MEETING
BEFORE THE
SCIENTIFIC REVIEW PANEL
OF THE
CALIFORNIA AIR RESOURCES BOARD
SOUTH SAN FRANCISCO CONFERENCE CENTER
255 SOUTH AIRPORT BOULEVARD
SOUTH SAN FRANCISCO, CALIFORNIA
THURSDAY, SEPTEMBER 16, 1999
9:30 A.M.
Vicki L. Ogelvie, C.S.R.
License No. 7871
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
ii
MEMBERS PRESENT
Dr. John Froines, Chairman
Dr. Craig Byus
Dr. Paul Blanc
Dr. Stanton Glanz
Dr. Gary Friedman
Dr. Hanspeter Witschi
Dr. Peter Kennedy
Dr. Roger Atkinson
Others Present:
Bill Lockett, Liaison
Peter Mathews, ARB
Lynn Baker, ARB
Jim Behrmann, ARB
Dr. Ruby Reed, DPR
Paul Gosselin, DPR
Dr. Jay Schreider, DPR
Dr. Melanie Marty, OEHHA
Dr. Andrew Salmon, OEHHA
Dr. John Collins, OEHHA
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
iii
I N D E X
--o0o--
Page
Proceedings 1
Call to Order 1
Opening remarks by Chairman Froines 1
AGENDA ITEMS:
Item 1 - Review report and consideration of
Findings on: The Evaluation of
Methyl Parathion as a Toxic Air
Contaminant 1
Item 2 - Update of projected schedule for
pesticides to be reviewed by the SRP 2
Item 3 - SRP Workshop: Pesticides in the Air
Prioritization of pesticide toxic air
contaminant candidates 21
Reassessment of adult and child
tolerance for pesticidal residue in
food, presentation by Luis Suguiyama 51
Item 4 - Continuation of consideration of draft
report: Air Toxics Hot Spots Program
Risk Assessment Guidelines 85
Afternoon Session 112
Item 5 - Petition for Reconsideration, Diesel
Particulate as a toxic air contaminant 204
Adjournment 205
Certificate of Reporter 206
--o0o--
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
1
1
2 P R O C E E D I N G S
3 --o0o--
4 CHAIRMAN FROINES: I would like to call the meeting
5 to order.
6 We clearly have a quite extended Agenda over the
7 next couple of days.
8 We anticipate completing methyl parathion this
9 morning, and then looking at issues of prioritization, and
10 this is in the context of a little bit of a workshop to look
11 at the issues, and then to look at the first 39 RELs,
12 although there have been some minor changes in that, and
13 Melanie will tell us about that, and then finally tomorrow,
14 we will talk about exposure characterization and monitoring.
15 Why don't we begin with methyl parathion.
16 What we have done, we have gotten comments back
17 from Members of the Panel. The Panel has received --
18 So, Roger Atkinson has made some changes, suggested
19 changes to paragraph 3, and those have been incorporated, and
20 then I sent an E-mail to Craig, and Ruby yesterday, asking
21 for some changes in the document, and that is what Peter is
22 handing out now.
23 What is the best way to deal with this?
24 Ruby, do you want to tell us what those changes
25 are, because nobody is going to be able to read them.
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
2
1 Pesticide Regulations.
2 What I have in terms of showing the changes that I
3 have made is in the strike-out red-line version that Mike is
4 going to show on the transparency.
5 The changes were made in page 6, item 25 and 26, in
6 that now the level of exposure is also included in the
7 findings.
8 In the findings you would have the NOAELs, you
9 would have the margin of exposure and the previous version
10 does not have the exposure, now it has, so in item number 25
11 and 26, in page 7.
12 CHAIRMAN FROINES: Let me just explain to the Panel
13 why we did that.
14 What we had in these findings that we were working,
15 was that we had the NOAELs in the milligram for kilogram day
16 units, and then there were the MOEs that were calculated.
17 No reader could really understand how one goes from
18 the NOAEL to the MOE, because the actual exposure of the
19 monitoring data was not provided and not provided in common
20 units, so one could not easily look at the NOAEL and the
21 monitoring data and do that division and come up with the
22 MOE, and what we are trying to do now is show what the NOAEL
23 is, what the monitoring information, the exposure information
24 is that is being used for the calculations of MOE and then
25 anybody can than divide those two to actually come up with
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
3
1 the MOE.
2 So, it is clearly transparent to any reader who
3 would look at the document.
4 DR. REED: Okay. In page 7, I have made a minor
5 change on the wording, instead of saying subchronic on item
6 number 30, instead of saying subchronic to be consistent with
7 the document, it is seasonal.
8 Page 9, I have made two changes in item 36, a
9 discussion added regarding the additional safety factor that
10 USEPA was using, and that would result -- will relate in
11 lower RFCs as presented in the document.
12 Item number 37 was added in there, and I think, I
13 want to point the corrections on that, instead of paraoxon it
14 should be paraoxonase, in your copy, I think, I have pointed
15 out all the changes, and that was to highlight the need for
16 research in the area of inter-individual variations.
17 CHAIRMAN FROINES: So, those are the changes that
18 occurred literally in the last 24 hours.
19 All the changes were made -- there is nothing new
20 in the findings over that which is in the parent document.
21 Those changes were made for purposes of greater
22 clarification.
23 I had one further question I wanted to raise with
24 you, and that is -- I had it, and then I lost it.
25 We received information on the use of methyl
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
4
1 parathion, and that was three years of recent data.
2 I thought that I had it right in front of me, and I
3 don't have it. I don't know -- maybe I have it right here,
4 but when I looked at the actual data, for example, in 1996,
5 1997 and 1998, '98 you find that there are 20,918 pounds used
6 in Contra Costa County, and that reflects the fourth greatest
7 use.
8 The third greatest use is in Fresno County, which
9 is 21,764. Highest is San Joaquin 29,186. The fifth is
10 Sacramento County, and the second is Tulare County.
11 So, those current usages are somewhat different
12 than what is in our findings. Our findings talk about
13 Colusa, Fresno, Sutter and Tulare, and those are at odds with
14 the data that you provided us in terms of the actual use
15 information.
16 So, it seems to me that we might want to make, we
17 do not have to do it here, we might want to make a small
18 change just so the data that you provided on actual use is
19 consistent with what is SRP finding.
20 DR. REED: Yes, thank you very much. I think, this
21 one, in the current version of the findings, it was up to
22 1995, and the new data should be incorporated in there.
23 CHAIRMAN FROINES: Without turning this into a
24 discussion, I was curious if you could comment on, methyl
25 parathion, for example, in San Joaquin, is used at 9,000
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
5
1 pounds in 1996, 19,000 pounds in 1997 and 29,000 pounds in
2 1998.
3 So, it is a clear increase, and the same thing in
4 Contra Costa County.
5 What is happening?
6 DR. REED: I think I need to defer that.
7 CHAIRMAN FROINES: Let me just say that the other
8 question, since EPA has come out with a ban on methyl
9 parathion, since Paul is sitting there, if you could tell the
10 Panel what the implications of that ban is, because you also
11 gave us information on the types of fruits.
12 So, for example, there is a lot of methyl parathion
13 being used on apples and an enormous about on pears and
14 walnuts.
15 Walnuts, for example, goes from zero to 32,000 in
16 1998, zero in 1996 to 32,000 in 1998, apples go from 7,000 to
17 27,000 in 1998, and pears go from 13,000 to 34,000.
18 So, those all represent very significant changes,
19 and the question is, what are the implications of that
20 vis-a-vis the Food Safety Act decision by EPA?
21 MR. GOSSELIN: The point you raised, and I think,
22 particularly with methyl parathion, when we started the
23 assessment in monitoring, which occurred largely on rice,
24 which at the time was one of the major use categories, as we
25 got this document together and looked at some of the more
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
6
1 current data, it really showed that the use had started to
2 shift away from rice and to a variety of other crops.
3 Those shift in use, particularly from the way we
4 are looking at pesticides and toxic air contaminates, that
5 the use data is going to be critically important as uses
6 change.
7 One of things we've started to do now that we have
8 six and more years of use data, that it does provide some
9 ability to do some trend analysis to see where different
10 pesticides that we have concerns with, to track shifts and
11 use patterns, which do change over time.
12 You just described changes in use on different
13 crops. There is probably a variety of reasons why that is
14 occurring.
15 Some of it may be due to new pest pressure. Some
16 of it may be due to, you know, regulatory action we may take
17 or EPA may take.
18 In 1998, we took action on, as methyl parathion,
19 which is another phosphate, which might have resulted in the
20 shift to methyl parathion. Those are some of the issues we
21 are looking at now.
22 CHAIRMAN FROINES: Let me ask you this, Paul.
23 Our findings and your documents say a majority of
24 methyl parathion use in California is applied to rice fields
25 over a 45-day period, but in this table you provided us with,
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
7
1 there was 15,000 pounds used in 1996 on rice, and 1998 it was
2 down to 6,000 pounds.
3 So, in fact, rice is by no means -- rice is
4 actually a small player in the overall scheme of things and
5 that peaches -- pears rather, turns out to be the big
6 substance, pears, apples, walnuts, and so that is quite
7 different than rice.
8 So, maybe we should change that to reflect that.
9 But the question is, what is the implication of EPA's ban on
10 methyl parathion for those fruits which are now the major
11 users of methyl parathion?
12 MR. GOSSELIN: The action that was taken, back a
13 month or so ago, it was actually a voluntary agreement that
14 EPA reached with the registrant, primarily driven by the risk
15 assessment that EPA has completed.
16 They did remove a lot of uses, a lot of crops on
17 the label and made adjustments to rates, but there are a
18 number of uses remaining, including alfalfa, almonds,
19 walnuts, and others that do show up as fairly significant
20 uses in California.
21 So, there are going to be uses of methyl parathion
22 continuing. They did remove a number of uses off the label,
23 what implications that has for increasing control needs and
24 use of other pesticides and what other subsequent action may
25 occur with methyl parathion, we cannot predict.
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
8
1 CHAIRMAN FROINES: Based on this, the implication
2 is that the amount of methyl parathion on some crops is
3 clearly not only increasing but increasing rather rapidly.
4 Do you foresee the same trend?
5 MR. GOSSELIN: For the foreseeable future, that is
6 really hard to say.
7 The circumstances, behind the numbers, particularly
8 '98 numbers, that was one of the issues when we came out and
9 took some emergency action on methyl -- one of the issues,
10 growers would have to shift to methyl parathion.
11 How much of that was a factor, versus some other
12 management decisions they had to make, we need to look into.
13 But this trend analysis is clearly going to be a major
14 element in how we prioritize and continually to evaluate
15 shifts in uses and shifts in exposure patterns to make sure
16 that the risks that are identified here are adequate and
17 protective.
18 So, all I can say is, yes, this is definitely
19 something that shows the shifts in patterns is something that
20 we are going to have to keep an eye on.
21 CHAIRMAN FROINES: Well, you know, it is an
22 interesting issue, because I complain constantly on the
23 Carcinogen Identification Committee about the tiering of
24 lists that we get ourselves involved in, and here we have the
25 same kinds of problems where we identify compounds as toxic
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
9
1 air contaminants and then becomes -- always been unclear to
2 me what happens after that.
3 It's sort of like everything then drops. We have
4 listed it, and than it drops into a black hole, and we never
5 see what happens from that time forward.
6 So, I think the Panel would be interested in
7 knowing over time what actually happens to protect and
8 control exposures to methyl parathion, especially given these
9 increasing trends in use.
10 MR. GOSSELIN: I think that is a well-stated
11 introduction for the workshop today and tomorrow, because, I
12 think, one of the things that we went back after we started
13 to actually have some documents come through the Panel and
14 actually start to look -- the question is, particularly in
15 light of methyl parathion, which is a nice illustration of
16 shifting use patterns from when we originally went out and
17 monitored and started drafting the report, that is going to
18 be a need for some sort of surveillance tracking, both from
19 changes in use patterns, in use changes and what we
20 originally assessed as exposure scenarios and field exposure
21 data.
22 Instead of just sort of saying it is listed and
23 done, how is this actually going to be built into our
24 continuous exposures?
25 CHAIRMAN FROINES: I do not want to carry this, we
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
10
1 are supposed to be talking about methyl parathion, but I just
2 want to make one comment, which is in -- at one point, there
3 was a suspension of use of Telone, and so in 1991 you have
4 only a thousand pounds used in the entire State, and now it
5 is over a million pounds a year is being used in the State.
6 So, there has been an absolute dramatic increase,
7 going from zero to 1.4 million pounds.
8 So, the obvious question becomes, how do we know,
9 because, Lynn Baker, and we can talk about this tomorrow, how
10 do we know that we are not back to a situation, at least as
11 bad, if not worse than what we saw when we suspended it in
12 the first place?
13 So, where you have these dramatic changes in
14 pesticide use, I think it bears --
15 CHAIRMAN FROINES: Are you suggesting in the
16 earlier comments that there needs to be a modification of the
17 draft document, such that there is a very brief section
18 following the current section 3.3.4, which is a section that
19 says something about parathion use after 1995?
20 I mean there can't be a modification to the
21 findings on comments on data that is not in the document.
22 So, I am at a little bit of a loss, and obviously you do not
23 want it to be continually rewritten to be an never ending
24 process.
25 So, I am just a little curious as to what it is
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
11
1 that you are exactly suggesting.
2 For example, the draft document that we were
3 presented with in the four parts with our findings, is this,
4 it was my impression that this was the final draft.
5 Paul, the only reason this comes up, is because
6 somewhere around the first or second week in September, we
7 got the new data, and we can handle it any way you want.
8 We can simply have a sentence in that document that
9 refers to this new updated information and put this in as
10 appendix -- we can do anything.
11 DR. BLANC: Well, what I think would be the most
12 efficient in terms of a way of handling it, would be, a very
13 brief three or four sentence paragraph following section 3.4,
14 which says that the foregoing data covering, I forgot the
15 period, 1990 to 1995, may not necessarily reflect current
16 trends.
17 The most recent data available suggests that Contra
18 Costa County and, blah, blah, blah county may be the higher
19 use, and summarize in that in one paragraph, and then add a
20 modified number one, such that, first of all, the text of
21 what you say would be slightly different.
22 We are saying the majority.
23 DR. REED: Yes.
24 DR. BLANC: If you use words like has been, or
25 something like that, that would be what I would suggest, but
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
12
1 clearly I do not think we can have findings which differ,
2 which address something that does not appear in the body of
3 the work.
4 CHAIRMAN FROINES: So, you can make those small
5 changes?
6 DR. BLANC: It would also leave you out, even if
7 you were able to put everything that was in currently from
8 your September data, it may change next year.
9 MR. GOSSELIN: We are just -- this is another item
10 we are coming out when we issue the annual use report, we are
11 tracking trends of certain categories.
12 One of the categories are toxic air contaminants.
13 So, it is a category of pesticides we are splitting off and
14 tracking uses, so we can track it from '90 for the
15 foreseeable future, that will be published.
