   Colusa and Sutter Counties.  And methyl parathion
       25   concentrations ranged from 0.05 to 2.8 parts per

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   trillion in Colusa with the highest 24-hour average
        2   of three samples' concentrations methyl parathion was
        3   2.4 parts per trillion measured at Maxwell.
        4                 DR. FRIEDMAN:  It looks like 26.  
        5                 MR. KELLEY:  Actually, it's 2.4 -- no. 
        6   It's 2.4 on the graph here.  The decimals are wrong. 
        7   That should be 2.5 instead of 25 there.
        8                 DR. FUCALORO:  Where's that?  The Y
        9   axis is up by a factor of 10?  
       10                 MR. KELLEY:  Yeah, the Y axis is up by
       11   a factor of 10 on here.
       12                 DR. FUCALORO:  Is it fair to say that
       13   the -- there were two studies on the oxon, Maxwell
       14   and Williams; right?  
       15                 MR. KELLEY:  Correct.
       16                 DR. FUCALORO:  Are we talking about a
       17   three-to-one ratio in parathion versus paraoxon? 
       18                 MR. KELLEY:  I think it's close to five
       19   to one.  
       20                 DR. FUCALORO:  Five to one.  
       21                 MR. KELLEY:  And then I guess Tareq
       22   will discuss that more when he talks.
       23                 DR. FUCALORO:  All right.  
       24                 DR. FROINES:  But here's my problem
       25   with this:  I don't know where the samplers are

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   placed, and I don't know the temporal, the
        2   characteristics so that I don't know what the
        3   take-home lesson is.  
        4                 Did somebody put a sampler out -- some
        5   samplers out in some place at some time and -- what I
        6   am -- when I'm all finished, I don't -- tell me what
        7   the take-home lesson is.  
        8                 MR. KELLEY:  Okay.  Samplers were
        9   located within the communities, generally within a
       10   quarter to a half a mile from where methyl parathion
       11   was being applied.  
       12                 And I think the farthest case the
       13   sampler was placed would be a mile from where the
       14   actual samples were collected, and that, I think, was
       15   Maxwell -- was Williams.
       16                 Samplers were collected for 24 hours in
       17   all cases.  They were collected four days a week
       18   determining on just how Davis was able to get out and
       19   sample.
       20                 And basically the take-home message for
       21   this is that they detected it in the air.
       22                 DR. FRIEDMAN:  What is the oxon -- what
       23   do the oxons mean?  
       24                 MR. KELLEY:  That's methyl parathion
       25   oxon.  When methyl parathion is -- the sulfur's

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   replaced by an oxygen molecule.
        2                 DR. FROINES:  My point is simply this: 
        3   Numbers like this end up getting used for a variety
        4   of uses, and my point is I like to know things like
        5   wind directions and location of samplers and time of
        6   sampling and all the various parameters that help you
        7   define the nature of the sampling protocol.  And then
        8   I can interpret it.  Without that it's a
        9   two-dimensional picture.  
       10                 MR. KELLEY:  Correct.  Excuse me for a
       11   second.
       12                 DR. FROINES:  It's just a point, just a
       13   general issue.  
       14                 MR. KELLEY:  That information is in the
       15   document.  And I see your point about how it makes it
       16   better for a discussion to -- for me to have it.  I
       17   just don't have that here right now.
       18                 DR. SEIBER:  Yeah.  For example, there
       19   was a -- there's, I believe, an acres treated table,
       20   table 9 in your document --
       21                 MR. KELLEY:  Correct.  
       22                 DR. SEIBER:  -- that says how many
       23   acres were treated in the vicinity of these.  
       24                 Now, it's still not a good answer to
       25   your question.  Specific fields, you know, wind going

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   from here to there.  I don't think that level of
        2   detail was in this study.
        3                 DR. FUCALORO:  In fact, we never -- we
        4   hardly ever see that level of detail.  
        5                 DR. FROINES:  I think that it might be
        6   useful if we start having some GIS maps developed so
        7   that we can look at this kind of data in its
        8   entirety.          
        9                 MR. KELLEY:  I agree with that.  I do
       10   have a juxtaposition of -- in fact, if you go to the
       11   next two -- the next one and the one after that one,
       12   the overhead there, I have a juxtaposition here of
       13   used versus detections.
       14                 DR. FROINES:  Which one am I looking
       15   at?  I'm sorry.  
       16                 MR. KELLEY:  That would be this one
       17   here (indicating).
       18                 DR. FUCALORO:  It's on the back.  
       19                 MR. KELLEY:  And in this graph
       20   basically what I have plotted here is the figures for
       21   detection are the black symbols.  In Maxwell it would
       22   be the diamond, and Williams it's the circle.  
       23                 And then the actual value of the --
       24   of -- the amount of methyl parathion applied, which
       25   is on the right side on the Y axis, then you can see

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   that on this at least it shows some sort of a
        2   correlation of the fact that it's being applied and
        3   that you detected it in the air.
        4                 DR. FROINES:  You see, my sense is that
        5   what happens is you go out and you -- people debate
        6   the NOEL level for methyl parathion and the NOAEL
        7   level, and we talk about health effects.  And so we
        8   have -- what we're concerned about is
        9   population-based health effects.
       10                 So what I think we need then is a
       11   population-based exposure assessment so that in fact
       12   the -- we know who's being exposed over what periods
       13   of time over what regions with what proximity the
       14   samplers and so on and so forth.
       15                 In other words, so much of the exposure
       16   assessment is two-dimensional often, and this is not
       17   a criticism.  Don't -- this is just for -- I think
       18   over time what we want is the exposure -- rather the
       19   airborne concentrations should be collected in such a
       20   way to give us information on population-based
       21   exposure which is what the endpoint -- which is the
       22   endpoint of need if you want to ask about health
       23   effects.  
       24                 MR. KELLEY:  Okay.  I can see that. 
       25   But unfortunately what we find with a lot of

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   pesticide use is that the area that we would prefer
        2   to sample would be the area of high use.  
        3                 It's -- and so therefore, in most cases
        4   that tends to be in areas that are -- you know,
        5   generally removed from high concentrations of human
        6   population.
        7                 DR. SEIBER:  Yeah, these little towns
        8   are surrounded by rice fields so, you know, they
        9   would presumably be the worse case -- the population
       10   with the highest exposure, and I think that's
       11   probably why you selected them.  
       12                 DR. KENNEDY:  The reality is that that
       13   information is simply not available.  You're looking
       14   at community-based exposure levels.  
       15                 MR. GOSSELIN:  I think on one hand what
       16   Dr. Froines is talking about is having the geographic
       17   basis of where -- how the monitoring was conducted,
       18   and I think it's fair that we should continue to
       19   monitor in the high use areas as the most
       20   conservative approach.  
       21                 You can then take that information and
       22   bridge that to presumably any theoretical area where
       23   you would have populations.  But I think what we'll
       24   find is --
       25                 DR. FROINES:  But then you also have to

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   define the criteria for that sampling, which is, for
        2   example, what is the prevailing wind direction? 
        3   Which way does it flow when you sample in the morning
        4   and in the evening?  Is there an off flow and an --
        5   you know, so on and so forth.  You know, there's lots
        6   of different variables.  
        7                 So that what I'm saying is if we're
        8   going to rely -- have to rely on exposure
        9   measurements in pesticides as opposed to ambient
       10   concentrations, then the characterization of that
       11   exposure becomes really crucial.  And without
       12   knowledge of the character -- of the nature of it,
       13   you can't judge it.
       14                 DR. BYUS:  I have a related question. 
       15   Excuse my ignorance.  But if you actually -- if you
       16   assume you're spraying one to three pounds per acre
       17   and the planes fly in at -- I don't know, how high is
       18   it?  
       19                 If you took the volume of air and, you
       20   know, immediately after spraying is complete, the
       21   concentration in the air is what?  In like parts per
       22   trillion, it must be.  
       23                 MR. KELLEY:  Parts per million.
       24                 DR. BYUS:  Or million.  Or whatever it
       25   is.  It must be quite high.  And then it would be

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   interesting -- as a scientist.  I mean, we're all
        2   scientists, but I mean it would be nice to have some
        3   monitoring, something that monitored with time in the
        4   middle of the field right after -- maybe they do
        5   this, Jim.  I don't know.
        6                 DR. SEIBER:  Yeah, they do some.
        7                 DR. BYUS:  Right after you spray it, it
        8   should be extremely high, and how fast does that fall
        9   off with time even in the field.  I have in the
       10   middle of it.  I have some -- you know, I can't --
       11   it's hard for me to realize what that would be.  
       12                 And then if you had the data from
       13   surrounding the field say in certain places with time
       14   and compared all that data, you'd have a really good
       15   picture of the exposure.  I mean, do people do this?  
       16                 DR. SEIBER:  Yeah, they do two kinds of
       17   things:  one is put them out in the towns; and put
       18   them right down -- right next to a treated field to
       19   get the absolute worse situation.  I'm not sure.  Did
       20   we do that for methyl parathion?  
       21                 MR. KELLEY:  I don't know.
       22                 DR. SEIBER:  Maybe we'll get to it.  
       23                 MR. GOSSELIN:  But I think also in the
       24   future is as monitoring went on over more recently,
       25   more data has been collected including the weather

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   data that will allow more modeling out to
        2   characterize what levels are going to be out there. 
        3                 MR. KELLEY:  And actually, my last
        4   slide here -- or penultimate, I should say -- no, no. 
        5   The one just before this.  Yes.  
        6                 This is concentrations of methyl
        7   parathion in the air following an application.  And
        8   samplers in this situation were placed approximately
        9   17 meters from a field, 20 yards.     
       10                 Treatment field size was 80 acres, and
       11   80 pounds of methyl parathion or one pound of active
       12   ingredient per acre was applied.  This was done in
       13   May -- June, I believe, and I don't have air
       14   temperatures and/or wind directions for this.  
       15                 But from the background there was no
       16   methyl parathion detected.  The first sample
       17   collected was collected during application and for
       18   one hour following application.  
       19                 And you can see that in the samplers
       20   that were located north of the field the
       21   concentration of methyl parathion was approximately
       22   50 parts per trillion, whereas, samplers to the south
       23   side of the field were only 20 parts per trillion.  
       24                 In samples collected one to three hours
       25   following application these concentrations dropped to

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   20 parts per trillion for those south of the field
        2   and to approximately 17 parts per trillion for the
        3   sampler located north of the field.
        4                 At three to seven hours the sample
        5   south of the field concentrations increased to
        6   approximately 27 parts per trillion, whereas, to the
        7   north the concentration dropped to approximately 10
        8   parts per trillion.
        9                 Samples collected 7 to 18 hours, the
       10   concentration rose again to approximately 30. 
       11   Samples north of the field, they dropped to
       12   approximately 10 for samplers located south of the
       13   field.  
       14                 And then from 18 to 25 hours, 25 to 48
       15   hours -- 49 hours, and the last which is 49 to 73
       16   hours, concentrations were all below 10 parts per
       17   trillion.  
       18                 And I don't have the data right in
       19   front of me, but I can say anecdotally that wind
       20   direction at this point in time where the
       21   concentrations to the north dropped so much, the wind
       22   was blowing more towards the east and away from the
       23   samplers and then back at the 7 to 18 hours as the
       24   winds had taken again a northerly direction so that 
       25   depending on which way the wind was blowing. 

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1                 Which -- and from this data is where
        2   we've modified our request to the Air Resources Board
        3   and now instead of having north and south samplers we
        4   have them on the east and west also and request them
        5   to collect a lot more -- wind direction once every
        6   six minutes, is it, I think?  They're averaging on a
        7   six-minute basis so that we can get a lot closer to
        8   what's actually happening on the field.
        9                 DR. BYUS:  And again, I -- the aerial
       10   spraying is accurate, so I imagine it's very accurate
       11   so they don't --  you didn't actually spray the
       12   samplers?  
       13                 MR. KELLEY:  No, I didn't.
       14                 DR. BYUS:  So this is a true --
       15                 DR. SEIBER:  Commercial field.
       16                 DR. BYUS:  But those other really high
       17   values on the other table might have occurred, but
       18   you don't know.  One might think they occurred
       19   through direct application.  
       20                      You said it was 17 meters.  I
       21   don't know whether -- they spray that well, do they? 
       22   I mean -- but in this study they must have is what
       23   you're saying.  
       24                 MR. KELLEY:  And in conclusion --
       25                 DR. FUCALORO:  Every once in a while

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   they get the farmhouse.  
        2                 MR. KELLEY:  Actually, they do.  
        3                 In conclusion methyl parathion is an
        4   organophosphate insecticide that's used to control a
        5   variety of insects and other arthropod pests in a
        6   variety of crops in California.  
        7                 Applications of methyl parathion have
        8   decreased from a high of over one million pounds
        9   previously in 1977 to 72,000 pounds in 1991.  Average
       10   use for '86 through '95 was approximately 140,000
       11   pounds active ingredient.  
       12                 Methyl parathion is applied to a
       13   variety of crops.  Before 1990 rice accounted for
       14   most methyl parathion applications.  However, since
       15   1990 the major use of methyl parathion has shifted
       16   from rice to stone fruit and grapes.
       17                 Methyl parathion is applied in all
       18   counties throughout all months in the year in
       19   California.  Most applications are made during the
       20   months of May -- excuse me, of March, April, May,
       21   June, and July.  Peak applications occur from
       22   mid-June through mid-July.
       23                 Methyl parathion air concentrations
       24   reported in the literature range from 0 to 688 parts
       25   per trillion, and formulation plays an important role

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   in the atmospheric loading of methyl parathion.
        2                 In ambient air studies conducted in
        3   California air concentrations of methyl parathion
        4   ranged from 0 to 2.8 parts per trillion.
        5                 DR. FROINES:  I don't understand
        6   something about that sentence because this last
        7   overhead you showed showed levels up to 50 parts per
        8   trillion.  
        9                 MR. KELLEY:  Correct.  I said in
       10   ambient air studies.  I will get to that one in just
       11   a second.  
       12                 Methyl parathion concentrations, which
       13   is my last conclusion, measured at rice fields
       14   following application were 47 per trillion,
       15   decreasing to less than 3 parts per trillion after 48
       16   hours.
       17                 The ambient air studies -- perhaps I'm
       18   using "ambient" incorrectly, but those are the
       19   studies that we have conducted which are not
       20   associated with specific applications but the
       21   monitoring is conducted in areas where applications
       22   are occurring during the time of high use.
       23                 And finally, methyl paraoxon is a
       24   breakdown product of methyl parathion, and ambient
       25   concentrations ranging from 0 to 0.73 parts per

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   trillion.
        2                 That's basically it.  Any questions?
        3                 DR. FUCALORO:  Yeah.  You know, just on
        4   the first page, on that first slide, just a small
        5   thing.  
        6                 I don't quite understand that
        7   solubility.  It says 55 to 60 milligrams per liter in
        8   water at 250 degrees centigrade.  Now, I don't think
        9   you mean 25 degrees centigrade either considering the
       10   fact that at 25 degrees centigrade it's somewhere
       11   between 13 and 15 milligrams per liter.  
       12                 So I'm not sure what that means, that
       13   number.  Super heated water?  I'm putting it in here. 
       14   I don't know.  Just that.  I mean, it's nothing --
       15   nothing that affects any conclusion.
       16                 And again, I just point out the Henry's
       17   Law Constant really I'm pretty sure is temperature
       18   dependent.  I don't see how it can not be temperature
       19   dependent.  
       20                 Because it goes is the log -- I mean,
       21   if it goes like normal vapor pressures, it goes is
       22   the log, you know -- is the log of the heat of
       23   vaporization times one over the temperature.  
       24                 MR. KELLEY:  Yeah, you're correct. 
       25   Since you mentioned it.  I didn't have the time to

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   change it.  It's 25 degrees Celsius.
        2                 DR. FUCALORO:  That's 25 -- the
        3   solubility?  
        4                 MR. KELLEY:  Yeah, the 250 should be
        5   25.  
        6                 DR. FUCALORO:  Yeah, but then it's at a
        7   variance with what you say in your report, I believe. 
        8                 MR. KELLEY:  No, in the report I say
        9   it's 55 to 60 milligrams per liter in water and 25
       10   degrees --
       11                 DR. FUCALORO:  Maybe I just read it
       12   wrong.  It's quite possible.  I have made mistakes
       13   before.  It's hard to remember when, but I've made
       14   mistakes.  
       15                 MR. KELLEY:  Any other questions?  
       16                 MR. GOSSELIN:  The next report will be
       17   the hazard identification.
       18                 DR. FROINES:  I think -- just to make
       19   one comment.  I think there's lots of room for
       20   expanded exposure characterization based on these
       21   limited data, and I think we ought to talk about how
       22   to incorporate GIS approaches to some of this
       23   exposure modeling.  Because we all do it in air
       24   pollution work, but it's not GIS --
       25                 DR. KENNEDY:  What is GIS?  

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1                 DR. FROINES:  Geographic Information
        2   Systems.
        3                 DR. FUCALORO:  It's a database that
        4   gives altitudes and --
        5                 DR. FROINES:  Makes maps.
        6                 DR. FUCALORO:  -- makes maps.  
        7                 DR. KENNEDY:  Are those formulations
        8   routinely available for this sort of data?  
        9                 DR. FROINES:  Yeah.
       10                 DR. KENNEDY:  So it's just a matter of
       11   providing --
       12                 DR. FROINES:  Do you have any -- you
       13   don't have any with you, do you?  
       14                 UNIDENTIFIED SPEAKER:  No, I don't. 
       15   With all the databases that EPR has with pesticides,
       16   I think they can easily be combined with 
       17   geographic --
       18                 DR. FROINES:  You can develop a map of
       19   the geographical area.  You can put in towns, you can
       20   put in farms, you can put in the pesticides, and you
       21   can overlay it all.  And it's all done in a computer. 
       22                 So you can end up with a complete
       23   picture of all pesticide use in terms of amount,
       24   timing, every variable you would want to.  It is in
       25   the computer, and you can develop overlaying maps.