16 DR. GLANTZ: I just have one small editorial
17 suggestion in number seven, because I think the way that it
18 reads is confusing.
19 I think what you ought to say there is methyl
20 parathion inhibits cholinesterase (ChE) by binding to its
21 active sites, inhibition of plasma, red blood cell (RBC) and
22 brain (ChE) are well documented.
23 Yeah, because I think it is unclear, the way it is
24 written. It looks like (ChE) means brain cholinesterase, and
25 I don't think that is what you wanted to say.
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
13
1 So, it would just be before (ChE) you would just
2 add the word cholinesterase, and than put (ChE) in
3 parentheses, and then in the next line, delete cholinesterase
4 and get rid of the parenthesis.
5 DR. BLANC: This comes from reviewing many papers
6 by his post documents over the years.
7 DR. GLANTZ: And your post document.
8 DR. REED: This is an oversight.
9 I am sorry.
10 DR. GLANTZ: Yeah, because it could be misread the
11 way it is.
12 DR. BLANC: I have a question, also, for Paul.
13 Is the format of the document, as it is
14 transmitted, sort of the template for how you see future
15 documents coming to us now?
16 Is this your working model, or does this still
17 reflect the modification of a pre-existing document you are
18 still in flux in terms of --
19 MR. GOSSELIN: Yeah.
20 If I can dust off my memory a little bit, this
21 document was the original standard document that we started
22 working with, consistent what we have and the ARB presents,
23 and I think we have gone back to trying to have the documents
24 be consistent with the format of the documents used the same.
25 So, I think the answer is, yes.
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
14
1 DR. BLANC: Okay.
2 I assumed so, but I just wanted to clarify that.
3 CHAIRMAN FROINES: I have maybe half a dozen
4 trivial changes, which I will just give you.
5 They are not worth mentioning. I just have one
6 minor question.
7 You said, upon absorption, in 6, methyl parathion
8 is metabolically activated to methyl paraoxon.
9 Detoxification involved dealkylation and
10 dearylation and elimination as p-nitrophenol in the urine as
11 the leaving group, but you do not mention the other half, the
12 non-leaving group.
13 What happens to it?
14 DR. REED: I would go ahead and add a description
15 of that.
16 CHAIRMAN FROINES: Just a word.
17 Okay. So, I think, unless there are other
18 comments?
19 DR. GLANTZ: I move, we adopt the report of
20 findings, including the changes that were just discussed.
21 DR. BLANC: Second.
22 CHAIRMAN FROINES: Discussion?
23 DR. BLANC: Discussion?
24 Are you going to then circulate a final, final
25 version for us to sign off on and send a fax back or
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
15
1 something like that?
2 CHAIRMAN FROINES: Sure. But I think at this point
3 any further hesitation would cause Craig Byus to jump off the
4 Golden Gate Bridge.
5 DR. FRIEDMAN: When you circulate these revisions,
6 could you please highlight the changes?
7 DR. GLANTZ: Actually, I would rather not circulate
8 the revisions, I am willing to trust the Chair on behalf of
9 the Panel, the permanent Chair now, no longer acting Chair,
10 to just make sure that it was done consistent with the
11 reading, I mean these were very small changes in addition to
12 the one's we just saw, I don't think it is worth circulating.
13 I would hate for Craig to jump off the bridge. So,
14 would that be okay with you, Paul, to just leave it to the
15 Chair?
16 CHAIRMAN FROINES: We will send you, you cannot get
17 away with that, Stan.
18 You will get the final version.
19 DR. GLANTZ: Never mind.
20 DR. FRIEDMAN: Would you highlight the changes,
21 because that would help us a lot?
22 DR. REED: Would you like me to send you an
23 electronic file that has the strike-out and the red-line
24 version, just like I found today?
25 DR. FRIEDMAN: With the changes made?
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
16
1 DR. GLANTZ: Call the question.
2 CHAIRMAN FROINES: All those in favor, aye.
3 I think we owe a debt of thanks, seriously, to
4 Craig Byus, for the effort on --
5 DR. BYUS: I was going to add working with Dr.
6 Reed was a pleasure.
7 It was quite enjoyable. It got a little nerve
8 racking at times, not because of her, but an outstanding job
9 on this document, and I will be glad to work with her in the
10 future on any documents.
11 DR. GLANTZ: Good.
12 You can have all the rest of them.
13 CHAIRMAN FROINES: You have just been assigned a
14 permanent job.
15 So, the next item on the Agenda is the Updated
16 Project Schedule for Pesticides to be reviewed by the SRP,
17 DPR staff.
18 So, Paul, if you and whoever.
19 DR. GLANTZ: Didn't we just decide that they go to
20 Byus?
21 MR. GOSSELIN: Thank you.
22 We, I believe, a memo was circulated on the
23 proposed schedule.
24 For the upcoming year, what we did is, staff went
25 back and took a look at, realistic look at the legal time
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
17
1 frames we have to do public comment, some realistic time
2 frames to be able to respond to those comments, the
3 continuous interaction with SRP leads on the document, the
4 time to bring revised documents to the Panel and have some
5 discussion, and then, kind of map out a time frame with key
6 points to make sure that we at least have a consistent plan
7 ahead for the next year on how to process these documents,
8 actually, for ourselves, also, so we can make sure that we
9 give adequate time to comment and adequate notice to everyone
10 on this.
11 So, that is essentially what we forwarded off last
12 month with the schedule for MITC, mesamolinate and
13 naphthalene.
14 DR. GLANTZ: Paul, as I look at this last memo you
15 sent, you have things that are AB 1807 and SB 950.
16 Do we get all of those or just the AB 1807 one's?
17 MR. GOSSELIN: This will kind of get into
18 prioritization and sort of our risk assessment discussion,
19 but the 1807 document is formatted specifically for 1807.
20 It includes essentially all the same toxin
21 information. The hazard ID section is essentially the same.
22 The only thing logically missing out of it is
23 dietary risk assessment portion and the occupational
24 assessment portion, then the risk characterization and
25 exposures focused solely on ambient air exposures.
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
18
1 Essentially the toxic information is the exact same
2 document.
3 DR. GLANTZ: That was not the question.
4 I was asking a slightly different question. Are we
5 going to be reviewing all of these documents or just the
6 one's that you list as 1807?
7 MR. GOSSELIN: Just the 1807.
8 I will note that the review and the Panel's review,
9 for our 1807, we do use as the external review requirements
10 for our broader risk assessments.
11 CHAIRMAN FROINES: All right. I had one question
12 about this letter that you sent me, dated, August 12, that
13 gives the four compounds and the time frame associated with
14 the MITC document, which I have not looked at.
15 Is that document going to address methyl sodium as
16 well?
17 MR. GOSSELIN: The ambient air exposure issues from
18 that, methyl sodium, converts virtually, readily and
19 immediately to MITC, the methyl sodium, and right now staff
20 is bridging the two.
21 My understanding is principally driven by
22 occupational exposures, the ambient exposures from methyl
23 sodium use are MITC exposures.
24 So, maybe the answer is the MITC exposures that are
25 resulting from methyl sodium use in the 1807 documents, is
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
19
1 that your question?
2 CHAIRMAN FROINES: Well, it is an answer to my
3 question, but I'm not sure it is the answer.
4 How do you, and this is not the place to start
5 discussing the document, that is really a procedural issue.
6 How do you, for example, calculate the MOEs? Do
7 you take data from methyl sodium use and calculate the MITC?
8 MR. GOSSELIN: There is monitoring data of MITC
9 resulting from the methyl sodium use, and there is also
10 modeling and typical range of data from other sort of
11 fumigants.
12 DR. BLANC: I think what you are saying, Paul, is
13 there is virtually no other source for MITC other than methyl
14 sodium, is that what he is saying?
15 MR. GOSSELIN: Yes.
16 Staff said just that the methyl sodium risk
17 assessment will be coming forward to accompany the MITC risk
18 assessments, but principally the pesticidal source for MITC
19 is methyl sodium products.
20 DR. BLANC: So, perhaps the way to package that
21 particular risk assessment would be titling it methyl sodium
22 and MITC.
23 I mean, really we are dealing with the same issue
24 in one of the other pesticides where the breakdown product is
25 a significant issue.
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
20
1 CHAIRMAN FROINES: But, see, I do not know all the
2 different in's and out's of MITC, and Roger may want to ask a
3 question, are there atmospheric chemistry products as methyl
4 sodium differs from MITC, how does all that happen in the
5 atmosphere, and I honestly do not know this.
6 So, it is just a question.
7 We do not want to be -- if we have one compound and
8 it ends up being another compound, we should still be looking
9 at the whole picture.
10 DR. ATKINSON: Basically, the portion that I saw in
11 the environmental was that way when I sent my comments in, I
12 guess that is ongoing.
13 CHAIRMAN FROINES: So, this list of compounds is, I
14 think, we should proceed to the discussion of setting
15 priorities, and these will probably come up again.
16 I will tell you why they will come up again,
17 because we have a 1996 document, and there is the table of
18 pesticides ranked for monitoring, based on your priorities
19 system.
20 Methyl sodium is listed as the third highest
21 priority, and Telone is 14, and azinphos-methyl is 23, and
22 naled is 28, and so a very obvious question is, why are we
23 getting 3, 14, 23 and 28, and whatever happened to 1 and 2,
24 seems a logical question, would be that one would take the
25 highest priority substance.
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
21
1 But why don't we defer that and not put you on the
2 spot, until later, and talk about your part.
3 Why don't you go ahead with the presentation on
4 prioritizations?
5 MR. GOSSELIN: So, that would be under the
6 Workshop, Pesticides in the Air, Pesticide Toxic Air
7 Contaminant Candidate Prioritization.
8 Actually, I think that document is somewhat of a
9 good place to start, but not going back totally and
10 revisiting history, back prior to us actually bringing
11 documents through the process, and I think what was just done
12 previously with methyl parathion and the work that went into
13 that completed, I think, kind of over shadowed somewhat what
14 the 96-2 report was intended for.
15 At the time we were still somewhat struggling with
16 how we were going to link up what we call our 950 risk
17 assessments and the 1807 risk assessments process, and you
18 know that at that time it was not a very smooth period.
19 One of the attempts we made was to try to come up
20 with a different type of ranking system for both monitoring
21 and risk assessment.
22 This was actually an innovative way to give some
23 relative ranking to pesticides next to each other. One of
24 the things, looking back at it, it does try to incorporate
25 use exposure and toxic data and give different weights to
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
22
1 each one to give that relative ranking.
2 What I am going to do is turn over to Dr. Jay
3 Schrieder, sort of our prioritization of doing a 950 risk
4 assessments, which does have an element of trying to track
5 the higher use materials, but it is principally focused in on
6 toxicity.
7 So, probably the short answer is that I think that
8 the value, knowing where we are now and actually having, I
9 think, a pretty solid work plan with deliverable products
10 coming through, that we do need to take a look at this
11 exercise in the 96-2 report.
12 It is sort of a relative ranking list. If you go
13 down to the range, you are talking about total scores of 21
14 to 14 or 15.
15 Given the other parameters, there largely isn't
16 a -- even though the quantity of numbers are there, the
17 quality of distinction between those being top priority risk
18 assessments and for toxic air contaminant may not be that
19 great.
20 CHAIRMAN FROINES: I do not think anybody
21 understands what you just said.
22 MR. GOSSELIN: Maybe the short answer is, that I
23 think that now that we have bridged our main risk assessments
24 with the toxic air contaminant document process, we are still
25 going to capture the one's on the top of this relative
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
23
1 ranking list, and those are going to be the one's that are
2 principally driven by toxicity.
3 The uses are going to change. What this
4 incorporates is some assessment in judgment, a snapshot in
5 time, what we sort of guess upon exposure, based upon use and
6 some environmental parameters, that will change over time.
7 Sort of the system that we have now is still going
8 to bring the pesticides that do have the potential to get
9 into air but pose probably the higher end health risks
10 through the process.
11 DR. GLANTZ: Well, is it, as proposed in earlier
12 discussion that we had about changing uses of methyl
13 parathion, I mean, would it be worth redoing this exercise
14 with the more recent sales data than in the '90 to '94,
15 assuming that the rest of the stuff, the toxicity information
16 has not changed very much, would that be a useful exercise?
17 I do not want to make useless work for you, but I
18 mean, the change in uses that you just talked about earlier
19 were pretty impressive.
20 One thing that is a little concerning about what
21 you said, and we went through this with ARB a long time ago,
22 is, if something is hideously toxic and not used in
23 California, there is no reason to bother.
24 So, I do think we want to take usage into account.
25 On the other hand, if something is not toxic and they use a
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
24
1 lot of it, we do not care.
2 But the other, the last four columns in your Table
3 4 probably are not going to change much since you wrote this
4 report, but the sales use data is now five to ten years old.
5 Would it be possible just to revise that one column
6 and then redo the ranking without spending huge amounts of
7 efforts?
8 MR. GOSSELIN: Yes.
9 That would not take a huge amount of effort.
10 DR. GLANTZ: Do you think it would make any
11 difference?
12 MR. GOSSELIN: It would still be interesting, but I
13 still think it would probably not be inconsistent with sort
14 of where we are going now to eventually capture the materials
15 that are 1 through 30 or 40.
16 It is a matter of which one's can we reasonably
17 package up and get the assessments done in shorter order.
18 The other side of this that factored into the
19 schedule is, we had issues of what monitoring data we had
20 reasonably ready, and also how far along staff were in
21 completing some of these assessments that had been in some
22 cases in the works for a number of years, some of it was a
23 matter of efficiency on what we could actually bring closure
24 to and get the assessments done, given that all of these have
25 some level of concern within some need to have assessments
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
25
1 done on them, again, with methyl parathion and other uses, to
2 maybe overstate or understate what we currently know about
3 the use today, and what the trend has been over the last six
4 years will not reflect what is going to happen tomorrow.
5 CHAIRMAN FROINES: Stan's point is well taken in
6 the sense that the irony is that we do not base any
7 decisions, that we don't base any decisions in the ARB
8 process on exposure issues.
9 If there is exposure, there is exposure. That does
10 not factor into the decision making. Whereas with
11 pesticides, the primary criteria for determining whether a
12 substance is a toxic air contaminant is precisely anticipated
13 exposures.
14 So, the exposure issue becomes one of the central
15 defining features for designations for TAC. To diminish its
16 importance is a mistake.
17 DR. GLANTZ: Although, I think, there is a
18 distinction between exposure.
19 The question of identifying something as TAC and
20 the question of prioritization, because in the ARB process
21 exposure was an important element of the prioritization
22 process.
23 MR. GOSSELIN: Maybe, if Jay begins his
24 presentation, our prioritization for risk assessments does
25 take into account the amount of use, among other things.
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
26
1 So, between these two lists, you won't see that
2 much distinction.