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1                 DR. KENNEDY:  If that's available.  We
        2   ought to have it.  Sure.  
        3                 MR. GOSSELIN:  We do sort of extensive
        4   work with that.  I mean, the new support information
        5   we have now is digitized, and we routinely use that
        6   in GIS.  We have done it for endangered species
        7   protection and a lot of other programs.
        8                 Part of the dilemma we're facing is a
        9   lot of -- the work that was done for this predates
       10   having the level of detail in the use reports where
       11   we don't have it down to the actual geo codes to know
       12   where the use was.
       13                 But you're absolutely right.  I think
       14   you'll see in the subsequent reports, in the more
       15   contemporary assessments we have, you'll see that it
       16   will be in GIS format.  That will be another tool to
       17   help evaluate what all this data means.
       18                 DR. FROINES:  You know, Peter, one of
       19   the things that comes up, you know, that EPA went and
       20   developed these new particle standards and standards
       21   for ozone, and then they -- in their new latest RFA
       22   on grant for particle centers they asked a question
       23   what's the relationship between ambient monitoring
       24   and exposures to human beings, to people.  
       25                 And so you have this disconnect of

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   the -- of the -- you have emission sources on the one
        2   hand, you have ambient monitoring, and then you have
        3   personal exposure questions.  
        4                 And so but within that continuum there
        5   are -- it's very unclear what the relationship is
        6   between ambient monitoring and personal exposure. 
        7   And it seems to me that one of the problems that
        8   regulatory agencies get into is they get into doing
        9   ambient monitoring.  
       10                 That's what they do.  They set the
       11   stations out.  But then you go later and you say,
       12   "Well, are there any health effects from breathing
       13   this stuff in the air?"  
       14                 Well, then the ambient monitoring
       15   stations can't help you answer that question because
       16   it's really not directed towards people's exposure. 
       17   And I think that over time we need to develop our
       18   sampling systems such that they can actually have
       19   implications or relevance to questions about human
       20   health that we might want to ask at some point in
       21   time.  
       22                 And it's that kind of notion that is
       23   where the regulators and the -- in the sense the
       24   health science community differ because the
       25   regulators want to see if people are over certain

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   values.
        2                 But what we're really interested in is
        3   whether or not these exposures have actually affected
        4   anybody's health.  And it's within that context that
        5   I think we have to look at how these sampling
        6   programs are designed, and GIS modeling for
        7   pesticides is the state the art.  
        8                 And Lupita back there has spent almost
        9   a year in Mexico doing precisely that and trying to
       10   figure out how you then relate some of that to actual
       11   person exposure.
       12                 MR. GOSSELIN:  We're going to have a
       13   slight change in the format in the presentation.  I
       14   think it's going to be more helpful.  And instead of
       15   the getting into the exposure assessment immediately
       16   like we did last time, we're going to have Ruby Reed
       17   give a presentation on the hazard ID portion that
       18   will then bridge into the exposure assessment, and
       19   then she'll follow up with the risk characterization
       20   and risk assessment, which I think flows more
       21   logically through the process.
       22                 DR. FROINES:  Are we talking -- I think
       23   we're talking about closing about 3:30.  
       24                 DR. FRIEDMAN:  Some of us are leaving
       25   at 3:00.  At least I'm leaving at 3:00.

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1                 DR. FROINES:  Who's leaving at 3:00? 
        2   Gary is.  Stan's out making important phone calls. 
        3   Well, right now we don't have a quorum at all.  Maybe
        4   we could get some of the quorum into the room.  So
        5   are we talking about -- if Gary leaves, we still have
        6   a quorum.  If we can get Stan off the telephone.  
        7                 DR. FRIEDMAN:  Do you need a quorum to
        8   listen to a presentation?  
        9                 DR. FROINES:  I don't know to answer
       10   that.  That's the lawyers' --
       11                 DR. FROINES:  George.  
       12                 DR. ALEXEEFF:  I just have a question. 
       13   We have -- OEHHA has some findings on the document. 
       14   It's probably not necessary for us to verbally
       15   present them.  They're fairly self-explanatory. 
       16   Last -- for DEF, when we began to present it, it was
       17   clear it would be redundant to some of the
       18   presentation of the DPR staff.
       19                 So I think in that sense maybe we can
       20   just -- I think we can just submit them to the panel
       21   for consideration.  They can -- we can look at them. 
       22   And there's no reason for an OEHHA presentation
       23   because we generally concur with their report.
       24                 DR. FROINES:  Well, that's good to
       25   know.              

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1                 DR. ALEXEEFF:  Not to steal your
        2   thunder, but I just thought --
        3                 DR. FROINES:  No blood on the floor. 
        4                 We are going to take this up next
        5   month, and I'll -- and I know that -- see, I have to
        6   be back at UCLA by 6:00.  Gary's leaving at 3:00.  So
        7   we have -- I'd like to leave about 3:30.  So if we
        8   can go until 3:30 and just start next -- why don't we
        9   say 3:30 is our cutoff, and then we'll start next
       10   time where we didn't get to.  
       11                 Is that okay?
       12                 DR. GLANTZ:  I'm back.  Sorry.
       13                 DR. FROINES:  You're our quorum because
       14   Seiber may have left.  No, he's still here.  
       15                 Go ahead.  
       16                 DR. REED:  Thank you.  I am Nu-May
       17   Reed.  People call me Ruby.  I answer to both names. 
       18   But if you call our department and ask for Nu-May,
       19   you'll get a no for an answer.  That's what happened
       20   to Craig.  
       21                 DR. BYUS:  You are really there,
       22   though; right?  
       23                 DR. REED:  Yes, I have been.  
       24                 Can we have the lights off, please.   
       25                 The next slide is just going to be sort

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   of a graphic location in terms of what I will be
        2   presenting with respect to the four components of
        3   risk assessment.
        4                 DR. FROINES:  We have had handouts. 
        5                 DR. REED:  Yes.  
        6                 Tareq, could I have the next slide,
        7   please.  
        8                 This particular slide is not in your
        9   handout.  As I said, this is just sort of a graphic
       10   presentation in terms of what I will be presenting
       11   now.  It will be on the hazard identification and
       12   dose response assessment.  And then Tareq will come
       13   back to present the exposure assessment, and then I
       14   will come back and present the risk characterization.
       15                 Next slide, please.
       16                 A well-characterized mechanism of
       17   toxicity of methyl parathion is the inhibition of
       18   cholinesterase and cause an accumulation of
       19   neurotransmitter acetylcholine at the nerve
       20   junctions, and the consequences are manifested in
       21   neurological signs and symptoms of both the
       22   peripheral and central nervous systems.  
       23                 The estimated rates of methyl parathion
       24   absorption through oral and inhalation routes are 100
       25   percent.  Methyl parathion crosses the brain barrier

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   and the placenta.  
        2                 Methyl parathion is metabolically
        3   activated to methyl paraoxon which inhibits
        4   cholinesterase by binding to its active site.  Methyl
        5   parathion is eliminated as para-nitrophenol in the
        6   urine.  
        7                 Age specific sensitivity to methyl
        8   parathion is evident in rats.  Neonates can be
        9   approximately tenfold more sensitive than the adults
       10   to the acute toxicity of methyl parathion.
       11                 The activities of paraoxonase, the
       12   enzyme that breaks down methyl paraoxon, can vary in
       13   human population by more than sixtyfold, and this is
       14   illustrated as a -- sort of a profile of
       15   polymorphism.  
       16                 Next slide, please.
       17                 The endpoints of toxicity have been
       18   identified in the following areas:  
       19                 In humans symptoms of acute poisoning
       20   of methyl parathion are typical of cholinergic
       21   abundance such as salivation, lacrimation, myosis,
       22   defecation, urination, headaches, dizziness, labored
       23   breathing, twitching, convulsion, and death.  It
       24   depends on the dose.  
       25                 Methyl paraoxon acute -- parathion

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   acute poisoning can result in intermediate syndrome
        2   which typically appears one to four days after
        3   successful treatments of cholinergic crisis. 
        4   Intermediate syndrome includes myopathy, respiratory
        5   paralysis, nerve palsies, and muscle weaknesses.
        6                 In animal studies acute and subchronic
        7   exposure to methyl parathion in terms of
        8   neurotoxicity results in plasma, RBC, and brain
        9   cholinesterase inhibition.  And cholinergic effects
       10   include similar things as I have sort of enumerated
       11   for the humans:  lacrimation, salivation, shivering,
       12   muscle fasciculation, labored breathing, and other
       13   neurological effects.  Neurobehavioral changes have
       14   also been identified.
       15                 Chronic exposure to methyl parathion in
       16   the animals resulted in cholinesterase inhibition
       17   again and tremors, alopecia, body weight changes,
       18   paralysis, as well as myelin degeneration of nerves.
       19                 Long-term feeding studies in rats and
       20   mice showed no clear evidence of oncogenicity
       21   although data indicated that methyl parathion has
       22   genotoxic potential.
       23                 In terms of reproductive developmental
       24   effects methyl parathion decreases the survival in
       25   body weight of rat pups in two- and three-generation

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   reproductive studies and can cause male and female
        2   reproductive toxicities also.
        3                 Methyl parathion causes lower fetal
        4   body weight, increased resorption, reduced pup
        5   survival, and abnormalities and variations of the
        6   fetal ossification in rats and rabbits. 
        7   Neurobehavioral changes can result from in utero
        8   exposures.  
        9                 Methyl parathion is not known to show
       10   organophosphorous-induced delayed neuropathy in hens.
       11                 Methyl parathion suppresses the immune
       12   system, and methyl parathion causes hematological
       13   changes which includes decreased RBC, hemoglobin, and
       14   hematocrit.
       15                 Next slide, please.
       16                 There's no inhalation studies available
       17   for directly establishing the NOELs for the
       18   inhalation exposures, so oral NOELs are used to
       19   assess the risk of inhalation exposures.  
       20                 There's two acute NOELs identified for
       21   risk assessment:  one is a human NOEL at 0.31
       22   milligram per kilogram a day; and based on the LOEL,
       23   just slightly above that level, which is 0.34
       24   milligram per kilogram a day.  
       25                 And the endpoints identified at the

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   LOEL are at the plasma and RBC cholinesterase
        2   inhibition.  And the figure that I presented here in
        3   the overhead represents the individual that has the
        4   highest inhibition.
        5                 DR. SEIBER:  Is the -- is the L --
        6   let's see, NOEL calculated from the LOEL, or are they
        7   both -- 
        8                 DR. REED:  No.
        9                 DR. SEIBER:  What's the relationship
       10   between those?  They seem awfully close together. 
       11                 DR. REED:  Right.  Right.  There were
       12   just a group of five volunteer human subjects being
       13   dosed with different amounts, and they have a very
       14   close range.
       15                 DR. BYUS:  It's one of the most poorly
       16   designed studies I've ever read.  
       17                 DR. REED:  You're correct.  
       18                 DR. BYUS:  I encourage you all to read
       19   about it in the document to see how poor.  And the
       20   fact that EPA, according to your document, actually
       21   used this experiment in humans to make regulatory
       22   decisions and do calculations is actually very
       23   appalling to me.  So I encourage you to read it just
       24   so you can -- to Ruby's credit she doesn't think much
       25   of the study either.  