3 The only sort of downgrading or putting into
4 context is putting too much weight on the quantification that
5 is in the 96-2 report versus what it generally paints as
6 qualitatively of higher priority materials that need to be
7 evaluated.
8 MR. SCHREIDER: Okay.
9 I will talk about the prioritization under SB 950,
10 and before I get quite into the prioritization, maybe I will
11 give a little bit of background regarding SB 950 and its
12 relative mandates.
13 The handout that you are all given, sort of a
14 schematic of the risk assessments process under SB 950, it is
15 actually called the Birth Defect Prevention Act of 1984 and
16 required the review of the, quote, Mandatory Health Effects
17 Studies that support the registration of pesticide active
18 ingredients.
19 The Act mandated the review of complete studies and
20 also specifically defined Mandatory Health Effects Studies
21 and define these as oncogenicity studies, chronic toxicity,
22 reproductive toxicity, developmental toxicity, geno toxicity,
23 and neuro toxicity.
24 The studies, themselves, were required to be
25 reviewed for completeness and validity first, and if there
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
27
1 was a problem with the conduct of the study, then there was a
2 data gap to clear it, and the new studies had to be
3 conducted, the study review was also to identify any possible
4 adverse health effects, and if adverse health effects were
5 identified, the Department was to determine if those adverse
6 health effects were, quote, significant.
7 Those that decided to make this determination
8 through the risk assessment process.
9 While not specifically addressed by SB 950, there
10 was an obvious need to prioritize chemicals for risk
11 assessment, both, one, just to manage the process was at that
12 point 800 active ingredients and to ensure that the risk
13 assessments were first conducted on the chemicals with
14 highest concern.
15 To do that, DPR formed the affects advisory panel
16 to have accomplished the prioritization, and in that handout,
17 the second memo, which is the third document in the handout,
18 I apologize for the stapling, describes a little bit of that
19 process.
20 The Panel consisted of scientists of both OEHHA and
21 the medical toxicologists, Work and Health Safety Branches in
22 DPR, and that group meets periodically.
23 The process is really somewhat subjective in
24 offerings of consensus objective.
25 CHAIRMAN FROINES: I do not know what documents
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
28
1 that you referred to.
2 DR. BLANC: Talking about the four-page handout,
3 has Memorandum, January 23, Prioritization Process for Risk
4 Characterization for Active Ingredients.
5 Is that correct?
6 MR. SCHREIDER: Correct.
7 The criteria considered, although not in the
8 quantitative fashion, include the nature of the adverse
9 effect, the number of potential adverse effects, the number
10 of species effected, the level of the NOAEL and then
11 potential human exposure, the different use patterns, the
12 quantity used and also the quantity applied, given an
13 application, and in addition, USEPA actions, and other
14 considerations that may come up specific to the pesticide.
15 Pesticides were then assigned priority of high,
16 moderate or low, and this priority listing is updated
17 periodically and presented in formal report to the
18 Department's Pesticide Registration and Evaluation Committee.
19 I think, approximately 40 or 39 sector reports have
20 been put out, listed in prioritization. So that changes,
21 when we get new active ingredients, when there are new
22 studies that come in, there may be additions to that
23 prioritization list.
24 The initiation then of the risk characterization
25 document is addressed, particularly by the second memo in the
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
29
1 handout. In that process, the branch chiefs and senior
2 toxicologists from the Work and Health Safety of Medical
3 Toxicology Branches and determine which high priority risk
4 assessments to initiate first.
5 Some of those same factors considered for
6 prioritization play a role in that decision, as well as
7 management needs, actions by other agencies, requests from
8 other agencies, public interests, anticipated additional
9 uses, such as in an eradication program, such as the red fire
10 ants, the report of red fire ants, and in some cases a
11 chemical of moderate priority could move up based on those
12 new uses.
13 An example of that would be hydro methionyl or
14 andro, which has seen with decreased use but may become a
15 chemical of choice for use of treatment of the imported red
16 fire ant. So that may move up the importance of the
17 chemical.
18 At this point, it might be useful to talk a little
19 bit about the toxicology data that is considered. While the
20 Act itself was fairly specific in outlining in the, quote,
21 Mandatory Health Effect Studies, and those studies start the
22 process that form the basis for initiating our risk
23 assessment, once that risk assessment has been initiated, all
24 relevant data and studies are considered.
25 This includes acute and subchronic studies that are
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
30
1 on file but were not part of Mandatory Health Effect Studies.
2 These, in fact, often have turned out to be drivers in the
3 risk assessment, and these also may include studies in the
4 open literature, with the caveat that there has to be enough
5 information present to adequately review the study, at least
6 from the standpoint of the act of requiring the use valid and
7 complete and adequate studies.
8 A little bit also about peer review. When the risk
9 characterization document is completed and undergoes internal
10 scientific peer review and is then sent to USEPA and OEHHA
11 for their review and comment.
12 At this point now, the new laws that may undergo
13 additional external peer review, that is, there is now a
14 requirement that if there is a scientific basis for our
15 regulation, that scientific basis has to undergo external
16 peer review, either by the National Academy of Scientists or
17 by scientists in the University of California system or
18 okayed by the University of California system, and clearly
19 this Panel would fit the criteria or meet the spirit of
20 external peer review.
21 The other thing that should be pointed out, is that
22 in some cases if a pesticide has significant food use, the
23 Department may conduct a separate dietary risk assessment to
24 meet the requirements of food safety mandates.
25 That risk assessment could then be expanded when
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
31
1 occupational and residential exposure became available.
2 As you noted, there is a commitment for the
3 documents to be submitted this year for azinphos-methyl,
4 ethephon, MITC, malonate, maleic.
5 We have already spoken to the prioritization that
6 they would have had from the 1996 document. Also, I would
7 like to briefly mention the recent review of the risk
8 assessment process under Cal EPA itself.
9 There was a review that was concluded in 1996,
10 where all of the risk assessment processes of the Board's
11 Department and Offices of Cal EPA were reviewed and were
12 culminated in fairly extensive formal report in October of
13 1996.
14 The Risk Assessment Advisory Committee, or RACE,
15 made a number of recommendations, and a few are relevant to
16 today's discussion.
17 Primary, our main recommendation was that the level
18 of effort on the risk assessment should be commensurate with
19 the importance of the risk assessment. I think this is a
20 fundamental to the whole purpose of prioritization.
21 There is not a whole lot of point in doing a risk
22 assessment on something that is relatively non toxic or maybe
23 toxic but for which there is not much exposure as used in
24 bait box.
25 External scientific peer review was also strongly
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
32
1 recommended, and I have also briefly touched on that. It
2 was also recommended several times that both DPR and USEPA
3 make the best use of scarce resources and avoid duplication
4 of effort by utilizing each others work products.
5 To some extent that factors into our
6 prioritization. If we know EPA is nearing completion of a
7 reregistration eligibility document, or their form of a risk
8 assessment, and is nearing final action, that may be a reason
9 not to initiate and expend a lot of resources on that
10 chemical.
11 I think that ends my description of our
12 prioritization under 950.
13 MR. GOSSELIN: As Jay described, the number of the
14 risk assessments that we have had, sort of initiated upward
15 some over ten years ago.
16 It has been a continuous effort to use the best
17 science available which, as we all know, is continually
18 changing.
19 One of the things that the last couple of years
20 that we made a decision was to try to bring closure to the
21 risk assessments based upon the data we have and to start
22 initiating regulatory decisions based upon the assessments.
23 So, over the last two years or so, out of the some
24 odd, I think, 18 assessments that we had done, 7 of them we
25 have done in the last two years.
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
33
1 We made a commitment to the Legislature to complete
2 out of the priority list of 200 active ingredients, 45 in the
3 next year or so. So, we are somewhat on an accelerated
4 schedule to, one, bring closure to the assessments that staff
5 has been working on over the last number of years, which is
6 also going to provide the 1807 documents that you will be
7 seeing shortly.
8 Some of this because we are still in a transition,
9 that we have had some of these assessments ongoing under the
10 950 process, and then we have had monitoring reports and
11 documents from the Air Board.
12 It is a matter of bridging the two to make sure we
13 can -- the documents that can be prepared, are prepared in
14 short order.
15 The one's that we are initiating now, there is a
16 linkage now between what we are requesting monitoring data
17 for and the initiation of general risk assessments. So, the
18 process is far more seamless than it has been in the past.
19 The other thing that, I think, is going to be far
20 more helpful, is the process that Jay described and our
21 process of initiating risk assessments and the list of
22 pesticides in our risk assessment needs to become more
23 public.
24 One of the things that we are building is a
25 Website, so people can do some searching in a list and some
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
34
1 links to actually have access to the documents that are
2 completed, actually know the time frame that we are looking
3 at to complete certain documents, including 1807 documents,
4 and also, I think, one of the things that is important is
5 that through this prioritization process, we are going to
6 have to try to build in some sort of more open public
7 discussion on how we actually make decisions on initiating
8 risk assessments in a more public and open way.
9 Clearly, right now, there is work that has been
10 sort of built up over the years that needs to be wrapped up.
11 DR. BLANC: Let me see if I understand this
12 correctly then.
13 Basically, in a nutshell, what you have said, is
14 that there is a Committee that meets that includes people
15 from your agency and from related agencies, which is a
16 standing Committee which meets and then comes to agreement on
17 priority chemicals for entering into this process.
18 MR. SCHREIDER: Correct.
19 That would be our Department and the Office of
20 Environmental Health Hazard Assessment.
21 MR. GOSSELIN: It is principally the senior
22 scientists?
23 DR. BLANC: Right.
24 I think, what you have not said, and perhaps this
25 in a later presentation, is -- you have described the process
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
35
1 as somewhat subjective, but I'm sure that does a disservice
2 to the process.
3 What are the actual criteria that are used?
4 Are they the same that are represented in Table 4?
5 Or are there elements to that process that you have
6 not highlighted?
7 CHAIRMAN FROINES: I think that when we established
8 this particular session that what we wanted was a much more
9 detailed description of what you do and the results of what
10 you have been doing.
11 I do not think that this verbal presentation is
12 sufficient.
13 DR. BLANC: Let me hear the answer.
14 Maybe this will help.
15 MR. SCHREIDER: The criteria that are considered,
16 and those are the one's that I have listed, and they are not
17 used in a quantitative fashion.
18 That is why I said it was a subjective decision of
19 the senior scientists, looking at what is the level of
20 toxicity, how is the material being used and placing that
21 into high medium or low priority, and that report is then
22 presented to, in a report form, to the Pesticide Registration
23 Evaluation Committee, listing the additions or deletions from
24 the prioritization list.
25 DR. BLANC: So, each time one of these --
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
36
1 You said there were 25 reports over the last 5
2 years or so --
3 CHAIRMAN FROINES: 40 --
4 DR. BLANC: Okay, 40 reports.
5 So, each time everything appears on it, but may
6 have been placed, or does the supplemental report only
7 highlight things which have changed this year?
8 MR. SCHREIDER: The list itself comes out in each
9 report, but the additions or deletions are highlighted.
10 DR. BLANC: Could we have a copy of the most recent
11 report?
12 MR. SCHREIDER: Sure.
13 CHAIRMAN FROINES: Do you have an overhead of that
14 now?
15 MR. SCHREIDER: No.
16 But I will send a copy of the report.
17 CHAIRMAN FROINES: Wait a second.
18 I am going to be very short tempered very quickly
19 here.
20 We did not anticipate that you would not present to
21 us what you have. A verbal description of which you have
22 done does not meet the goals and objectives of this session.
23 I want to see what you are doing. I want to see
24 the results of what you have been doing.
25 You have 40 risk assessments. You have a process
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
37
1 which you are not following from 1996. There are lots of
2 problems.
3 I want to see what it is, what the 40 risk
4 assessments have been and where you have come in terms of
5 ranking and how you got there.
6 Was this not made clear to you?
7 MR. GOSSELIN: Obviously not.
8 What I could suggest is we table this and bring it
9 up --
10 CHAIRMAN FROINES: We have been planning this,
11 Paul, for over three months.
12 It has never been ambiguous.
13 DR. BLANC: Well, I have a procedural suggestion,
14 actually.
15 We are lucky because we have a two-day schedule.
16 So, what I would suggest is that we sort of break off your
17 presentation now, and then we have some flexibility so that
18 tomorrow or this afternoon -- I'm sure you have easy fax
19 access to the most recent list and show us either around the
20 table or with an overhead so that we can see that, that would
21 be a useful, concrete way of going over what your priorities
22 are, what is in the highest, middle and low group.
23 Because, clearly, we need to see whether that is
24 consistent -- for example, let me just give you some specific
25 questions that will probably come up.
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
38
1 If the memo of June 23, which lists a group of
2 materials which would be the one's most likely to come to us
3 for review over the coming two years, let's say, if there are
4 other materials which appear in your high priority group and
5 also have a high ranking in terms of their ability to get
6 into the air that do not appear here, then we would probably
7 want to focus on what the thinking is specifically in
8 relationship to those.
9 I would imagine that would be the most useful way
10 of doing that.
11 MR. GOSSELIN: I think, going and getting that, the
12 latest report and looking at the list of 45 risk assessments
13 that we have underway, either completed or due to be
14 completed, are largely going to capture -- and out of the
15 first 20, because I was actually thinking of that, the one,
16 number 6 -- number 9, phorate, and number 11, chloropicrin,
17 which is not totally negated, but out of the top 20, all but
18 those two are right now in --
19 CHAIRMAN FROINES: In what?
20 In this list?
21 MR. GOSSELIN: Yes.
22 Are under risk assessment and slated for completion
23 in short order. Then we coupled with monitoring data and
24 what we would is concurrently prepare 1807 documents.
25 DR. BLANC: Right. Then I guess the other question
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
39
1 that will be useful for that discussion would be to make sure
2 all of the one's that you do have risk assessments for, which
3 of those is there active monitoring going on, so we can sort
4 of link that to the discussion with the air monitoring
5 people.
6 Because it will be very frustrating, obviously, to
7 get a document coming to us that has the toxicology
8 evaluation component but was very weak in the air monitoring
9 and then to mandate going out.
10 CHAIRMAN FROINES: I'm confused.
11 Are you saying that you have risk assessments for
12 all 20, for the top 20 of the chemicals on this list?
13 MR. GOSSELIN: I would say all -- except for 3, all
14 the way down to 23, either in progress or have been
15 completed.
16 CHAIRMAN FROINES: The risk assessments?
17 MR. GOSSELIN: Yes.
18 CHAIRMAN FROINES: Okay.
19 So, you have done risk assessments on -- actually,
20 you have said 40 compounds.
21 MR. GOSSELIN: They are proposing.
22 DR. BLANC: They are proposed.
23 They are not all completed.
24 CHAIRMAN FROINES: Right.
25 They are proposed or completed.
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
40
1 You have completed risk assessments on 23; is that
2 what you are saying?
3 MR. GOSSELIN: Yes, somewhere around that.
4 CHAIRMAN FROINES: How do you then prioritize those
5 23 for further action?
6 MR. GOSSELIN: Regulatory action or --
7 Once the -- yes, once the risk assessment is
8 completed, and actually upon completion, one of the processes
9 we have is the Unit puts forward the unacceptable exposures
10 that needs some further restrictions, and those are managed
11 upon completion of the documents.
12 So, we try to make sure there is no lag time
13 between risk management decisions and completing the
14 document.
15 CHAIRMAN FROINES: No, I am talking about the
16 development of 1807 document.
17 MR. GOSSELIN: Okay.
18 Again, this went back -- we went back the last two
19 and a half years ago and tried to do sort of a match of what
20 we had under risk assessment, the list we had of monitoring
21 data in and tried to match up, similar to what you were
22 talking about, what was at a point that we could start
23 bringing documents together for 1807, which is somewhat
24 reflective of the current schedule that we have for the next
25 upcoming year.
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
41
1 For the one's we had assessments underway and
2 ongoing but we didn't have monitoring data, those were
3 factored into the priorities for monitoring.
4 Then, now for the one's that we are starting from
5 scratch, those are linked in with monitoring recommendations
6 to ARB.
7 CHAIRMAN FROINES: But, Lynn, of the 23 documents
8 on the list, do you have it there?
9 How many of them are you doing monitoring on?
10 MR. BAKER: Lynn Baker, Air Resources Board.
11 We have done monitoring for most of these on this
12 list, Dr. Froines.
13 For propargite, an initial report was completed a
14 year or two ago. We did some additional monitoring this
15 year.
16 Chlorothalonil is completed. MITC is completed. I
17 am just going down the list of the top 23.
18 DEF is completed. Endosulfan is completed.
19 We have never been requested to do monitoring for
20 p-Dichlorobenzene.
21 We were initially requested to do monitoring for
22 cyanzine, and then that request was withdrawn.
23 Then the use was -- this was the last year of use.
24 CHAIRMAN FROINES: Can you prepare a list, take a
25 list of 23 that he is talking about, and prepare a document,
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
42
1 a one-page document, that shows the status of each compound.
2 MR. BAKER: Of these 23?
3 CHAIRMAN FROINES: Yes.
4 The other issue that comes up, goes back to methyl
5 parathion question this morning, when we look at the '96
6 through '98 data on methyl parathion, we see rather dramatic
7 changes over what was said in the original document in terms
8 of its being used on rice.
9 So, one of the questions is, since the ball game
10 seems to change, since we are looking at walnuts, almonds,
11 pears on methyl parathion instead of rice, one of the key
12 questions, and dramatic increases in use, the obvious
13 question, I guess, we will come back and talk about this
14 tomorrow, but the obvious question is how do we actually
15 identify the most important uses at the time you are doing
16 the monitoring?
17 Because, again, it would not be appropriate to be
18 out doing rice at a few thousand pounds when you have 34,000
19 pounds in pears from methyl parathion. So that, obviously,
20 how one does that becomes really quite crucial, it seems to
21 me.
22 MR. GOSSELIN: Again, sorry about the confusion.
23 I think we can go back, depending on the schedule,
24 if you want to slot --
25 CHAIRMAN FROINES: Well, the Panel cannot
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
43
1 critically evaluate your process unless you provide the
2 process to the Panel.
3 DR. GLANTZ: Well, do you think you could do it
4 this afternoon?
5 I mean, I would kind of like to see it this
6 afternoon, so we can think about it and discuss it more
7 tomorrow if we need to.
8 MR. GOSSELIN: For this afternoon, we can get the
9 latest priority list that we report out and sort of side by
10 side denote which one of these either have requests for
11 monitoring in or monitoring data, and that way it will be
12 comparable to illustrate that most of these on the top of the
13 list are in the risk assessment process and are sort of in
14 the que for monitoring, and it is a matter of managing the
15 timing of getting the documents --
16 CHAIRMAN FROINES: Is that correct, Lynn?
17 MR. BAKER: I do not mean to correct you, Paul, but
18 I would say that most of these are done rather than are in
19 the que for monitoring.
20 CHAIRMAN FROINES: Well, let me ask a very direct
21 question.
22 Of the four compounds that you are proposing to
23 bring before this Panel, the ranking on oncology is zero for
24 three of the four.
25 There is no carcinogenicity evidence in three of
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
44
1 the four compounds that you are bringing forward. I suspect
2 that carcinogenicity is a reasonably important end point.
3 So, somebody has made a decision some place about
4 this. So, we have naled coming through, which is ranked 28,
5 for which there is no carcinogenicity data.
6 Why are we doing that instead of propargite or
7 chlorothalonil, are on the top of the list, for which he just
8 finished saying, there is monitoring data already in
9 existence?
10 Why in terms of your priority system aren't we
11 getting the compounds that you have deemed to be the most
12 important, and why are we getting number 28, which has a
13 relatively low ranking in the terms of the numbers in your
14 own table?
15 MR. GOSSELIN: Two reasons.
16 One is that the science, chronic effects, we do
17 have other concerns, and naled, in particular, would be, I
18 believe it is a cholinesterase inhibition issue.
19 So, one of the issues is that the documents that
20 you see coming forward, our priorities for us for risk
21 assessments because of some adverse health effect that was
22 identified --
23 CHAIRMAN FROINES: That does not answer my
24 question.
25 I think I asked, why is it we are getting naled
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
45
1 instead of the highest priority chemicals which have four's
2 all the way across the top, except for the NOAEL.
3 MR. GOSSELIN: Because, again, without going back
4 into how we planned this process out years ago, these are the
5 documents now that are ready to be brought forward.
6 Again, going back, naled being 28 versus some of
7 the other materials, to put the significance on that number,
8 I think, would overstate the relative ranking.
9 CHAIRMAN FROINES: It is your system.
10 MR. GOSSELIN: What I am saying, in a nice way, is
11 that this is probably a historical remnant of a time before
12 we actually had the process lined out that we have now.
13 DR. GLANTZ: Okay.
14 But I think, and I'm willing to accept that, but I
15 think what we want to see is the current process and the
16 justification of the current process, so that you are working
17 and we are working on the important things and that we all
18 agree that they are important things.
19 It may be, and that is why I was suggesting may be
20 you should redo this based on more current usage data, if you
21 have it, and it may be, based on what you just said, that if
22 there are other end points other than carcinogenicity, that
23 need to be considered in the ranking, that needs to be
24 explicitly presented.
25 Because the whole idea of prioritization is to
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
46
1 ensure that people are spending their time on the important
2 things.
3 I mean, it may be that what you end up doing is
4 fine, but the material you have given us does not seem to be
5 supporting that. But what I hope that you will be able to do
6 this afternoon is put forward a stronger case for why you are
7 doing what you are doing, or alternatively, to put it forward
8 in a way that we can suggest how you might want to change it.
9 I mean, if you cannot do it this afternoon, we can
10 do it tomorrow, but I would rather see it this afternoon.
11 MR. GOSSELIN: I think, what we are facing right
12 now and sort of the schedule that we have now, is, again,
13 largely reflective of what our priorities are for risk
14 assessment, because these are priorities because we have
15 identified adverse effects, and secondly, based upon
16 efficiency of actually getting documents through.
17 DR. GLANTZ: Right.
18 But I think we should go on to the next thing
19 because we are kind of repeating ourselves. We understand
20 the general principles that you are advocating, but we want
21 to see the specifics to make sure we agree with the way you
22 are doing it.
23 CHAIRMAN FROINES: But the Panel wants to know why
24 and how you came to that conclusion.
25 That was the point of this.
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
47
1 The point of this was to ask the question, how did
2 you come to this conclusion? Why did you come to this
3 conclusion, and what are your conclusions?
4 That is what we wanted you to tell us.
5 It does not help us to tell us this is the way
6 things are because this is the way things are, which is what
7 I interpreted that last sentence to be. It is sort of like,
8 we're here, because we're here.
9 So, I do not have the slightest idea, to be
10 perfectly frank, how you came up with those four compounds
11 that you are going to bring forward to this Panel. How
12 within the overall scheme of things, how did you end up
13 deciding on those four relative to the other 23 compounds?
14 MR. GOSSELIN: The short answer is that the work
15 was done on those, and they were able to be brought forward.
16 DR. GLANTZ: May I just interrupt?
17 I think that we have made very clear the questions
18 we have. Rather than answering them right now, we should --
19 you know what the questions are, and you know what we want to
20 hear, and I think we should terminate this part of the
21 discussion until this afternoon when you can come back with a
22 more precise set of answers.
23 I do not think it is fair to them to keep beating
24 on this without giving them a chance to contact their offices
25 and get the specifics that we are asking for.
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
48
1 I think they understand the problem. So, I would
2 suggest that we go on to the next Agenda Item and come back
3 to this.
4 What time do you think you could -- could you do it
5 this afternoon, do you think? Or maybe later in the
6 afternoon, would that give you enough time to prepare?
7 MR. GOSSELIN: Why don't we call and see what the
8 status is there.
9 DR. GLANTZ: I mean, I really think, given the
10 importance of this, I would really like to get to it this
11 afternoon, so, if we want to think about it overnight, we can
12 discuss it some more tomorrow.
13 But also, I think we want to make sure they have
14 enough time to come forward with the best presentation they
15 can. So, with those two balancing things, maybe late in the
16 afternoon would be the time to bring this back.
17 CHAIRMAN FROINES: I agree.
18 I think that, Paul, the important thing is that,
19 say these are the compounds that we had things to go forward
20 with, we are talking about the general process of setting
21 priorities.
22 So, sort of saying, well, we had some documents in
23 the pipeline, does not really answer the question, do you
24 understand, precisely, because, quite frankly, this is a
25 1996 document.
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
49
1 It was written, therefore, probably in 1995.
2 Therefore, there have been four years to focus on
3 your high priority chemicals. It is not as though there
4 hasn't been sufficient time to focus on those things which in
5 1995 you thought were the most important.
6 So, to say that we have not had time to get to the
7 other one's doesn't fly.
8 So, think about it.
9 DR. GLANTZ: I think we should go on.
10 CHAIRMAN FROINES: No, but I want to make it clear
11 on what some of the issues are.
12 DR. GLANTZ: I think you have.
13 CHAIRMAN FROINES: I appreciate both you and Paul
14 trying to help the process.
15 I think it needs help.
16 DR. GLANTZ: I think we should move on.
17 I think the issues are clear. I really do. I
18 think you have made them clear. Everyone has made them
19 clear.
20 They understand them. Give them a chance to come
21 back with the answers now, John, then we can, like, tear them
22 apart.
23 CHAIRMAN FROINES: I'm not interested in tearing
24 them apart.
25 DR. GLANTZ: I know. I am being flippant.
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
50
1 CHAIRMAN FROINES: We will do the best we can on
2 how we are going to deal with the prioritizations and the
3 pesticides that we have.
4 DR. GLANTZ: The other thing, I think, which is
5 just to add to what John said, I mean, however you got to
6 where you are today, I think it is real important to talk
7 about how you are going to be doing it in the future, too.
8 So, to the extent that there is anything right or
9 wrong with where we are at right now, we want to make sure
10 that the next group of things coming into the process are the
11 things that should get the highest priority.
12 MR. GOSSELIN: That is the main outcome to get to.
13 CHAIRMAN FROINES: Would you like a break?
14 Let's take a break, and then we will move to the
15 person who was actually ahead on the Agenda, from EPA, and we
16 will get to that issue.
17 (Thereupon a brief recess was taken.)
18 CHAIRMAN FROINES: I'm very pleased to welcome Mr.
19 Luis Suguiyama, from United States Environmental Protection
20 Agency, who has agreed to come and talk about pesticide
21 priority issues at USEPA.
22 At this point, and you can see from the Agenda,
23 that he is talking about reassessment of adult and child
24 tolerance for pesticidal residues in food, and so, thank you
25 very much for taking time to come out and join us.
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
51
1 We appreciate you being here very much. So, we
2 will leave it up to you.
3 MR. SUGUIYAMA: Good morning. It is a pleasure to
4 be here in San Francisco.
5 I would like to thank the Panel for inviting me to
6 be here. To me this is an honor. California is almost like
7 my second home, and I always welcome the opportunity to be
8 here. I would also like to extend my thanks to Bill and also
9 Pete and Peter and also Eleanor who were also instrumental in
10 extending the invitation to be here, and they did most of the
11 arrangements for me.
12 My thanks to all of you.
13 What I wanted to do is to follow, and I want to
14 give an overview as to where we are in terms of the work that
15 we are doing in assessing all pesticides in EPA.
16 I think that all that information will be useful to
17 you as you are in the process of prioritizing and also are
18 already conducting this risk assessment.
19 One of the things already coming out of this, just
20 as I listen to what transpired this morning, is that one of
21 the commitments we are making is that we are all going to
22 have to work very closely with CDPR, more closely than we
23 have in the past to try to schedule and also share more of
24 these scarce resources that we have in this process of risk
25 assessment.
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
52
1 What I want to do is, if the Board will allow me to
2 move up so that I can present my overheads, and I will
3 probably be standing by the machine.
4 I think we are going to start by giving you an
5 overall look as to what EPA is all about in Washington, D.C.
6 My intent was not for you to say, wow, oh, about
7 EPA or, ah, about EPA, but just to place properly where the
8 work on pesticides is being done at EPA.
9 Of course, we do have the administrative component
10 of the agency, and Mrs. Carol Browner is our current
11 Administrator.
12 Then we have the Programmatic Offices and then we
13 have the Regional Offices.
14 Most of the work that is being done in California
15 is being coordinated jointly with Region number 9, which is
16 housed here in the San Francisco area.
17 The primary regulatory work on pesticides is being
18 done by the Office of Prevention, Pesticides and Toxic
19 Substances. This is the office that we normally refer to,
20 and just using the Federal acronym, OPPTS.
21 So, when you have questions about the risk
22 assessment that is being done on certain pesticides, this is
23 the office that you will be looking at for the most part.
24 But that is not the only office that is working on
25 with EPA pesticides. We do have the Office of Air and
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
53
1 Radiation. They are working, for example, right now with
2 methyl bromide. So, we work very closely with them on issues
3 that involve methyl bromide.
4 We have the Office of Enforcement and Compliance.
5 We work with the states in terms of assuring that practices
6 are being done correctly.
7 We have the Office of the General Counsel. They
8 look at the issues, the legal issues concerning pesticides,
9 and there is a significant amount of work that is being done
10 in the regions in terms of pesticide monitoring and
11 inspection.
12 One area, or one office that you also need to
13 probably to be careful, because, the work or the issues that
14 are being addressed by the Board are in the threshold of new
15 policies or new research, would be the Office of Research and
16 Development.
17 If we dissect the work that is being done in the
18 Office of Pesticides, Prevention, Pesticides and Toxic
19 Substances, right now we are divided.
20 Basically, it has changed. Now we are three
21 offices, with OPPTS. We have Office of Pesticide Programs.