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1                 DR. REED:  And I will -- in the next
        2   round I will talk about the uncertainty factors
        3   associated with all the NOELs that we have determined
        4   here.
        5                 DR. FRIEDMAN:  Excuse me.  Can I just
        6   ask where they got the volunteers and did the
        7   study -- 
        8                 DR. REED:  Prisoners in the late '60s
        9   and early '70s.  
       10                 DR. FRIEDMAN:  I see.  I don't know
       11   that this would pass an institutional review board
       12   anymore.  
       13                 DR. REED:  So I didn't think that that
       14   human NOEL is adequate.  So I've also identified a
       15   NOEL in rats is at 0.1 milligram per kilogram a day. 
       16   And this one is estimated from the LOEL because
       17   there's no NOEL from a group of studies that have all
       18   identified the LOEL at one milligram per kilogram a
       19   day.  And the effects that the LOEL included brain
       20   cholinesterase inhibition, cholinergic signs, pup
       21   survival in the developmental toxicity studies, and
       22   also reproductive studies, and neurobehavioral
       23   effects.
       24                 DR. GLANTZ:  So for No. 2 did you just
       25   take one-tenth of the LOEL?  

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1                 DR. REED:  Correct.  Yes, I did.
        2                 DR. GLANTZ:  But in No. 1 that's a real
        3   NOEL to the extent that crummy study didn't find
        4   anything.  
        5                 DR. REED:  Right.  Sort of real NOELs
        6   because I have the dose divided by 70 kilograms
        7   because the study did not give me the body weight of
        8   the humans.
        9                 Okay.  A list of all the relevant acute
       10   toxicity NOELs and LOELs is presented in table 19. 
       11   And I have two columns.  One is based on
       12   cholinesterase inhibition including plasma and RBC
       13   cholinesterase inhibition, and the other column is
       14   the other effects other than cholinesterase
       15   inhibition.  
       16                 There's also in the document data on
       17   cholinesterase inhibition from acute subchronic,
       18   chronic exposures so that you could read them back
       19   and forth and decide for yourself what will be the
       20   NOELs and LOELs based on plasma and RBC
       21   cholinesterase inhibition.
       22                 DR. FROINES:  Are you assuming that
       23   neurobehavioral effects are related to the
       24   cholinesterase inhibition?  
       25                 DR. REED:  I am not sure.  The only

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   sort of known mechanism is the cholinesterase
        2   inhibition.  However, there's many effects, as I
        3   identified in here, and I'm not sure what are the
        4   mechanisms.
        5                 Next slide, please.  
        6                 In terms of subchronic toxicity,
        7   because the human NOEL was determined for an exposure
        8   duration of 30 days, so theoretically that could also
        9   be used as a subchronic NOEL.  But as I said, the
       10   human NOEL was not very satisfying.  
       11                 I've also identified NOEL from a group
       12   of studies in rats, and, again, in these studies
       13   there's not NOEL.  The lowest dose was having an
       14   effect, so that was the LOEL at 0.2 milligram per
       15   kilogram a day.  
       16                 And so the NOEL extrapolated down by
       17   tenfold would be 0.02 milligram per kilogram a day,
       18   and the effects of the LOEL are brain cholinesterase
       19   inhibition and neurobehavioral effects.  
       20                 DR. GLANTZ:  Now, why did you use a
       21   factor of 10?  
       22                 DR. REED:  This is the default for not
       23   having enough data to do any benchmark dose or
       24   extrapolations or interpolations.
       25                 DR. GLANTZ:  Where does that -- who

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   decided that and why?  
        2                 DR. REED:  This has been sort of a
        3   default for risk assessment, and one of sort of the
        4   maybe not so fancy sort of layman explanation is
        5   because in choosing dose groups for toxicity studies,
        6   usually you're not seeing a distance or the
        7   differences between two doses greater than tenfold. 
        8   Usually it's three- to tenfold.  
        9                 So it's sort of saying that okay. 
       10   Well, if you had included a lower dose and assuming
       11   that point would give you the NOEL, then it's within
       12   three- to tenfold down.  And so that was sort of the
       13   default.
       14                 DR. FUCALORO:  So experience shows you
       15   it's somewhere in the range of 3 to 10.  Is that --
       16                 DR. REED:  Only by considering dose
       17   selection in a study.  So it's a very soft default.
       18                 DR. GLANTZ:  Right.  But like what if
       19   the person had happened to have done the study say at
       20   a dose 10 times the dose they used, then you would
       21   say the NOEL for rats was .2 which in fact when they
       22   did the study they found an effect.  
       23                 So I mean, doesn't that bother you?  
       24                 DR. REED:  It does, because this is
       25   a -- as I said, it's a default, a soft default.  And

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   so that will go into the uncertainty factor --
        2   uncertainty analysis that I was going to show you at
        3   the end.
        4                 DR. FROINES:  I think that one thing
        5   you should be aware of -- and I don't know if George
        6   has seen Dale's latest paper, but Dale Patters has
        7   just written a very large paper on interindividual
        8   variability for non-cancer effects.
        9                 And one of the things that's clear from
       10   his paper is that the tenfold safety factor for
       11   individual intervariability is a wonderful historical
       12   premise but it's wrong in that regulatory agencies
       13   are going to have to look at the issues using more
       14   quantitative techniques now because there is clearly
       15   so much more heterogeneity in humans that the simple
       16   tenfold factor simply isn't adequate.  And if
       17   anybody's interested, I can send you the paper.  
       18                 DR. REED:  That was --
       19                 DR. FROINES:  It's a brilliant piece of
       20   work.  
       21                 DR. REED:  That was sort of indicated
       22   in the database in methyl parathion also.  As I said,
       23   within the human population, for example, just by
       24   looking at methyl paraoxonase which detoxifies methyl
       25   paraoxon, you would have more than sixtyfold of

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   differences within human population, not tenfold. 
        2                 However, we don't know how to translate
        3   that particular enzyme to the wholistic -- the whole
        4   body responses.  It doesn't look like it's one to one
        5   in animal -- in rabbits and rats.  So we don't know
        6   how to translate that.  But it could be greater than
        7   10.  You're right.
        8                 But what I think we're talking about is
        9   going from LOEL down to NOEL, not even getting into
       10   the interspecies extrapolation yet.  So that's
       11   another soft number.
       12                 DR. GLANTZ:  Right.  But the thing that
       13   concerns me --
       14                 DR. FROINES:  I'm not talking about
       15   interspecies.  I'm talking about interindividual. 
       16                 DR. REED:  Right, right. 
       17   Inter-individual.  Correct.
       18                 DR. GLANTZ:  The thing that concerns
       19   me, though, is that you're just assuming that the
       20   NOEL would be an order of magnitude smaller than the
       21   lowest dose that somebody happened to study.  
       22                 DR. REED:  Right, right.  
       23                 DR. GLANTZ:  So but what if they
       24   happened to study a higher dose?  
       25                 DR. REED:  Correct.  Correct.  

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1                 And I -- maybe this is a good time to
        2   bring this up.  In terms of receiving comments, Paul
        3   had mentioned that we received studies, four studies
        4   that we have not seen before.  Amongst the four
        5   studies was one acute neurotoxicity study, and that
        6   was exactly what happened, what you're talking about.
        7                 The LOEL was at 7.5 milligram per
        8   kilogram a day.  However, they have the large space
        9   between that and the next lower dose which is 0.025. 
       10   And so if you were to call a NOEL and a LOEL based on
       11   the study itself, the LOEL would be 7.5.  The NOEL
       12   would be 0.025.  A large distance.
       13                 DR. GLANTZ:  See, that's what I would
       14   do.  Because what that's -- what I interpreted NOEL
       15   as is the small -- is the largest dose that had been
       16   given that produced no detectable effect.
       17                 DR. REED:  Yes, yes.  
       18                 DR. GLANTZ:  So rather than just
       19   saying -- taking the smallest dose that produced an
       20   effect --
       21                 DR. REED:  Right.  
       22                 DR. GLANTZ:  -- and cutting it by a
       23   factor of 10, I think -- to me what it means is it's
       24   the largest dose where you didn't see any effect.  So
       25   in that case I would take the .02 or whatever the

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   number was.  
        2                 DR. REED:  Correct.  Right.  For that
        3   study, yes.  But this group of studies that have the
        4   lowest to LOEL, there is the NOEL attached --
        5   associated with these studies, so that's sort of all
        6   that we can do.  And it comes with a lot of
        7   uncertainties, yes.
        8                 DR. GLANTZ:  But what I would do is say
        9   that you don't know what the NOEL is rather than put
       10   a number down which is really very arbitrary.  
       11                 DR. REED:  Sure, sure.
       12                 DR. GLANTZ:  I'd say a NOEL is unknown. 
       13                 DR. REED:  Sure.  We have a different
       14   term for it, which I did not use in this document. 
       15   Sometimes we use the term as "estimated NOEL" and
       16   then explain how it was estimated.
       17                 DR. GLANTZ:  But I wouldn't even do
       18   that.  I would just say it's unknown.  
       19                 DR. REED:  Okay.  
       20                 DR. GLANTZ:  I mean, that's why you
       21   have -- I mean -- anyway, I've said enough.
       22                 DR. FUCALORO:  Well, you know, it's
       23   hard to know.  I think it's a good point.  Obviously
       24   it's a clear flaw if you give a dosage to
       25   something -- a dosage to some animal or to a human

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   being and you find that there's an adverse effect and
        2   you just say at 10 times the reduced amount there
        3   will be none.  That clearly is -- I don't know what
        4   basis that has.
        5                 But it seems to me, though, there's
        6   another built-in factor when you look at your MOEs;
        7   right?  
        8                 DR. REED:  Uh-huh.
        9                 DR. FUCALORO:  You're looking at
       10   factors of 10 or 100 where the 10 is human studies
       11   and 100 animal studies to put in yet another
       12   buffering, another effect.  
       13                 So if one does what Stan suggests, one
       14   has to look at the reason for putting in the factor
       15   of 10 and 100 in the MOEs.  I mean, there must be a
       16   reason for doing that, and maybe it's just the reason
       17   he's talking about.  I don't know.
       18                 DR. GLANTZ:  I mean, I think it would
       19   be -- 
       20                 DR. REED:  That's a different factor.
       21                 DR. SEIBER:  That's the safety factor
       22   that John was talking about.  
       23                 DR. REED:  Yes, that John was talking
       24   about.  
       25                 DR. SEIBER:  That and the interspecies

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   extrapolation.  
        2                 DR. REED:  Yes, yes.
        3                 DR. GLANTZ:  I think it would be
        4   clearer to say we don't know what the NOEL is so
        5   we'll take the LOEL, apply a safety factor of some
        6   multiplier, you know, plus the other safety factors
        7   or multiply by the other safety factors rather than
        8   calling it a NOEL.  Because when I see that number I
        9   think it's a piece of data, and it's not.  It's an
       10   assumption.
       11                 DR. SEIBER:  I would argue slightly
       12   differently and say don't throw it out but go study
       13   by study.  If in fact there was a big jump between
       14   where the effect was observed and the next one, then
       15   you've got a problem, just as you pointed out.  
       16                 But if there was a small jump, this is
       17   standard fare in risk assessment, and I don't think
       18   I'd want to throw out all the data that has only
       19   LOELs and not use them at all.  
       20                 DR. FROINES:  I think that you
       21   ultimately are going to have to look at the issue
       22   distributionally and not simply taking these
       23   averages.
       24                 DR. FUCALORO:  John, did you say look
       25   at the issue what?  I missed it.  

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1                 DR. FROINES:  Distributionally.  
        2                 DR. REED:  Right.  
        3                 DR. FROINES:  You want to look and see
        4   how the animals are affected and to what degree
        5   across the range --
        6                 DR. REED:  Right.  But the response
        7   at the LOEL is very important and so that the ideal
        8   case would be to do a benchmark dose approach where
        9   you identify the percentage of response, like 10
       10   percent of response, and instead of extrapolating,
       11   you're sort interpolating it --
       12                 DR. FUCALORO:  But benchmark assumes
       13   dose response -- doesn't it -- data?  Availability
       14   of --
       15                 DR. REED:  Right.  In this case it was
       16   not available.  
       17                 DR. FUCALORO:  Right.  That's what I
       18   mean.  That's the problem.  You don't have --
       19                 DR. REED:  That's the problem, yes. 
       20   Thank you.
       21                 DR. FROINES:  But you're still right
       22   that in -- that I still would argue that the
       23   benchmark approach is the better approach in the long
       24   run and that these historical safety factor
       25   approaches are really in a sense unsatisfactory from

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   a statistical standpoint.  
        2                 DR. REED:  Right.  For many
        3   considerations it's unsatisfactory, yes, you're
        4   right.  
        5                 DR. BYUS:  Isn't there one study that
        6   was used for serum cholinesterase to calculate the
        7   NOEL?  The real NOEL -- calculated NOEL based on
        8   knowing a dose response and knowing an inhibition
        9   serum cholinesterase?  
       10                 And that actually turned out to be
       11   higher.  As I recall, it was a higher value, a real
       12   NOEL, than what she used based on a LOEL to NOEL
       13   factor of 10 conversion.  It was actually higher. 
       14                 DR. REED:  And that was what I was
       15   going to present.  
       16                 DR. BYUS:  I'm sorry.  I just tried
       17   to --
       18                 DR. REED:  It's okay.  
       19                 DR. FROINES:  Did George want to say
       20   something?  
       21                 DR. ALEXEEFF:  Yeah.  I just had one
       22   thing to add to Ruby's comments here, and it's
       23   actually in our acute document so when we get to
       24   that.  
       25                 But there is -- the relationship

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   between the NOEL and the LOEL actually is a
        2   reflection of the steepness of the dose response
        3   curve, so if one has the benchmark dose, you're
        4   taking it into account right off the bat.  
        5                 And we did an analysis which we
        6   referred to in that report that we presented at the
        7   cytotoxicology meetings where we looked at LOELs and
        8   NOELs from over 100 studies, different types of
        9   endpoints, and then did a distributional approach
       10   where -- to look at what -- what percent of the
       11   studies would a factor of 10 be predicting accurately
       12   or better -- or more health protectively.  And it
       13   kind of came out to around 85 percent.  
       14                 And that was sort of what was used to
       15   create this originally in -- or to justify the NOEL
       16   originally in the early '80s or the late '70s.  They
       17   looked at the low -- they looked at what doses caused
       18   the effect and didn't cause it and sort of figured,
       19   well, tenfold protected most of the situations.  And
       20   that's the default that we generally use, and it
       21   seems to be about 85 percent of the results.  But
       22   again, if you use the dose response curve and that's
       23   doing the same thing in the benchmark dose
       24   analysis --
       25                 DR. FUCALORO:  But the dose response

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   essentially gives you those values.  
        2                 DR. ALEXEEFF:  Yes, it's exactly doing
        3   that.  So if you have a shallow dose response, the
        4   other issue to point out is in a situation like this
        5   where you have brain cholinesterase, the dose
        6   response curve will be shallower than if it's
        7   lethality.  Lethality is generally a steeper dose
        8   response curve.  
        9                 So 10 is probably more appropriate or
       10   maybe more appropriate in this case.  We don't have
       11   the data.  But maybe more appropriate in this case
       12   than it would be in the situation like lethalities.
       13                 DR. FROINES:  But we haven't said a
       14   word about metabolism.  We don't know about
       15   nonlinearese yet either.  And there must be some
       16   nonlinearese depending upon the dose.  
       17                 DR. REED:  On the system that maxes out
       18   at the higher dose. 
       19                 In terms of using plasma and RBC
       20   cholinesterase as an endpoint, using the same set of
       21   subchronic toxicity data, the NOEL would be at .3
       22   instead of 0.02 that have been extrapolated from the
       23   NOEL.
       24                 DR. BYUS:  So you're actually choosing
       25   a lower value?  

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1                 DR. REED:  Yeah.  Almost tenfold lower
        2   than --
        3                 DR. FROINES:  I was saying goodbye to
        4   Jim.  What did you say?  I'm sorry.  This is
        5   important.  
        6                 DR. REED:  Using the same set of
        7   database, the subchronic toxicity database, if I were
        8   to pick a NOEL based on plasma and RBC cholinesterase
        9   inhibition, the NOEL would be 0.3 instead of the NOEL
       10   that I estimated from the LOEL.
       11                 DR. FROINES:  You said the LOEL would
       12   be 0.3?  
       13                 DR. REED:  NOEL.  No effect level would
       14   be 0.3.
       15                 DR. FROINES:  With what endpoint? 
       16                 DR. REED:  Plasma and RBC
       17   cholinesterase inhibition. 
       18                 DR. FROINES:  Plasma --
       19                 DR. REED:  And RBC cholinesterase
       20   inhibition.  
       21                 DR. BYUS:  There basically was one
       22   fairly decent study where they actually measured over
       23   quite a large number of doses in animals.  They
       24   actually measured the serum cholinesterase.  
       25                 And if you take that value -- I

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   couldn't figure out why she wasn't taking that value. 
        2   Well, that value turns -- which is a real NOEL, and
        3   essentially you can measure that in the dose below
        4   which you don't get any reduction in serum
        5   cholinesterase, which the EPR doesn't like by policy
        6   to pick for a NOEL because they don't feel it -- I
        7   mean, I'm not -- you know what I mean.  Because I
        8   don't feel it has any function.  
        9                 But it's really not a very good way to
       10   do it.  That dose actually turns out to be
       11   significantly higher than the dose that they chose
       12   based on the tenfold lower than the LOEL. 
       13                 DR. FROINES:  I think the tenure of the
       14   conversation today is I don't see anybody in the room
       15   saying that the blood cholinesterase is not a measure
       16   of some adverse effect.
       17                 DR. BYUS:  I don't either anymore.
       18                 DR. FROINES:  I think that one has
       19   problems with validation of the relationship, but I
       20   think that nobody would argue that it's good for you. 
       21   Nobody -- not even Paul.  That was a joke.
       22                 DR. BYUS:  But the point is --
       23                 DR. GLANTZ:  Paul's boss might.
       24                 DR. BYUS:  She was health conservative
       25   in choosing these values, by my estimation.