22 We have the Office of Pollution Prevention and Toxics, and we
23 have a new Office of Science Policy, because with the advent
24 of new science, there are a number of issues that need to be
25 addressed separately.
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
54
1 In the Office of Pesticide Programs, you see
2 several divisions which do the work. I am housed in the
3 Registration Division.
4 My job is, I'm the Branch Chief of the Fungicide
5 Branch. I do most of their regulatory management concerning
6 fungicides, such as fungicides already mentioned this
7 morning, chlorothalonil, those are in my Branch.
8 But we also do the work on insecticides and
9 herbicides and nematocides.
10 When you were talking about older chemicals, this
11 is the Office that you are going to be looking at, the
12 Special Review and Registration.
13 So, right now all of the risk assessment that is
14 being done with organophosphates are being done in this
15 Division. Again, this is a risk management component. Okay.
16 Just to make sure that we are clear, there are
17 three risk management divisions in the Office of Pesticide
18 Program.
19 We have the Registration Division. We have the
20 Special Review and Reregistration. We have the
21 Antimicrobials Division. They are looking at household
22 pesticides.
23 We have also the Biopesticides and Pollution
24 Prevention Division. They are looking at the biochemicals.
25 Those are the four major risk management for our Divisions.
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
55
1 We have two basic Science Divisions. We have the
2 Health Effects Division. They are looking at all the human
3 health effects of chemicals.
4 We have the Environmental Fate and Effects. They
5 are looking at environmental fate and ecological effects.
6 This is the basic office that is doing pesticide
7 assessment registration work in EPA.
8 Let me put up these transparencies, because this
9 Office of Research and Development is something that we may
10 want to take a second to look at.
11 There are many components of this office that are
12 doing technical research, the basic research, and one of the
13 things that I wanted to get through future contacts with this
14 Board is to see whether there might be some issues that are
15 coming out that need to be consulted with our Office of
16 Research and Development.
17 For example, there are issues that may be important
18 to you, environmental carcinogenicity, where we may have
19 human exposure and atmosphere science divisions, issues that
20 you guys are really in the threshold of trying to assess here
21 in California.
22 Okay.
23 I wanted to touch briefly, besides the EPA, as to
24 what are the pesticide laws that we are currently working
25 under. We have the main two are FIFRA, which is the Federal
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
56
1 Insecticide, Fungicide Regulation Act. FIFRA is the
2 pesticide law, the basic pesticide law in the United States.
3 Under FIFRA we have many sections. Under Section 3
4 would be registration requirements. Section 4, are
5 reregistration. Section 6, are detailed reports. Section 18
6 are State Emergency Issues. Section 24-C is Special State
7 Registration Local Needs.
8 The second major component, and this is where the
9 tolerance assessment process would come into play, the
10 Federal Food, Drug and Cosmetic Act of the United States.
11 This is where we, this is the authority that gives us the
12 power to establish policy and regulate policy accordingly.
13 In addition, there are other Federal laws that are
14 critical to the work that we do on pesticides.
15 This is a Safe Drinking Water Act. We have the
16 Endangered Species Act. We have the Clean Water Act. We
17 have the Clean Air Act.
18 We have TSCA, which is the Toxic Substances Control
19 Act. We have the Occupational Safety and Health Act.
20 We have state laws. You have that in California,
21 and we have some municipal laws.
22 For example, I believe that San Francisco has
23 municipal laws that affect the use of pesticides. Then we
24 have other, just the administrative component, the Freedom of
25 Information Act, Federal Advisory Committee Act, the Federal
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
57
1 Administrative Procedures Act.
2 These are very important, because these require us
3 to disclose information and share the information with the
4 public.
5 As you all know very well, in 1996, FIFRA, which is
6 the Federal pesticide law and the Federal Food and Drug, they
7 were amended in a major way by the Food Quality Protection
8 Act, which is known as FQPA.
9 This is the Act that really has changed the way
10 that we are assessing and reviewing pesticides. I came to
11 the program in 1997.
12 I was working in International issues, and I became
13 a branch chief in 1997, right after the Act was passed. I
14 can assure you though that in 1997, my hair was very dark.
15 I notice it is becoming grey. I do not know if
16 that is from FQPA, but it is challenging.
17 We have changed major components. We have now a
18 single health-based safety standard for residues in food.
19 Now, every time we issue a registration or we allow a new use
20 for a chemical, we have to make -- we have to assure the
21 public that we can make a reasonable certainty that there
22 will be no harm for allowing that use in the foods.
23 We have special permission for the protection of
24 infants and children. I mean, this is the major component of
25 the FQPA, following the advice from the National Academy of
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
58
1 Scientists Report.
2 We have limitations on how benefits are being
3 considered in the risk assessment. FIFRA was for the most
4 part a risk benefit, a base statute, actually with FQPA how
5 benefits can be considered.
6 For example, if we have a chemical that potentially
7 can harm children, or children are more susceptible or
8 sensitive to that particular chemical, if benefits were high,
9 they would not apply. We cannot support the use of that
10 chemical just because benefits are very high.
11 There would be also a requirement for tolerance
12 reassessment, that we are going into later, the uniformity of
13 tolerances, and this is uniformity between Federal and also
14 the state level of tolerances.
15 Endocrine disrupter or the potential for the
16 chemical to disrupt the endocrine system, that is a science
17 policy that you should, we are still trying to work on.
18 We have consumer's rights enforcement, consumers
19 right to know, and this is under just the general concept of
20 residues in food.
21 Under the registration component, it actually
22 renewed the pesticide reregistration program, also provides
23 provisions for assisting the registration of chemicals every
24 15 years, and this is for new chemicals.
25 It promotes faster registration of safer chemicals,
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
59
1 to reduce risk and also allows for specific provisions for
2 minor use pesticides and the use of antimicrobials.
3 In a nutshell, these are actually the major changes
4 that FQPA placed on the assessment of pesticides.
5 What are some of the impacts that we are seeing?
6 FQPA is actually creating the following impact.
7 There will be cancellations for the older chemicals. We have
8 already seen that.
9 You have already seen what happened with methyl
10 parathion, and we are going to see more in the future.
11 Some petitions for new registrations are going to
12 be denied, because pesticides cannot meet the safety
13 standards.
14 Remember that right now we are not just looking at
15 the risk where a new use study is being allowed but also we
16 are looking at cumulative risk and also pesticide would have
17 a common similar action. Where some of the OPs,
18 organophosphates, what we would like to know is, how we are
19 going to be able to regulate them because they share one
20 common mechanism, which is the cholinesterase inhibition,
21 which is the ChE inhibition.
22 Consumer information is going to be more critical.
23 People will have now the right to know what pesticides are
24 going to be used nearby, and that is something we are trying
25 to work with the public, also.
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
60
1 This is a schematic all of the steps that now a
2 chemical will have to undergo as we are looking at the
3 registration or reregistration process.
4 The Panel Members will get a copy of this table.
5 This is a very complex and very detailed summary of all of
6 the steps that the chemical has to undergo, one is being
7 reassessed or whether there is a new registration.
8 There are two components. Basically, we would like
9 to determine what is the human health hazard. We would like
10 to know what are the human health effects. We would like to
11 know where are the ecological and environmental fate.
12 Going back to my chart. This is being done by our
13 HED, which is the Health Effects Division, of the OPP. This
14 is being done by our Environmental Fate and Ecological
15 Effects Branch.
16 In the human health component, we would like to be
17 able to establish eight points of concerns, determining what
18 is the work exposure, determining residential exposure and
19 determining what is the dietary exposure.
20 These are all based on data, summaries and
21 extensive data that has already been presented to the agency.
22 From our ecological standpoint, we would like to
23 determine what is the drinking water exposure, determine the
24 ecological exposure and establish end points for consistency
25 studies.
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
61
1 This is the area that we refer to that establishes
2 the NOAELs, no adverse, no adverse effect levels that we are
3 going to be using. Then, after that step, we will try to
4 establish what is the reference dose, what is the level that
5 we are going to regulate upon the chemical.
6 We also would like to know what is, whether the
7 chemical is a carcinogen or a non carcinogen, determining
8 what is the element of human exposure and whether the
9 chemical might be related to other compounds.
10 We are trying to characterize human health risk,
11 characterize ecological health risk. I just went through
12 this process in about a minute or so, but you know this is a
13 very complex, very complicated process.
14 To get a new active ingredient, if we had a
15 complete data set to get to these stages, I would say it
16 would take us a full year.
17 We are looking at continuous reviews of committee
18 meetings to establish and to properly characterize what is
19 the hazard for this chemical on humans as well as the
20 environment.
21 Once we do that, one of the things that we would
22 like to do is to begin to share what is the risk assessment
23 and then properly modify that and then make a few regulatory
24 determination whether the chemical should be registered or
25 whether those uses should be reregistered for that matter.
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
62
1 This is a very complicated process. Again, there
2 is extensive more detail available as to what are all the
3 steps that the agency follows during the risk assessment
4 process. But I just wanted to provide an overview of the
5 major steps that are taken.
6 One good example of that is actually on a copy of a
7 document that the Panel Members will have, is the latest risk
8 assessment for one of the organophosphates, which is phorate.
9 That document actually details, for each one of
10 these issues, what has the agency determined, and this is
11 after we have talked to the registrant, and then the risk
12 assessment has been revised.
13 In terms of exposure, I brought this chart,
14 transparency, thinking it would be very worth while for the
15 work that has been done here.
16 We would like to see all of the major routes of
17 exposure to chemicals, and this is starting from the house,
18 the use in the field, proper disposing of the chemical,
19 potential leaching into the groundwater and back into the
20 house.
21 CHAIRMAN FROINES: Can I ask you a question?
22 On the phorate document, that is dated September 2,
23 1999, how many documents like this do you currently have?
24 MR. SUGUIYAMA: I will touch that in a minute.
25 One of the key things, when I was asked to come to
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
63
1 EPA, is to provide a basis as to how we prioritize chemicals.
2 I am sorry that I am just jumping through the risk
3 assessment process. I will be here the rest of the day, if
4 you have more or specific questions about the process itself.
5 Prior to FQPA, most of the more toxic chemicals
6 will be in review under our process that we call special
7 review. So, I'm talking about, here about pre 1996, when we
8 saw that we had a problem with certain chemicals, chemicals
9 will be put under special review for specific risk
10 considerations.
11 For example, you will find a significant amount
12 chlorethoxyfos, which is the very worst category for priority
13 review, we will put the chemical under special review.
14 This process now, is being overtaken by the work
15 that we are doing under FQPA. FQPA was very specific in
16 terms of the prioritization scheme that we need to follow.
17 Still based on the risk and hazard, how risky or how
18 hazardous is chemical exposure going to be, there were three
19 groups that were created.
20 Group number one were the organophosphates,
21 carbamates, organochlorines, the human percentages we are
22 talking about the B1 and B2, the high hazard inert
23 ingredients, and pesticides whose RfD has been exceeded, that
24 means the risk is over 100 percent of the rest of those.
25 DR. GLANTZ: How did you come up with that group
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
64
1 one?
2 I mean, was there a process there or some
3 scientific justification, or does that just seem like
4 reasonable things to stick together?
5 MR. SUGUIYAMA: I think, my knowledge is not all, I
6 am just providing an overall, one, we were looking at
7 grouping in terms of risk and hazard.
8 We were looking at probably the acute component,
9 that is why probably why organophosphates was at the top of
10 the list.
11 We were looking at the acute, going from acute to
12 chronic, and looking at hazard and human health plays a major
13 role.
14 Informally, there was another grouping that was
15 done. I will try to provide that later, but for example,
16 even the first group is broken down in organophosphates, then
17 the cholinesterase inhibitors becomes the number two group,
18 then the carbamates, because the carbamates can be broken
19 down to two separate groups, because of the different modem
20 of action.
21 The organophosphates will be the next one, because
22 we only have a few remaining chlorines now being registered
23 here in the United States.
24 DR. WITSCHI: How is the group two different from
25 one?
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
65
1 MR. SUGUIYAMA: The group number one is the B1 and
2 B2 percentages. These are the other possible human
3 percentages which would be deceased under EPA clarification
4 for percentages.
5 We are looking at the C, possible, you know human
6 percentages.
7 DR. BLANC: How does a high hazard, non inert, as a
8 pesticide make it into group one if it is not a carcinogen or
9 into group two?
10 To tell you the truth, let's take manep, for
11 example, I actually do not know the carcinogenic status, but
12 let's assume it is, for point of discussion, that weren't a
13 carcinogen.
14 MR. SUGUIYAMA: It is B2.
15 DR. BLANC: Let's suppose it weren't.
16 I am just -- hypothetically, let's take a
17 hypothetical chronic neurologic toxin which is not a
18 organophosphate and not an organoflorate by this
19 classification, how would it be anything but group 3?
20 Is there an equivalent or parallel to the high
21 hazard inert ingredient to high hazard active ingredient
22 which is not on the basis of toxicity, not on the basis of
23 carcinogenicity if it is not an organophosphate or carbamate?
24 MR. SUGUIYAMA: When we have cases such as that, we
25 would look at the exposure component to see if the exposure
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
66
1 is very high.
2 If we believe that it is -- then we would make it
3 into group number one.
4 CHAIRMAN FROINES: The classic example would be
5 phenylethyl propionate. Phenylethyl propionate is none of
6 those, but it is a neuro toxin.
7 DR. BLANC: How did it make it into group 1,
8 because of its RfD?
9 MR. SUGUIYAMA: It will not be in group 1 right
10 now.
11 There is another component for methyl bromide, and
12 because of the agency, methyl bromide is one of my compounds
13 in my branch, and because of the phasing out, which was
14 scheduled in the year 2000, we actually did not include
15 methyl bromide to group number 1, thinking that uses would be
16 gone in less than a year.
17 Now, those uses are being extended to the year 2003
18 and 2004, at different levels of phasing out. Therefore, now
19 we are trying to see when the agency will be looking, and
20 also the quantity uses have been accepted in some cases for
21 methyl bromide, but it was not one of our priority chemicals
22 to be reassessed.
23 DR. BLANC: So, there are some potential pitfalls
24 then in your prioritization scheme, you would say?
25 CHAIRMAN FROINES: Does the actual law list, create
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
67
1 a list like this?
2 MR. SUGUIYAMA: Yes.
3 The law actually requires us to prioritize the
4 chemicals. What the agency did is publish a Federal Register
5 Notice indicating a ranking of the chemicals, and that is
6 also included in the package.
7 Okay. There were several groups in some chemicals
8 that were given, and these are relative rankings as to how
9 the agency will proceed in terms of the reassessment process.
10 Let me jump a little bit, and let me tell you
11 that -- let me clarify something. This is a priority session
12 scheme under the tolerance reassessment and reregistration.
13 There is another priority session process that the
14 agency follows, and this is under the registration for
15 chemicals, and here we are looking at different components.
16 We are looking at methyl bromide on alternatives.
17 This is not about reassessing methyl bromide. It is about
18 assessing the alternatives to the use of methyl bromide, the
19 alternatives to the use of organophosphates, the critical use
20 chemicals, the critical pest control for agriculture, minor
21 uses and then the priorities by the registrants.
22 This is the second priority scheme that is being
23 used for now in EPA. What are the pitfalls? Why is it
24 always possible to put a priority to say that we should work
25 with chemical number one, chemical number two?
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
68
1 That also touches another question that was
2 proposed to DPR.
3 Okay. Remember, again, when EPA is assessing a
4 chemical, we cannot just say we will start the reassessment
5 tomorrow and end in six months, because that is probably how
6 much it takes for the reassessment process to be completed.
7 It doesn't work that way, for the following
8 reasons. Each chemical or each group of chemicals has its
9 own set of difficulties.
10 Data for the most part could be complete, could be
11 incomplete and data is coming into the agency at different
12 places. So, it is not always possible for the agency to say
13 we will start work and by tomorrow we will finish in January
14 2000.
15 Okay.
16 So, there is a whole process of priority,
17 prioritizing on the chemicals and also scheduling completion
18 of the chemicals, and that, perhaps in a way, explains why it
19 is not possible to follow the 1, 2, 3, 4, 5, once the
20 priority scheme has been developed.
21 It is a function of data. It is a function on the
22 complexity of the chemicals, and remember for some of the
23 older chemicals, there might be 1, 2, 3, in some cases 12
24 registrants working together in preparation of the data, the
25 prep work.
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
69
1 To do that takes years. It is not something that
2 can be done over time. Something for the Board to consider
3 while working with Cal EPA is also to look at the timing and
4 the proper packaging of the reviews, whether they can be done
5 in a certain time, before just saying that everything has to
6 be according to a certain schedule.
7 Something that I wanted to share with you, this is
8 publicly available now, is the schedule of objectives for the
9 OPs, for the organophosphates.
10 OPs right now is the main priority for EPA. That
11 is what we are working on.
12 There are many organo -- or there are about six of
13 them. There are 43 organophosphates, I believe. There are
14 six of them that are not listed here, because the registrants
15 have actually requested voluntary cancellation, but for the
16 one's -- this in addition to methyl parathion and the other
17 one's we have already completed.
18 This is the planned schedule of the actions until
19 the year 2001. So, by September, a year from now, the agency
20 expects to complete all of the risk assessment and the risk
21 management or the risk mitigation with the OPs to be
22 completed in about a year.
23 Okay. This is our schedule. This is something
24 that I think we need to work closely with DPR to see how the
25 work on these chemicals matches the work that is being done,
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
70
1 and we are already sharing a lot of information here.
2 Okay.
3 There is one issue that remains with OPs that may
4 play a role later. At the beginning of the year 2000, the
5 agency also expects to issue a decision as to how we are
6 going to assist in the OPs group now with a common mechanism
7 of function.
8 Depending on how we will determine it, it could
9 have an impact, and possibly all the uses of the OPs could be
10 reassessed.
11 We do not know whether that is going to happen or
12 not. Possibly there could be additional changes to the OPs
13 as a group. Okay.
14 In addition to the organophosphates, there are
15 other chemicals that are being reviewed. For the current
16 fiscal year, we expect completion of the following chemicals:
17 Bendiocarb; captan -- captan would be very critical for
18 California; EPTC; folpet; formetanate HCI; lamprecide;
19 niclosamide; pebulate; sulfotep; TPTH.
20 TPTH is also used extensively here in California.
21 These are the voluntary cancellations for some of
22 the others that we have already received here at the agency.
23 That means that the uses would be canceled.
24 Work on this one would be done. So, you should
25 look at for the following fiscal year, which starts next
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
71
1 month, the agency has already made plans to complete REDs or
2 the work or the reassessment according to this time table.
3 Triallate, which is expected to be completed in
4 December of 1999. The beginning of the year 2000, benomyl,
5 terrazole, thiabendazole, thiophanate methyl, imazalil,
6 carbofuran, endosulfan, oxamyl, propargite and vinclozolin,
7 it should be close by March of the year 2000.
8 This is the schedule of all of the chemicals for
9 which a RED would be completed.
10 There is a copy of all of the REDs in your package
11 that the agency has completed. I am not going to show it up
12 here in transparencies because it is too extensive, but one
13 of the things that we have to consider is that REDs that were
14 completed prior to 1997 bear watching, because they do not
15 include some of the FQPA requirements.
16 So, those that were completed after 1997, such as
17 chlorothalonil, which was completed just very recently, those
18 are FQPA, I will say EPA compliant, following the FY 2000
19 issue, FQPA compliant REDs, which, that means we have
20 incorporated many of the new requirements that are being
21 asked for by FQPA.
22 Let me finish my presentation here with an
23 indication, most of the information is already available and
24 EPA is pulling out more and more information for public
25 consumption, and this is in our Website.
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
72
1 You have to link to the specific Website of
2 pesticides, which will give you a site map. This Website
3 also contains the specific sections, come up to you very
4 quickly about FQPA, about OPs, things that you can go, you
5 will find all of the information, the most current
6 information on OPs Website as well as general information
7 about pesticides.
8 So, this is the information that I have. I know
9 that this is just a rush through overview. There is a lot of
10 work that is being done in the agency.
11 The challenges are very hard. Reassessing all
12 these pesticides is not an easy process. I am glad that you
13 guys are also doing that in California.
14 We're trying to do the best we can at EPA with the
15 older chemicals.
16 Please remember that you can prioritize chemicals
17 according to their hazard and their risk. You also have to
18 make sure that their schedule can fit within a time table.
19 That doesn't always work that way, because data are
20 not always complete. One of the things that you need to do
21 is to do a fair and objective risk assessment.
22 You have to have at least a complete database, and
23 that is something that registrants and regulatory agencies
24 are always going to work to try and develop.
25 Okay. That is all. If you have any questions or
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
73
1 comments.
2 DR. FRIEDMAN: I am just curious about possible
3 overlap between your agency and the FDA, in terms of
4 evaluating foods.
5 How do you define food safety from your point of
6 view versus what the FDA would be concerned about? Is it
7 just a matter of what chemicals get onto the food versus, for
8 example, there is some concern about beef being fed estrogen,
9 cows being fed estrogen.
10 Who would be responsible for that? Would that be
11 EPA or FDA?
12 MR. SUGUIYAMA: FDA.
13 DR. FRIEDMAN: So, what is the definition or the
14 difference?
15 MR. SUGUIYAMA: If these are pesticides under the
16 definition of a pesticide use, then it comes under the
17 authority of EPA.
18 If they are food additives and also supplements to
19 foods that would appear in foods, for example, things fed to
20 cattle, then that is FDA.
21 DR. FRIEDMAN: Thank you.
22 MR. SUGUIYAMA: Now, we are seeing more and more
23 chemicals that are actually, could be used both ways, older
24 food additives or supplements to food that are, that we
25 received requests, for example, as a plant growth regulator.
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
74
1 In that case, we would do the risk assessment and
2 take a look at the FDA review, but we are going to start the
3 process from the very beginning, because most of those
4 reviews could be very old.
5 CHAIRMAN FROINES: Are the background documents
6 that provide the basis for the decisions in here available on
7 the Web?
8 MR. SUGUIYAMA: You said background documents.
9 Are you talking about the basic reviews?
10 CHAIRMAN FROINES: Yeah.
11 In other words, if one wanted to learn what were
12 the criteria that gave you the RfD, QRfD, for example.
13 MR. SUGUIYAMA: Those are not available, but in
14 most part, we would put out these summaries of the risk
15 assessments.
16 Now, through the Freedom of Information process,
17 you can ask, if you, citizens can ask for information, and we
18 can provide, but it has to be screened, because we do have
19 some regulations concerning the release of business
20 information, we cannot always just release anything.
21 Everything has to be screened, so that process
22 would take time.
23 For the Board, my recommendation would be use CDPR,
24 because we can exchange, because they are a sister, we can
25 exchange, we can provide information to them.
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
75
1 CHAIRMAN FROINES: Well, Mike, that was precisely
2 my question, which is, since we are interested in perhaps
3 improving the pace at which pesticides are listed as toxic
4 air contaminants, theoretically, we could take this document
5 and use it as the basis for determining the compound a toxic
6 air contaminant, but we would want DPR to be developing a
7 background document on the underlying literature.
8 If you had 5, 10, 20 of these things, this process
9 could move rapidly if we could use this kind of information.
10 MR. SUGUIYAMA: The REDs become a public document,
11 and the CDPR has a copy of the RED.
12 The question, as to why CDPR actually assesses,
13 which I think was noted as 39, I'm not attempting to go by
14 the response of CDPR, but EPA has completed it, so, there is
15 no need for them, they do not need to wait until the 28 or
16 29, they can go ahead, do it.
17 CHAIRMAN FROINES: It is number 2, so, it is an
18 interesting compound.
19 If you have done it, we should have it.
20 MR. SUGUIYAMA: I'm sure that the information has
21 been given to you and shared with CDPR.
22 MR. GOSSELIN: One other compelling need for us to
23 do on our assessment, and we have been working real closely,
24 exchanging information on these assessments, and we have been
25 looking to actually use completed REDs, is sort of the
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
76
1 foundation on the hazard identification portion for ours to
2 kind of speed up the pace of completing the work on
3 assessment.
4 But one of the principal focuses we look at is not
5 in contrast to EPA, not from a national perspective, but from
6 the unique exposure scenario facing California, involving,
7 principally involving workers or toxic air that are not going
8 to be part of the RED, but the toxic evaluation essentially
9 should incorporate all the same information.
10 MR. SUGUIYAMA: Allow me to share something.
11 In or on about October, we are going to go public,
12 however, we are going to be showing the work plan for the
13 work that will be done by the Registration Division in terms
14 of new uses, and this is the second prioritization scheme
15 used by EPA.
16 There was a question that was raised about MITC,
17 and right now we have received applications of two methyl
18 bromide alternatives.
19 These are not new compounds in itself. They
20 actually break down into MITC, something that Paul will get
21 into.
22 We are expecting to complete the risk assessment
23 for MITC related compounds in the second quarter of the year
24 2000. So, one of the key things that we need to do is work
25 closely with CDPR, because although we may differ in how
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
77
1 often we regulate these chemicals, but I think, the hazards,
2 we need to be consistent on how we our asses hazard to MITC.
3 The compound that I am talking about is
4 dimethoxane. Dimethoxane actually breaks down quickly into
5 MITC.
6 So, we are actually regulating all of these
7 chemicals under just the common, which is the methyl oxide.
8 There might be other compounds.
9 This is going to be, all of this is going to be
10 published in the current register, so you will have an idea
11 of what the uses would be that are coming.
12 It would be undergoing a full EPA review, also.
13 This is aside from the RED process.
14 DR. ATKINSON: Does your Website list the
15 environmental fate data which is required for registration or
16 reregistration?
17 MR. SUGUIYAMA: Are you talking about per chemical
18 or basic requirements?
19 DR. ATKINSON: The basic requirements.
20 MR. SUGUIYAMA: The basic requirements would be
21 under the Code of Federal Regulations.
22 If you go into our Website and you take a look at
23 the laws and regulations, there will be a site that says Code
24 of Federal Regulations and the basic requirements.
25 I know that this Board actually works on air
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
78
1 monitoring. We understand that industry is a regulated
2 industry that has been working for the last ten years and has
3 spent quite a bit of funds developing a new model to try to
4 determine what is the risk of chemicals arising from the
5 spray drift.
6 We have been privy that the model has been
7 developed, and we are going to start looking -- has been
8 reviewed by our science and advice panel, and we understand
9 that we are going to be looking at a test model to see
10 whether we may be able to determine what is the potential
11 risk of chemicals resulting from spray drift, and that is
12 something that we are going to share with the work being done
13 on this Board.
14 It could be critical to the work. Monitoring for
15 pesticide sceneries can be very difficult, because there
16 isn't a model, a continuous model that can actually monitor
17 or mimic what's happened with a chemical in the environment.
18 Also, once we humans become exposed, so, this is
19 the first attempt to try to predict what would happen to the
20 chemical, what is the fate of the chemical, which is, if it
21 is being sprayed by helicopters, by aircraft or by ground
22 applicators, so it will be interesting to see what the
23 utility is, and that is something that I will share with the
24 Board and also CDPR will also know about it.
25 CHAIRMAN FROINES: Thank you very much. We
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
79
1 appreciate it.
2 DR. GLANTZ: Could I just ask one point of
3 clarification?
4 In terms of the risk assessment that you have done,
5 are you saying that all of that information is freely
6 available to DPR to use in its work?
7 MR. SUGUIYAMA: The risk assessment, yes.
8 DR. GLANTZ: Then, what was the material that you
9 had to put in the Freedom of Information Act request for?
10 MR. SUGUIYAMA: Let me clarify it.
11 There are REDs, public document REDs that have been
12 made available. If you go to the Web, you can link, you can
13 actually point on that and you will get a full copy of the
14 RED.
15 Some of the RED documents are over 400 or 500
16 pages, a large document.
17 For the OPs, what we have done is also created
18 summaries. You have a copy of phorate as an example of the
19 many that we have done.
20 If you are, also, if you log into the OP section,
21 you will be able to get the latest risk assessment for all of
22 the OPs.
23 DR. GLANTZ: Right.
24 But you had said earlier that for some material you
25 had to put in a Freedom of Information Act request for some
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
80
1 information.
2 MR. SUGUIYAMA: If you are a public system, we
3 require you to make a request for your request.
4 DR. GLANTZ: Right.
5 But how is that different from what you have put up
6 on the Web?
7 CHAIRMAN FROINES: It is the background documents
8 that are the basis for what is on the Web.
9 DR. GLANTZ: I see.
10 Now -- but those background documents are freely
11 available to DPR?
12 MR. SUGUIYAMA: Some of them are and some are not.
13 We would share with probably DPR, and I would have
14 to go back and check to see what is the extent of the
15 documents.
16 I think decision documents, like they are called
17 DERs, there is summary of the studies that we might be able
18 to share, and we might be able to share the final risk
19 assessment by each of the science divisions, the document
20 that actually spells out, but that information is also, like
21 you were saying, summary of the information that goes into
22 the summaries.
23 But the OP will all depend on how deep you want to
24 go to understand these studies. The other thing is that
25 through regulation, the State also has the regulatory
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
81
1 authority to ask for these types of studies from the
2 registrants.
3 DR. GLANTZ: Yes.
4 But I was thinking in terms of avoiding a lot of
5 duplication of effort. I mean, if you have already procured
6 this information, it is silly to make DPR go procure it all
7 again.
8 It would be a lot easier to get it from you, and
9 then, one of the things that we have done quite vigorously is
10 we have defended our right to make our own decisions here and
11 not necessarily agree with USEPA.