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1                 DR. FROINES:  What do you get if you
        2   take the neurobehavioral effect and calculated NOEL? 
        3                 DR. REED:  The neurobehavioral effect
        4   LOEL is .2 milligram per kilogram a day.  And so it's
        5   estimated as 0.02 as the NOEL.
        6                 DR. BYUS:  Which is the lowest value. 
        7   The one she picked is actually based on the neuro --
        8   excuse me.  
        9                 DR. REED:  Yes.  
       10                 DR. BYUS:  As I understand -- I'm just
       11   trying to clarify it in my own mind.  
       12                 DR. REED:  Yes.  
       13                 DR. BYUS:  It's based on the
       14   neurobehavioral effects, but the NOEL is based on the
       15   calculated from the LOEL.  Do you see what I'm
       16   saying?  
       17                 She takes the NOEL tenfold from the
       18   LOEL based on the neurobehavioral effects.  That is
       19   the lowest value of all the data that's out there,
       20   and that's the one she uses to do the
       21   characterization.
       22                 DR. FROINES:  I just want to make sure,
       23   because I'm -- I'm waiting to deal with the -- in
       24   part with neurobehavioral effects as also a chronic
       25   phenomenon and how one does that.  

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1                 DR. REED:  Well, in terms of  chronic
        2   toxicity there is not a neurobehavioral study for
        3   that, and so the lowest NOEL -- Tareq, I'm sorry,
        4   next slide, please.
        5                 DR. FROINES:  Is that because nobody's
        6   looked for any, or is it because --
        7                 DR. REED:  Nobody did chronic
        8   neurobehavior.  It's a long time.
        9                 DR. FROINES:  So it's not a negative
       10   study.  It's a non -- no study.  
       11                 DR. REED:  Correct.  It's no study.  
       12                 In terms of chronic toxicity the NOEL
       13   is 0.02, which you notice is the same as the
       14   subchronic NOEL that I estimated from the subchronic
       15   LOEL.  And the chronic NOEL is based on myelin
       16   degeneration in proximal sciatic and tibial and
       17   peroneal nerves. 
       18                 DR. FROINES:  And there's no evidence
       19   of axonal involvement?  There's no -- you know --
       20                 DR. REED:  No.  
       21                 DR. FROINES:  -- the kind of things you
       22   would see with central neuropathy?  
       23                 DR. REED:  Right.  No.  Not the delayed
       24   neuropathy kind of --
       25                 DR. FROINES:  You don't see any axonal

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   bulging at the nodes?  
        2                 DR. REED:  Yeah.  Not the nodes.  But
        3   in the nerve fibers there's bubbling in the myelin
        4   degeneration, yes.
        5                 DR. FROINES:  So the bubblings is in
        6   the myelin?  
        7                 DR. REED:  Right.  
        8                 DR. FROINES:  And you're not seeing any
        9   axonal effects there?  
       10                 DR. REED:  No, no.
       11                 DR. FROINES:  Like a hexane neuropathy? 
       12                 DR. REED:  Right.  No.  
       13                 Methyl parathion is -- was presented
       14   coexists in the air with methyl parathion.  And since
       15   methyl paraoxon is the active moiety or analogue of
       16   methyl parathion, we thought it's important to look
       17   at the toxicity of methyl paraoxon.  
       18                 In terms of toxicity data all we have
       19   are the acute toxicity data, LD 50 data, and
       20   inhibition dose of 50 percent inhibition of
       21   cholinesterase.  
       22                 In rats it varies from 4.5 to 8.2 in
       23   terms of the ratios between methyl paraoxon and
       24   methyl parathion.  So we have established a toxicity
       25   equivalency factor for methyl paraxon as 10.  

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1                 That would mean methyl paraoxon could
        2   be 10 times more toxic than methyl parathion.  And
        3   that toxicity equivalency factor is used in
        4   calculating the total exposure which includes methyl
        5   parathion and methyl paraoxon.
        6                 And this is where I will stop, and we
        7   will talk about the exposure assessment and then come
        8   back to do risk characterization.
        9                 DR. FROINES:  What time is it?  
       10                 DR. REED:  Five minutes after 3:00.
       11                 MR. GOSSELIN:  Next Tareq Formoli will
       12   present the exposure assessment, and then we'll have
       13   Ruby come back and wrap up, if we have time, putting
       14   the pieces together on the risk assessment.
       15                 DR. GLANTZ:  Just while they're getting
       16   it together.  So we're not acting on this report
       17   today, then?  
       18                 DR. FROINES:  Not even close.  We're
       19   not even really discussing it.
       20                 DR. GLANTZ:  So now, are we going to be
       21   getting another draft of this before we actually
       22   start working on it in earnest?
       23                 MR. GOSSELIN:  Yeah, we have been
       24   working with the leads on this.  Like I said, we have
       25   received public comments during the public comment

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   period including four studies that came in that may
        2   or may not change some of the endpoints and
        3   conclusions, and we need to review that and come
        4   back.  So inevitably this report is going to be
        5   amended.
        6                 DR. FROINES:  If it was said earlier --
        7   and I have forgotten -- Tony and --
        8                 DR. FUCALORO:  Craig.
        9                 DR. FROINES:  -- Craig are the leads.
       10                 DR. FUCALORO:  And a good job we're
       11   doing.  
       12                 DR. BYUS:  We deserve a raise.  
       13                 DR. FROINES:  I just want to comment
       14   from the chair and say I wanted to make sure
       15   everybody realizes what a good job you're doing.
       16                 DR. GLANTZ:  And Bill Lockett will get
       17   them a raise.  You know how the issue of raises comes
       18   up.  
       19                 MR. GOSSELIN:  Even if they did it on
       20   performance, you got it made.
       21                 DR. FUCALORO:  How kind you are.
       22                 DR. BYUS:  They could pay us by the
       23   document, piecework.  
       24                 DR. FROINES:  Let's go.  Please
       25   continue.  

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1                 MR. FORMOLI:  My name is Tareq Formoli,
        2   and I prepared the exposure assessment part of this
        3   methyl parathion document.
        4                 Kevin Kelley already talked about the
        5   products and usage of methyl parathion.  I just would
        6   like to reiterate a few points about the usage that
        7   are relevant to the exposure assessment and the
        8   ambient air monitoring studies that we are going to
        9   discuss later on.  
       10                 Despite the trend that we talked about
       11   that more methyl parathion is used on fruit trees and
       12   vines, 20 to 30 percent of the total use still is
       13   used on rice, and that's based on the use report for
       14   the last five, six years that are available.
       15                 The window of application for rice is
       16   very narrow, and it's applied during the month of
       17   May.  Other uses the season is pretty much it's
       18   applied during the entire year but mostly during the
       19   month of April, May, and June.  Very little is used
       20   during the November and December and January.
       21                 For the last 10 years of illness
       22   reports that is available, there are 18 illnesses
       23   reported for methyl parathion.  Sixteen of those
       24   illnesses were associated with occupational exposure;
       25   two illnesses were associated with non-occupational: 

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   one was an attempted suicide, and one was a drift, 
        2   associated with drift.
        3                 There are several studies of methyl
        4   parathion ambient air monitoring.  The first study
        5   that -- that is the Stanley, et al., study.  They
        6   looked at 10 states including California at Fresno
        7   and Riverside.  They did not detect any methyl
        8   parathion in Fresno and Riverside, but in other
        9   locations the maximum they detected was 148 nanogram
       10   per cubic meter with an average of 29 nanogram per
       11   cubic meter.
       12                 Arthur, et al., we -- in Stoneville,
       13   Mississippi, they observed the maximum level of 2,060
       14   nanogram per cubic meter which was the highest
       15   reported in the literature.
       16                 DR. FUCALORO:  And you'll check that
       17   number; right?  
       18                 MR. FORMOLI:  Yes.
       19                 DR. FUCALORO:  That's the number?  
       20                 MR. GOSSELIN:  Actually, we looked --
       21   if you look at -- Lynn Baker, actually, pointed out
       22   the -- the footnote E actually explains where they
       23   took -- where those numbers actually came from.  
       24                 It had to do with they took weekly
       25   averages versus the monthly averages.  So the numbers

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   are correct, and they're not from the same source of
        2   data.
        3                 DR. FUCALORO:  Okay.  
        4                 MR. FORMOLI:  Kutz, et al., study, they
        5   looked at 15 states.  They did not look in
        6   California.  The levels ranged from non-detectable to
        7   a maximum of 278 nanogram per cubic meter which was
        8   in Oklahoma.  
        9                 Kutz in 1983, they looked at ten
       10   locations in eight states including Pasadena and
       11   Fresno cities.  They actually looked for
       12   p-nitrophenol which is a breakdown of methyl
       13   parathion.  The average was 2.9 nanogram per cubic
       14   meter with a maximum of 160 nanogram per cubic.
       15                 Sava looked at Salinas residential
       16   areas, and only one sample was positive, and that was
       17   17 nanogram per cubic meter.
       18                 The Seiber, et al., study, which was
       19   the most -- the study with the considerable amount of
       20   information, this study conducted -- was conducted in
       21   two counties of Colusa and Sutter which are the rice
       22   growing areas of California.  
       23                 This is 24-hour sampling for four days
       24   throughout the use season of methyl parathion to
       25   rice, and it was from May 12 to June 12.  They looked

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   for methyl parathion and also for methyl paraoxon.  
        2                 The highest level of methyl parathion
        3   was observed in Maxwell, and it was 34.7 nanogram per
        4   cubic meter with an average of 8.4.  The highest
        5   level of methyl paraoxon was 9 nanogram per cubic
        6   meter with an average of 1.8 nanogram per cubic
        7   meter.
        8                 Would you go to the next slide, please.
        9                 Figure 1 shows the use of methyl
       10   parathion around the areas of Maxwell and Williams
       11   during this -- when the study was conducted.  
       12                 As we see, the use starts somewhere
       13   around May 3, and it peaks about May 11 to May 23,
       14   then it drops, and by end of early June it's -- there
       15   is no application.
       16                 And the areas of Sutter County and
       17   around Trowbridge and Robbins the application
       18   started -- you know, there were just some
       19   applications May 2, but there were no applications
       20   until May 18, and then it just lasted for 10 days or
       21   so.
       22                 Next one.  
       23                 Figure 3 shows when we put the
       24   application along with the levels of methyl parathion
       25   in the air in Colusa County.  As we see, the highest

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   levels were observed during the peak application
        2   season with highest levels in the town of Maxwell. 
        3                 Figure 4 also shows the use versus
        4   levels of methyl parathion in the air, as we see, and
        5   Sutter County, it's mostly -- the levels of methyl
        6   parathion were mostly non-detectable except for the
        7   high peak application periods.
        8                 There were also -- we also looked at
        9   several application site air monitoring for methyl
       10   parathion.  The first study, ARB study, they
       11   monitored 80 acres of rice field in Sutter County. 
       12                 They had monitoring stations at
       13   20 yards downwind and 20 yards upwind and at 250
       14   yards -- I believe it was downwind also.  Right after
       15   one hour after the application, they did not detect
       16   any methyl parathion at 250 yards.  
       17                 But at 20 yards the levels are shown in
       18   table 3, and as we see, as time passes, the level of
       19   methyl parathion declines considerably to -- from 512
       20   nanogram per cubic meter at 1 hour after the
       21   application to 28 nanogram per cubic meter at 49 to
       22   73 hours after the application.
       23                 The other study of application site was
       24   by Seiber and McChesney.  They -- the monitoring site
       25   for this study was at 17 yards downwind rice field in

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   Glenn County.  
        2                 Samples were collected at 1, 7, 48, and
        3   55 hours after the application, and the
        4   concentrations were 1,030, 1,160, 51, and 48 nanogram
        5   per cubic meter, respectively.
        6                 The last study was by Jackson and Lewis
        7   in North Carolina.  This is not -- this was not in
        8   California.  They looked at the concentration 1 meter
        9   from the tobacco field.  And there were two fields: 
       10   one was applied with EC formulation, and the other
       11   was applied with microencapsulated formulation. 
       12                 As it was pointed out before, the
       13   levels of methyl parathion were much lower with
       14   the -- when the microencapsulated formulation was
       15   used.
       16                 Next, please.  
       17                 To estimate public exposure to methyl
       18   parathion we divided the humans in three subgroups: 
       19   children of six years old for -- to present children;
       20   adult female; and adult male.  
       21                 Type of exposure was also divided in
       22   three groups:  absorbed daily dosage to represent
       23   acute exposure; seasonal average daily dosage to
       24   represent subacute or seasonal exposure; and annual
       25   average daily dosage to show the annual exposure.

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1                 Acute exposure or absorbed daily dosage
        2   was based on 95th percentile of the concentration of
        3   methyl parathion in the air; seasonal average daily
        4   dosage was based on average of the season; and annual
        5   average daily dosage was based on average of the
        6   season for nine months of the season -- in a year
        7   which is 12 months.
        8                 Based on the Seiber, et al., 1987
        9   study, the estimates of exposure ranged from -- we're
       10   going to look at the location with the highest
       11   concentration of methyl parathion, which was in the
       12   Maxwell, and it ranged from 5.4 nanogram per kilogram
       13   per day for adult female to 21.9 nanogram per
       14   kilogram per day for a child.
       15                 Seasonal average daily dosage ranged
       16   from 1.5 nanogram per kilogram per day for an adult
       17   female to 6.2 nanogram per kilogram per day for a
       18   child.  And annual average daily dosage ranged from
       19   1.2 nanogram per kilogram per day to 4.7 nanogram per
       20   kilogram per day for a child.
       21                 The estimate of exposure from
       22   application site airborne methyl parathion based on
       23   ARB study and also Seiber and McChesney study are
       24   shown on table 6.  
       25                 At 20 yards the estimate of exposure

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   ranged from 39 nanogram per kilogram per day for
        2   adult female to 159 nanogram per kilogram per day for
        3   a child.  At 17 yards the range was approximately 99
        4   nanogram per kilogram per day for an adult female to
        5   360 nanogram per kilogram per day for a child.
        6                 For the ambient air monitoring that
        7   they did look at both methyl parathion and the methyl
        8   paraoxon, and for the application site monitorings
        9   they did not look at the methyl paraoxon.  
       10                 So what we assumed was we looked at the
       11   ratio of methyl parathion to methyl paraoxon that was
       12   observed in the ambient air monitoring study, and we
       13   assumed that that ratio would stand for application
       14   site also.  
       15                 We made some assumptions to come up
       16   with the exposure, and some of these assumptions, we
       17   believe, are conservative assumptions.  We assume
       18   inhalation uptake and absorption of 100 percent.  
       19                 We also assumed DEF indoor
       20   concentration would be as much as outdoor.  And since
       21   the source of ambient air in this case is outdoor and
       22   children and adults spend most of their time indoors,
       23   then we would assume that would probably be a
       24   conservative assumption.
       25                 As far as dermal exposure from the

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   ambient air, we believe that there is potential for
        2   dermal exposure.  However, there are no studies to
        3   monitor that, and we believe that dermal protection
        4   and clothing protection would give adequate
        5   protection that makes this exposure insignificant.
        6                 I think I would end my presentation at
        7   this point.
        8                 MR. GOSSELIN:  We have about ten
        9   minutes, and Ruby said she can get through the final
       10   piece in ten minutes if you wanted to race.
       11                 DR. FROINES:  No, I'd rather not.
       12                 DR. GLANTZ:  No?
       13                 I think it would -- I'd like to at
       14   least maybe get a summary of it.  I think it's
       15   helpful to -- we were going through these reports to
       16   have sort of this overview.
       17                 DR. FROINES:  What time is it now?
       18                 DR. GLANTZ:  It's 20 after 3:00.  
       19                 DR. FROINES:  We can finish it, but I'm
       20   not --
       21                 DR. BYUS:  I'm prepared to stay all
       22   night if necessary.  No, just kidding.
       23                 DR. FUCALORO:  As far as I'm concerned,
       24   you can stay all night.
       25                 DR. GLANTZ:  We're not going to take

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   any action, but it would be helpful to me, having
        2   come this far, to just hear the last bit of it.
        3                 DR. FROINES:  Okay.  I have a reception
        4   I have to be at in UCLA.  
        5                 DR. REED:  I will speed talk.
        6                 DR. FROINES:  No questions, Stan.  
        7                 DR. REED:  I want to start with the
        8   first slide which is a continuation of what Tareq was
        9   presenting.  Just one highlight:  The fact that I'm
       10   only showing data for the highest exposure group
       11   amongst the three exposure age groups that Tareq had
       12   shown, and in this case it's six years old because it
       13   has higher breathing rate per body weight basis.  And
       14   the total exposure would be the exposure of methyl
       15   parathion plus methyl paraoxon's exposure times 10 as
       16   the toxicity equivalency factor.
       17                 DR. FUCALORO:  Just quickly, the
       18   exposure for the paraoxon is roughly 13.5 of the
       19   parathion; is that right?    
       20                 DR. REED:  It's 2.5.
       21                 DR. FUCALORO:  2.5?  
       22                 DR. REED:  Yes.  And then you add one
       23   from methyl parathion, and it becomes 3.5 in total.
       24                 DR. FUCALORO:  Got you.
       25                 DR. FROINES:  And we haven't had any

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   discussion and we won't today but about dermal or
        2   oral uptake.  
        3                 DR. REED:  Correct.  I think Tareq
        4   covered a little bit on the insignificance of dermal
        5   exposure.  But we need to talk about this.  
        6                 DR. GLANTZ:  Just for the record the
        7   chair is asking questions.  I'm sitting quietly.
        8                 DR. FROINES:  But you would not
        9   actually accede to the rules so -- 
       10                 I think that this other issue of
       11   microenvironmental monitoring is one that we haven't
       12   addressed, and I think we need to talk about it in
       13   the future.  
       14                 DR. REED:  All right.  
       15                 So with the table I have in the
       16   transparency for you is the exposures of the six
       17   years old since they're the highest amongst the
       18   three, and I have one column on ambient air exposure,
       19   and the other column is for off-site exposure at 17
       20   yards away from the edge of the field.  And I'm not
       21   reading the numbers now.  
       22                 Next slide, please.
       23                 The risk is characterized by the
       24   calculation of margin of exposure which is NOEL
       25   divided by the exposure.  And again, I've shown you a

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   table in the transparency calculated both based on
        2   human NOELs for the acute seasonal exposures and also
        3   animal estimated NOELs for acute seasonal, and then
        4   chronic NOEL as at 0.02 milligram per kilogram a day.  
        5                 I failed to mention that if I were to
        6   select a chronic NOEL based on cholinesterase
        7   inhibition, then NOEL would be 0.1 milligram per
        8   kilogram a day, about fivefold higher than the NOEL
        9   that I'm using here.
       10                 The off-site exposure is based on
       11   24 hours of exposure, and the margin of exposure is
       12   250 based on human NOELs and 80 based on estimated
       13   NOELs in rats.
       14                 Next slide, please.
       15                 I have just summarized five areas of
       16   uncertainties.  The first one is the uncertainty
       17   surrounding the human NOEL of 0.31.  The strength of
       18   that is that if I were to use human NOEL, then I
       19   don't need the interspecies extrapolation and the
       20   uncertainties associated with it.  
       21                 However, the study -- or this series of
       22   three studies are fairly limited in terms of
       23   observation and reporting.  The endpoint that they
       24   were looking for was just cholinesterase inhibition. 
       25                 And there's only five adults in each