12 I would want DPR to come up with their own
13 assessment and also this Panel with its own assessment, but
14 if you have done a huge amount of leg work in collecting all
15 of this information, which is a lot of work and very time
16 consuming and expensive, it just seems DPR ought to have the
17 benefit of as much as that as they can have so that they do
18 not have to go out and reinvent the wheel after you guys have
19 done it.
20 They might have come to different conclusions, but
21 just collecting all the basic information that you are
22 describing is just a huge effort.
23 CHAIRMAN FROINES: But I would go further.
24 I would say that this phorate document could be
25 used to bring it before this Panel as a toxic air contaminant
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
82
1 document, and Paul was saying a few minutes ago that there
2 may be some special circumstances in California, and that is
3 fine, but there is a point at which the special circumstances
4 is a risk management issue.
5 It is not a risk assessment issue.
6 So, some of the special circumstances, that is not
7 our privy anyway, so, if we wanted to speed things up, one
8 could conceivably bring 20 documents before this Committee
9 that were done by EPA.
10 We have, in what we are going to do this afternoon,
11 are doing a whole list of EPA RFCs that OEHHA has reviewed
12 but has not changed at all.
13 So, there is a precedent, in fact, for bringing
14 documents from the Federal Government that at least bring it,
15 the point of which we always want to fine tune everything to
16 be perfect, but that makes everything take a very long time.
17 If we could speed the process up and fine tune it
18 later, we might actually accomplish more.
19 DR. GLANTZ: I think that is an interesting point,
20 and I guess Paul and the others are out handling the fax and
21 things, but that may be a good idea.
22 It might be that you ought to be reviewing what
23 they have done in the context of your priority list, and it
24 may be, although I have to tell you that these are a lot of
25 work to read, but you could come to us with something like
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
83
1 this that did some large number of compounds all in one fell
2 swoop, and really speed things up if indeed you are satisfied
3 with the work that USEPA has done.
4 I mean, there are instances in the document that we
5 are going to discuss this afternoon where OEHHA did not agree
6 with EPA and suggest modifications to what EPA is doing,
7 which I think is completely reasonable, too.
8 So, I think that, because it looks, just from
9 looking at this, like a huge amount of the homework that you
10 would need to deal with these compounds that has been already
11 done by USEPA, so, I think, that is something we ought to
12 consider.
13 MR. SUGUIYAMA: A couple of issues that need to be
14 addressed.
15 In terms of the basic reviews in EPA, we actually
16 conduct many tiers, reviews of separate tiers.
17 For example, the first tier is done by a
18 contractor, somebody who goes through each one of the studies
19 and goes through the periods and commas to make sure the
20 studies were done at a good level of practice, then they
21 issue a summary, and that second tier review by our
22 toxicologist, by our chemist.
23 That is different than CDPR, also taking a look at
24 those, and that is what we need to talk about, because I am
25 not familiar at the science level as to how much information
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
84
1 is being exchanged, something that we can work on.
2 Now, the issue where we may have differences might
3 be in the interpretation. For example, what is regulatory?
4 We have done joint work with Canada, and some we
5 have agreed and some we have not. We actually have to have
6 Committee Members to agree, and that wouldn't be different
7 with California either.
8 We may have some differences as to what the proper
9 regulatory end point would be, but that can be taken by way
10 of the concentration process of regulating, and we are
11 required to be consistent.
12 Then the point made about the risk mitigation is a
13 different story, because we have to take a look at the
14 national picture, and you guys in the State will have to take
15 a local, your local needs and your risk or exposures would be
16 different.
17 DR. GLANTZ: Right.
18 But the risk management part is not the purview of
19 this review here.
20 DR. FRIEDMAN: What kind of information -- you
21 mentioned before that some things you can provide and some
22 you cannot because they are confidential.
23 I am not clear on what kind of information would be
24 confidential that you could not provide?
25 MR. SUGUIYAMA: There are certain pieces of
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
85
1 information -- for example, if there is a lot of information
2 about the disclosure of all of the active ingredients, we are
3 precluded under the confidential business information.
4 There might be some specific issues about the
5 combination process or the chemical or how it is formulated.
6 DR. FRIEDMAN: Propriety information.
7 MR. SUGUIYAMA: Yes.
8 Just business related information, but if the issue
9 that we are discussing is a risk or health based issue, EPA
10 has to disclose that information. We have to share,
11 especially with a sister regulatory agency, in this case Cal
12 EPA or CDPR.
13 CHAIRMAN FROINES: Thank you.
14 Paul, how long do you think you will take?
15 DR. BLANC: Fifteen minutes.
16 CHAIRMAN FROINES: I would like to quickly shift,
17 if we can, because Paul has a clinic this afternoon, so, he
18 is not going to be with us, and so, if we can take up his
19 chemicals on the OEHHA.
20 Melanie, I don't know if you want to do an
21 introduction, but if you could hold on the introduction and
22 let Paul talk about the specifics, that would be --
23 DR. BLANC: I would like to start off by seeing if
24 the charge to our group, if I understand it correctly, would
25 be read through the specific chemicals which we were assigned
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
86
1 and to raise questions about the specific studies used or any
2 specific choice in that regard or end points that were not
3 highlighted or addressed or fundamental things that are
4 already agreed upon, ground rules such as the basic
5 assumptions about inter species or availability factors and
6 all of that kind of stuff.
7 Would that be a safe description of what the task
8 is?
9 DR. MARTY: Actually, I would add, in addition to
10 looking at each individual chemical, that we were looking for
11 comment on the methods as well.
12 So, if you have specific issues about the methods,
13 we need to talk about that.
14 DR. BLANC: Then let me start, I would like to
15 start with formaldehyde, among the chemicals that I had,
16 because I think it does raise issues on two fronts, both in
17 terms of the specific studies that were used and the end
18 points, and then on the other hand, it does have an
19 implication, I think, for the overall process, because what
20 you end up with by running through the process as it is
21 delineated is an inhalation reference exposure level that is
22 so low that almost any ambient sampling you could do of any
23 control group would have those exposure levels.
24 In fact, most of the human epidemiologic studies
25 you have cited that the inhalation reference exposure level
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
87
1 is higher than the control group level in the ambient
2 exposures, indoor ambient or mostly --
3 DR. MARTY: Indoor, yes, that would be true.
4 Outdoor, maybe not.
5 DR. BLANC: To me, that highlights that there may
6 be a problem with the construct, because it does not make
7 logical sense then if the purpose of the inhalation reference
8 exposure levels is supposed to be the highlight for the level
9 that we should be contemplating some kind of action.
10 This would be a very back door way of saying that
11 you thought there needed to be action on all indoor
12 environments in regards to formaldehyde.
13 DR. MARTY: There are a couple of things.
14 If you look at the derivation of the REL from
15 Wilhelnsson and Holmstrom, basically in the 1988 study, what
16 we have is a human study.
17 We have as a referent group, a group of office
18 workers that were in the same town in the State government
19 building as the exposed group.
20 The exposed group were folks working at a wood
21 products facility, and there were actually two people exposed
22 to formaldehyde only, and then there were people exposed to
23 formaldehyde plus wood dust.
24 The study measured subjective symptoms through
25 questionnaire and also made objective measurement of nasal
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
88
1 obstruction and nasal mucosal swelling for per second, volume
2 in one second, and a few other measurements.
3 The group of office workers were exposed to a
4 background office concentration of basically 90 micrograms
5 per cubic meter. The exposed workers from the formaldehyde
6 wood plant had statistically elevated symptomology and also
7 subjectively measured nasal and respiratory pulmonary
8 function detriment.
9 So, I think what we can say is that relative to the
10 office workers, these guys showed effects of formaldehyde.
11 What we did was we assumed an eight-hour day, five
12 days a week for office workers, and we made a temporal
13 adjustment of the 90 micrograms to come out to 32 micrograms
14 per cubic meter, and we applied an inter species factor of
15 10, because it was not representative of the general
16 population.
17 So, we come out with a REL of 3 micrograms per
18 cubic meter, and you were correct that it is below what the
19 office workers experienced, but the office workers are not
20 representative of the distribution of sensitivities in the
21 general population.
22 I just had ARB folks tell me what the latest
23 information was on ambient air concentrations, and
24 formaldehyde across the State and between '96 and '98 they
25 averaged between 3 and 4 micrograms per cubic meter, which is
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
89
1 right around where our REL is.
2 DR. BLANC: Outdoor.
3 That is the people's average exposure would
4 probably be more than that, because people's exposure indoors
5 is generally higher than that.
6 DR. MARTY: Right.
7 But I think it is a little bit of a problem to try
8 to say that we have a lot of people exposed at that level,
9 therefore, that is not a good REL.
10 Maybe turn it around and say, maybe we have a
11 problem with formaldehyde exposures indoors.
12 DR. BLANC: That is why I asked the question the
13 way I did, because it is a very back-door way of coming to
14 it.
15 Because actually your data does not support since
16 your control group does not have any symptoms, and if you
17 take the study that you are using, the control group has no
18 symptoms at all at a level which is 30 times higher than your
19 level.
20 DR. MARTY: It is 30 times without the time
21 adjustments.
22 DR. BLANC: I understand that.
23 But one of your problems is that from most of the
24 end points that you are using, not the pulmonary function,
25 although the study, I would say fatally flawed in many of its
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
90
1 analytic approaches, but even if we take it at face value,
2 for the main things that they could find some statistical
3 differences with.
4 In fact, it is very difficult to know that those
5 are chronic symptoms since they are acute symptoms, that
6 nasal irritation which then go away when you are away for the
7 weekend from work, so actually, most of what is analyzed in
8 the study are acute symptoms.
9 DR. MARTY: Acute recurring.
10 DR. BLANC: Acute recurring symptoms without any
11 evidence that it is a cumulative effect, and in fact, every
12 single thing that they analyzed in their study had no dose
13 response in terms of the level of exposure within the
14 exposure site or duration of exposure in terms of years.
15 So, I think that it is a study. Not only that but
16 the control group which they make much of is, has a
17 significant gender difference from the exposure group, from
18 which is 86 percent men, where the control group is 76
19 percent men, also, they state that there is no statistical
20 difference in the smoking preferences, but they never provide
21 the data, because smoking, I think, is going to be so
22 relevant as a potential confounder to the nasal systems that
23 they are focusing --
24 DR. MARTY: They actually have the percentage of
25 smoking in that paper.
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
91
1 DR. BLANC: Well, maybe in the later paper, but
2 they don't in this one.
3 Also, this is a smaller technical thing, but in
4 fact, the paper that you cite in support of the REL -- I take
5 that back.
6 It is really the same study. It is the same study.
7 They just did two separate papers based on the same study. I
8 think that needs to be made a little bit clearer.
9 We are the ones to use it, but actually it would
10 say that -- I don't think this is an appropriate study to use
11 for the end point you are looking at, and because of the
12 problems with formaldehyde and interpreting what is or what
13 is not chronic exposure effect, I think you are really forced
14 to use, this is one exposure where I think you are really
15 forced to use animal studies.
16 I think animal data to the extent that you have
17 them would be more interpretable in terms of a chronic
18 exposure. Without it, it is almost impossible to control
19 those confounders.
20 I mean, you have some ecological studies of people
21 in trailer homes, but once again, comparing people in trailer
22 homes to people in non trailer homes is, with a series of
23 confounders, that I think would be very difficult to control.
24 DR. MARTY: Okay. I must say that use of animal
25 studies may not guarantee that you are going to get a REL
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
92
1 that is higher than the one we just arrived --
2 DR. BLANC: Well, I think it would just be more
3 reasonable.
4 DR. MARTY: You do bring another issue up about
5 whether or not the irritative type of effects measured in
6 this study are chronic effects or are they acute effects.
7 I think we have that same problem with some of the
8 other irritants. It could be that maybe the solution is to
9 not have a chronic REL for those chemicals, where really it
10 is repeated, acute exposures resulting in acute effects.
11 I don't know.
12 The other issue from formaldehyde, though, that it
13 is a sensitizing agent, but that, again, may be considered an
14 acute effect rather than a chronic effect, although it has
15 chronic implications.
16 DR. BLANC: Well, the way I would approach it from
17 formaldehyde, I think that one is primarily interested in, as
18 a chronic effect on the nasal system, but I think that rather
19 than looking at nasal symptoms, which are very difficult to
20 tease out from the acute versus what is an acute versus a
21 cumulative effect, I think to the extent you can look at
22 studies that look at either histological changes or measures
23 of sensation, and there was data about a hyposmia, in the
24 example of the Swedish study, but there was no, again, there
25 was no dose effect and there was no time effect, which it is
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
93
1 really difficult to argue, and no control for smoking for
2 that.
3 That was presented, in the way that you have
4 analyzed it, I did notice that they had another paper from
5 yet the same study, which was histologic effect from
6 formaldehyde alone, and in combination, which was cited as
7 impressive in this reference listing, you have not evaluated
8 at all what seems to me that would be the, as a triad, sort
9 of important.
10 Again, I could see from formaldehyde using
11 primarily animal data and then saying here, here are the
12 histologic studies which are consistent or not consistent
13 with observations in the animal data.
14 But I think just given all these problems in
15 general, I think it would be hard for us find a study that
16 was interpretable, but certainly I don't think that this
17 workplace study is sufficient based on what you have built on
18 it.
19 I just don't think it can sustain the weight of the
20 analysis.
21 DR. MARTY: Okay.
22 But we can look at the animal studies available.
23 Most of them are focused on carcinogenicity, and the non
24 neoplastic lesions were described as plastic, which to me is
25 pretty much the same as neoplastic, or pretty close.
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
94
1 I'm not sure that that is a good end point either,
2 but we can certainly look at that.
3 CHAIRMAN FROINES: Is there animal work on the
4 effects for formaldehyde on asthma and other atopic
5 disorders?
6 DR. MARTY: I'm not sure.
7 We can look at that.
8 CHAIRMAN FROINES: I'm not sure you will get the
9 dose response on that.
10 Do you have any data on IGE responses?
11 DR. MARTY: We would have to look and see what
12 exactly we have as measured with these animal studies we
13 have.
14 DR. BLANC: Just one other general comment on the
15 book is that, based on formaldehyde, but I came across the
16 other places, too, I think that although you put the
17 conversion factor in the physical properties, I think for
18 many of these it would be helpful actually to put in
19 parenthesis following your inhalation reference exposure
20 level, which is in micrograms, to put the PPMs or the PPBs or
21 whatever.
22 DR. MARTY: Oh, you mean up top?
23 Because we do have it in the section delegation
24 of --
25 DR. BLANC: Right.
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
95
1 Oh, I don't know. This is a very small matter.
2 DR. MARTY: No, that is fine.
3 DR. BLANC: So, that is the one that I have the
4 most drastic comments on.
5 I just didn't found that one, I did not think that
6 you could support the conclusions.
7 DR. MARTY: Okay.
8 DR. BLANC: And the logic study they did.
9 So, should I go through the other one's quickly?
10 Can you tell me, I am going to go to chlorine next,
11 some of these had EPA values and some of them didn't, and
12 that was based on whether there was one or there wasn't one.