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   group with unspecified body weight, so I have to
        2   assume a body weight of 70 kilograms.  And I was not
        3   quite sure about the NOEL because the LOEL was just
        4   10 percent above the NOEL, and it has a substantial
        5   RBC cholinesterase inhibition.  
        6                 The other concern that I have is that
        7   this is a 30 day NOEL, and when I used it for the
        8   seasonal exposures, which is assumed to be nine
        9   months, I was not sure how adequate it is to address
       10   the nine months of exposure.
       11                 The uncertainties surrounding the acute
       12   subchronic NOELs -- estimated NOELs in rats, of
       13   course, the strength is that the endpoint seemed to
       14   be more sensitive and that LOELs was determined in
       15   multiple studies.  I think there was a total of four
       16   studies.  So that sort of supported each other.
       17                 And I was happy because the
       18   subchronic -- estimated subchronic NOEL comes out at
       19   the same level as the chronic NOEL, and I felt more
       20   comfortable using such a level to address the nine
       21   months of the season of exposure.  
       22                 The weaknesses of course is because
       23   these studies are published in open literature so
       24   there was not a lot of details about this study and
       25   its reporting.  And the measure of uncertainty was

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   because it was estimated from a LOEL.
        2                 Next slide, please.
        3                 The third area of uncertainty is about
        4   the toxicity of methyl parathion.  The data is really
        5   limited only regarding the acute toxicity database. 
        6   And TEF was estimated based on a range of 4.5 to 8.2
        7   and scaled up to 10.  
        8                 There was also an uncertainty
        9   associated with the calculation of total exposure
       10   fractioned into the exposure of methyl paraoxon,
       11   which is assuming that the concentration of methyl
       12   paraoxon in the air is 25 percent of the
       13   concentration of methyl parathion.  And we all know
       14   that a fixed ratio of that just doesn't exist in
       15   time, and so that was another area of uncertainty.
       16                 The fourth area about is exposure
       17   assessment, and I think that Tareq fairly adequately
       18   covered that.  I just highlighted three points. 
       19                 Using default parameters does not
       20   account for the variation in humans, even within the
       21   six years old.  The monitoring data are limited.  And
       22   the off-site exposure, we assume, is at 24 hours at
       23   16 yards away from the edge of the field.  In most
       24   cases it would be probably less than 24 hours unless
       25   you have a farmhouse there, which is a possibility.

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1                 The fifth area of uncertainty is about
        2   the Food Quality Protection Act mandated
        3   consideration of uncertainty factor or the safety
        4   factor of up to 10 to address the possibility of
        5   increased sensitivity or heightened sensitivity in
        6   infants and children or in pre- and postnatal period.  
        7                 And from the database it looks like one
        8   may need to consider an additional uncertainty factor
        9   for the pre and postnatal sensitivity.  And this is
       10   really based at looking at the developmental and
       11   reproductivity toxicity database.  It's covered in
       12   more detail in the document.
       13                 Next slide, please.
       14                 We then calculated the reference
       15   concentration using the NOELs, and the calculated
       16   reference concentration is for 24 hours of exposure,
       17   and the accounted for methyl parathion's
       18   concentration of 25 percent of methyl paraoxon and
       19   TEF of 10 from methyl paraoxon, and uncertainty
       20   factor of 10 is used if I were calculating reference
       21   concentrations from the animal NOELs.  And again,
       22   this is based on exposure parameters of the six year
       23   old.  And so it comes out to be in that table the
       24   acute reference concentration could be as low as 40
       25   PPT and seasonal chronic would be 8 PPT.

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1                 Attention to the -- next slide,
        2   please -- to the transparency is three -- are three
        3   equations, just of a derivation of how the reference
        4   concentration is calculated.  
        5                 Essentially it's a back calculation
        6   from the exposure equation with the exposure being at
        7   reference concentration which is NOEL divided by
        8   desirable margin of exposure.  And then you can back
        9   calculate the concentration.  And this takes into
       10   account again the concentration or the concomitant
       11   presence of methyl paraoxon with methyl parathion.
       12                 That's it.
       13                 DR. GLANTZ:  Could I just ask one
       14   procedural question?  
       15                 DR. REED:  Yes.
       16                 DR. GLANTZ:  How is this going to
       17   proceed now?  When's this going to come back to us
       18   for consideration, formally?  Do you know?  
       19                 DR. FROINES:  Next month.
       20                 DR. GLANTZ:  Next month?  And it will
       21   be the same report with the -- 
       22                 DR. REED:  With the added studies, the
       23   studies that they --
       24                 DR. GLANTZ:  That you handed out?  
       25                 DR. REED:  Yeah.  

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1                 DR. GLANTZ:  Are you going to send us
        2   like another full draft of it or what?  
        3                 MR. GOSSELIN:  Yeah.  What I'll do is
        4   when we complete the review of the studies, we'll
        5   send those sections out so you'll have that separate. 
        6   And then you'll have sort of the full clean report
        7   like you had today.  But you'll have separate sheets
        8   on the description of what those four studies had.
        9                 DR. GLANTZ:  Now -- so are you going to
       10   give us a new -- the question is do I need to take
       11   this home?  Or are you going to give us the new one
       12   that has the changes in it?  
       13                 MR. GOSSELIN:  We are going to give you
       14   the new ones with the changes in it.
       15                 DR. GLANTZ:  Then what I suggest you
       16   do -- and we had OEHHA do this -- is when you put
       17   changes in, do a red-line strike-out version of it so
       18   that the deletions and the additions are obvious. 
       19                 MR. GOSSELIN:  Okay.
       20                 DR. FROINES:  Let's ask a different
       21   question.  When do you think you'll get that to us?  
       22                 MR. GOSSELIN:  I can't say.
       23                 DR. FROINES:  Ballpark.
       24                 MR. GOSSELIN:  We might need to push
       25   this off until the next meeting, then.

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1                 DR. FROINES:  I don't understand.
        2                 MR. GOSSELIN:  They were saying it
        3   might take three to four weeks to complete the final
        4   review of those studies.
        5                 DR. FROINES:  So --
        6                 DR. BYUS:  And actually, I'm not going
        7   to be here, and I'm the lead person on this.  And I'm
        8   not going to be here.  I will not be here for the
        9   next meeting.
       10                 DR. FROINES:  You won't be?
       11                 DR. BYUS:  I won't be.
       12                 DR. FROINES:  So we don't have --
       13   January 15, since we're not having the workshop,
       14   let's just have the meeting because we already know
       15   people are available.  So let's take up methyl
       16   parathion on the January 15th meeting.  
       17                 MR. GOSSELIN:  And we can do a -- we
       18   can make a presentation on molinate.  
       19                 DR. FROINES:  It sounded to me like we
       20   have the workshop, we have George who will go on as
       21   long as you let him, and we have molinate.  So I
       22   don't think we're short of material.
       23                 So Stan, you don't have to carry it
       24   home then.  I was thinking that you should carry --
       25   no -- yeah, that's right.  You should carry it home. 

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   You should carry it home.  Because you should read it
        2   over the next month.
        3                 DR. GLANTZ:  If you could get it to us
        4   a couple of weeks before the meeting, I'd rather read
        5   that.
        6                 MR. GOSSELIN:  If the -- we're going to
        7   bring this back formally again January 15, you'll
        8   have it more than a couple weeks in advance.  But I
        9   would say that if you read that, you will have the
       10   foundation for the changes.
       11                 DR. FROINES:  I have a different view
       12   of this.  My view is that George -- I mean, rather
       13   Stan can take it home if -- doesn't have to take it
       14   home if we can find a recycling box here.  If it's
       15   thrown in the garbage -- this panel has got to have
       16   its recycling act together.
       17                 DR. GLANTZ:  Peter is very efficient. 
       18   Peter, Peter, you'll find a recycling bin; right? 
       19                 MR. MATHEWS:  Right.  I will.  I
       20   promise.  
       21                 DR. FUCALORO:  He won't put that in it.
       22                 DR. FROINES:  And it's in the
       23   transcript, ladies and gentlemen.  
       24                 DR. FUCALORO:  The SRP recycles.  
       25                 DR. FROINES:  Let me say Paul, Ruby,

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   everybody else, thank you very much.  I think this
        2   was a long, sometimes slow session, but I think we
        3   actually accomplished a lot.  
        4                 And as you can tell, we are going
        5   through something of a learning curve ourselves, and
        6   so I think the slowness and the tedious quality, I
        7   think, will change with time, but I think we're
        8   clearly moving in a very good direction at this
        9   point.  And it's very nice to have -- to have a new
       10   document that we say that we've approved.  
       11                 DR. REED:  Yes.  I just wanted to thank
       12   Dr. Byus and Dr. Fucaloro.  Both of you have been
       13   very, very helpful in reviewing the document and
       14   getting back to me and very good interaction.  And I
       15   really enjoyed it.
       16                 DR. BYUS:  Me too.
       17                 DR. FUCALORO:  Yeah, me too.  I thought
       18   we had good discussion.
       19                 DR. FROINES:  Good.  Let's hope this is
       20   the harbinger of the future.  
       21                 Thanks again, everybody.  
       22                           * * *

                BARNEY, UNGERMANN & ASSOCIATES 1-888-326-5900

        1   STATE OF CALIFORNIA    )
                                   )  ss.
        2   COUNTY OF LOS ANGELES  )                                        
        4         I, Katherine Gale, CSR 9793, a Certified
        5   Shorthand Reporter in and for the State of
        6   California, do hereby certify:
        7         That said proceedings was taken before me at
        8   the time and place named therein and was thereafter
        9   reduced to typewriting under my supervision; that
       10   this transcript is a true record of the proceedings
       11   and contains a full, true and correct report of the
       12   proceedings which took place at the time and place
       13   set forth in the caption hereto as shown by my
       14   original stenographic notes.
       15                 I further certify that I have no
       16   interest in the event of the action.
       17                 EXECUTED this 20th day of November,
       18   1998.
       21                            Katherine Gale, CSR #9793