13 For example, from formaldehyde, there wasn't one;
14 is that right?
15 DR. MARTY: Right, pretty much.
16 But there was one, and whether we thought it was
17 reasonable --
18 DR. BLANC: Well, I think you need to be
19 consistent.
20 You need to cite what it is, even if you don't
21 think it's what you want to use, since you do cite at other
22 places.
23 That was just a question that I had with chlorine.
24 I couldn't tell whether there was -- I was surprised that
25 there was no EPA value for it, but maybe there isn't.
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
96
1 DR. MARTY: Okay. So, in general if there is
2 one --
3 George, just told me that we did cite in the
4 document.
5 DR. BLANC: Maybe that is in the introduction.
6 You say if there is an EPA number, then we cite it.
7 DR. MARTY: Yeah.
8 We actually have it in the table.
9 DR. BLANC: Yeah.
10 I thought that the section on chlorine on major
11 uses and sources was a little bit too telegraphic. I don't
12 think that it needs to be a 10-page description, but it was
13 too telegraphic, and the first sentence is actually very
14 misleading, because chlorine itself is not a common household
15 cleaner.
16 It is chlorine containing or chlorine releasing
17 materials which are common. No one is using chlorine gas to
18 clean their house, but they are using hydrochloride bleach,
19 and I think that pool and recreational water purification is
20 so important that I think it needs to be mentioned.
21 When you say water treatment in chemical processes,
22 I would just include that, and in fact, that chlorine is an
23 integral part of certain bleaching processes, but not many
24 people are using ozone and other things like that.
25 That was just a -- I could not actually see how
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
97
1 this is related to the comment on formaldehyde.
2 I could not see how the chlorine studies,
3 industrial chlorine studies, what they really studied was the
4 outcome of intermittent gases, that is to see high level
5 releases were all relevant to your argument or to the
6 background, so the study from Kennedy, et al, and Chan Young,
7 which is really the same study, are the continuation of the
8 same study, as well as the Quebec study of construction
9 workers, all those were studies which are very interesting
10 and very relevant to intermittent gases, but are not relevant
11 to a chronic low level exposure effect.
12 I think they would be relevant to your acute and
13 exposure documents but I don't think they are relevant.
14 DR. MARTY: So, do you think we should take those
15 out?
16 I think what we will try to do is just put in
17 whatever human data that we found, and some of it definitely
18 is not relevant to a chronic end point.
19 DR. BLANC: Right. Can you clarify for me why, at
20 what point you used the formulas related to extra thoracic
21 respiratory effects or what that means?
22 DR. MARTY: Okay. These are based on the USEPA
23 methodology for looking at human equivalent concentrations,
24 and basically what you are trying to do for this chemical,
25 which is a gas, is look at the relationship between the
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
98
1 minute volume and the surface area of the portion of the lung
2 that is impacted by that chemical between animals and people
3 and are to a human equivalent concentration.
4 So, gases like chlorine, which are reactive, tend
5 to hit the upper airway more than the lower airway, so that
6 is accounted for in their model that is used to look at
7 regional, the RGDR, regional gas deposition ratio,
8 essentially accounts for differential minute volumes, surface
9 areas of the lung region of interest between animals and
10 humans, to get essentially a human equivalent concentration
11 from the average experimental exposure.
12 DR. BLANC: For a lung effect.
13 It has to be a lower lung effect, right?
14 The rationale is that if I give a rat one part per
15 million, and I see an effect in its lungs, the rat is
16 absorbing more than one part per million in their upper
17 airway than the human would at one part per million?
18 DR. MARTY: Actually, you could do it for different
19 regions of the lung.
20 You can do it for respiratory, I should say, so you
21 can look at upper -- the difference between upper airway
22 surface area, if the impact is on the upper airway or you can
23 look at the surface area difference of the deep lung, if the
24 impact is on the deep lung.
25 DR. BLANC: So, for this one, since you were
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
99
1 looking at respiratory epithelial lesions.
2 Therefore, you used a correction that assumed for
3 humans more of the chlorine would get to the lower lung.
4 I just want to make sure I understand what --
5 because it does have a significant effect on the algebra,
6 seems to me.
7 DR. MARTY: Yeah, it does.
8 We are assuming that there respiratory epithelial
9 lesions would also occur in the human, and that is why it is
10 extra thoracic respiratory effect. So, we are looking at
11 comparing the surface areas in minute volumes between the
12 rats, and the surface area being the upper respiratory track,
13 and the people.
14 There is a really big difference in the morphology
15 of the upper respiratory track in particular from rodents to
16 humans, so this is in effect what accounts for dosimetric
17 differences.
18 DR. BLANC: Is anyone else as confused as I am on
19 this?
20 Is everyone following this?
21 I mean, the way to interpret this therefore is
22 that, because what it does is that it adds another factor of
23 10, almost.
24 What you are saying is that the effect that you
25 would see in a rat's lung at one part per million, you would
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
100
1 see in a human at .2 parts per million, because a rat is
2 cleaning out more of the one part per million in its upper
3 airway than the human would?
4 DR. MARTY: No.
5 DR. SALMON: In both cases, the human case and the
6 rat case, you are not looking at the lung effects.
7 You are looking at the upper respiratory tract
8 effects, and the regional gas deposition ratio is an estimate
9 of the extent which the gas is deposited in the region of
10 choice, in which in this case is the extra thoracic region
11 between the two species, but in both cases you are looking at
12 deposition and the effects on the extra thoracic respiratory
13 system.
14 DR. BLANC: Then why does Table 1 talk, focus on
15 the respiratory of the epithelial, which respiratory --
16 DR. SALMON: This would be --
17 DR. BLANC: Nobody reading that would assume that
18 the respiratory epithelial meant the nose.
19 DR. SALMON: That may be in a list of its choice,
20 but we are talking about an extra thoracic effect here.
21 DR. BLANC: See, I would understand your argument
22 if what we were focusing on was the effect of the olfactory
23 epithelial, which may be appropriate.
24 I don't know, because there seems to be an effect
25 there as well.
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
101
1 DR. SALMON: The fact that we are using the extra
2 thoracic RGDR calculation is indicative of the fact that the
3 effect, where we find the most critical concentration
4 dependency is the extra thoracic region.
5 DR. MARTY: In other words, it is more sensitive.
6 DR. SALMON: Yeah.
7 There is probably damage in both areas.
8 But in terms of concentration dependence, the one
9 that the calculations focuses on is the extra thoracic
10 region, because the calculation leads one to conclude that
11 damage is going to occur in lower concentrations in that
12 region, at least in the human case.
13 There are some cases where we actually have effects
14 in both regions, and then what we would then select is the
15 more sensitive site.
16 DR. BLANC: Well, that shouldn't, under section 6
17 then, if they are saying respiratory epithelial lesions, they
18 should say olfactory epithelial lesions?
19 DR. MARTY: Yeah.
20 I think what we are probably trying to do is be
21 inclusive and say, we shouldn't have said olfactory and
22 respiratory to be inclusive of all.
23 DR. BLANC: Well, I know.
24 I think you should say olfactory because that is
25 what you are, unless you go back to the studies and
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
102
1 respiratory doesn't need the lower respiratory tract.
2 You are talking about the cells. Those are
3 certainly in the lower respiratory tract, aren't they?
4 It is not being consistent, I guess. It is fine
5 with me if you use the olfactory.
6 It seems to be a very nice step up of effects.
7 DR. SALMON: I think that the end point of
8 reference, I think the extra thoracic region from the model
9 point of view is more than just the olfactory epithelial.
10 I also agree, I think we need to clarify exactly
11 what was observed and which of the subset of things, which
12 was observed, was actually the subject of the calculation.
13 DR. BLANC: It has a critical effect on your
14 algebra there, right?
15 It basically almost lowers the level by factor of
16 10.
17 DR. SALMON: Well, if you were looking at the
18 effects in the lung as opposed to in your extra thoracic
19 region, you would still have a RGDR, but it would be
20 different.
21 DR. MARTY: So, in other words, there still would
22 be an adjustment.
23 It may not be exactly this number, but it would be
24 close to that number. So, there still would be --
25 DR. SALMON: The human equivalent concentration.
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
103
1 DR. BLANC: Because of the species?
2 DR. SALMON: Yes.
3 DR. BLANC: Because it is a rat?
4 DR. MARTY: Well, there are actually different
5 RGDRs that can be used, and it depends, of course, on the
6 species that was tested.
7 So, if you used a guinea pig or a hamster or a
8 mouse or a rabbit or a rat, you would have different surface
9 areas that plug into the model and different minute volumes.
10 DR. BLANC: I just want to go to one of the other
11 studies where there was, it was also based on animal data,
12 and it was equivalent, so maybe that will be a good example.
13 DR. COLLINS: It was systemic.
14 DR. MARTY: So, right, for non portal of entry
15 effects.
16 There are some in there where the RDGR is assumed
17 to be one for a systemic effect. The actual calculation is
18 to look at the blood gas partition co-efficient between
19 animals and humans.
20 In general, you do not have that information. So,
21 the assumption is that it is the same, that ratio is then
22 considered to be one.
23 I can't think of an example where we actually did
24 have in this group of chemicals data on the blood gas.
25 DR. COLLINS: It would increase three-fold because
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
104
1 of the correction.
2 CHAIRMAN FROINES: Does chlorine become particle
3 associated?
4 DR. MARTY: I don't know.
5 We are assuming it is a gas.
6 DR. BLANC: Can we talk briefly -- are you holding
7 up okay?
8 Hydrogen chloride, now, do you have reason to
9 believe that the biology of the toxicity of hydrogen chloride
10 would be in any way different than chlorine or that it acts
11 any differently in a biochemical ultimate pathway than
12 chlorine gas?
13 I could see that the -- obviously there are going
14 to be a variety of things modified, the net amount that gets
15 to where it is going.
16 DR. SALMON: I think the fact that chlorine is a
17 powerful oxidizing agent, whereas hydrogen chloride the
18 effect is going to be primarily, it would imply some
19 substantial differences in the chemistry there.
20 DR. BLANC: So, you think that the ultimate tissue
21 effect would be different?
22 DR. SALMON: It would probably look somewhat
23 similar.
24 The histopathology is not usually very
25 discriminating to the exact causes of cellular mayhem.
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
105
1 DR. BLANC: Because I can't help but call to your
2 attention to the wildly different values for those two.
3 DR. SALMON: They are chemically very different
4 substances.
5 DR. BLANC: I am not quite sure that they are
6 biologically so very different, ultimately or that ultimately
7 the chlorine that is causing the problem one way or the
8 other.
9 DR. SALMON: I think the toxic agent in chlorine is
10 probably the CL2, at least in the first place and/or various
11 radicals and oxygenated species.
12 Whereas, essentially with hydrogen chloride the
13 first toxic agent is going to be H3O plus hydrogen.
14 DR. MARTY: So, your concern was that the variables
15 are very different?
16 DR. BLANC: Well, .06 micrograms per meter for
17 chlorine, or .02 parts per billion, and for hydrogen chloride
18 in parts per billion or million, it's 5 parts per billion,
19 so, that is -- it is two orders of magnitude different or
20 something.
21 DR. MARTY: In part -- part of the problem with the
22 chlorine RELs, you are starting with the LOAELs, so, you have
23 automatically this LOAEL on certain factors to get to the
24 NOAEL so, that is an issue.
25 DR. SALMON: So, the REL reflects greater
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
106
1 uncertainty?
2 DR. MARTY: Well, actually if you look at the
3 hydrogen chloride, you are also starting with a LOAEL end
4 point.
5 Part of the problem with the paradigm is that you
6 have these uncertainties that you have to deal with. You
7 don't have any way to quantitate them, so you use essentially
8 these uncertainty factors, and sometimes you do get funny
9 results, but I am not so sure that it is such a funny result
10 to have chlorine considerably lower than hydrogen chloride.
11 DR. SALMON: They are different substances.
12 DR. MARTY: Based on their action.
13 CHAIRMAN FROINES: But you are describing the
14 critical effect in both cases as hyperplasia, and Paul, I
15 think, is asking about the methodistic details associated
16 with those, with that end point, do they reflect different
17 methodistic elements, and the answer may not be yes.
18 DR. SALMON: I think the observation of the -- at
19 least the description of the lesions is the end result, which
20 is that something bad is happening in that area of the
21 epithelium, but the process of getting there is expected to
22 be somewhat different because of the different chemistry of
23 the two agents, but the end result is the histopathology
24 typically is not very good at distinguishing the causes.
25 DR. BLANC: Well, yeah, that point is well taken.
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
107
1 I am actually not convinced that, believe it or not
2 is that the mechanism of how chlorine toxicity is still
3 fairly much conjecture in many ways, but I think it is pretty
4 much considered the same for hydrochloride, although it does
5 have pH problems when you get down to the tissue level once
6 you start getting the chlorine there.
7 I am not sure that it is felt to be a particularly
8 different mechanism. The other thing that I would say about,
9 at least maybe the ACL section has to allude to the chlorine
10 gas section, or it is as if these two things existed in
11 parallel universes, and they do not seem to engage very well
12 with one another, these two exposures which I have also
13 viewed as being very closely related mechanistically.
14 DR. COLLINS: Would it be in the body?
15 DR. BLANC: Well, that should be stated.
16 I am not sure that's true, but the other thing is
17 that I think it should be a little bit more explicit here is
18 that in almost any real world way this is encountered, right,
19 it is going to be in an aerosol hydrochloric acid.
20 Basically, I would just comment on that, I would
21 just put a phrase in there so that is clear.
22 Should I break now or --
23 CHAIRMAN FROINES: That question, I was
24 wondering -- well, never mind.
25 You have dioxane and ammonia left to do and
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
108
1 cyanide.
2 Would you like to take those up tomorrow?
3 DR. BLANC: Sure, I have more to say.
4 DR. MARTY: Okay. I did want to make one comment
5 on formaldehyde and whether we should be looking at, well,
6 the background levels are this, and we do not see any
7 effects, the background level in LA is associated with the
8 cancer risk of 35 or 40 in a million, so I think it is
9 problematic to begin with from a carcinogenicity standpoint,
10 and it may also be problematic for sensitive individuals for
11 non cancer end points.
12 So, I just want -- I really hesitate to reject REL
13 because people are exposed to those concentrations and higher
14 anyway.
15 DR. BLANC: Well, I'm just saying that it raises a
16 question about the methodology as it is applied to that
17 particular chemical, because basically if we measured in this
18 room right now, we would be probably way above the REL for
19 formaldehyde.
20 So, how do I base public policy on that kind -- is
21 that going to be -- is the tail going to be wagging the dog?
22 I mean if a REL had such important public policy
23 implications that forces people into a corner of either
24 ignoring the REL selectively or making it your highest
25 priority for any kind of public health action, which I think
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
109
1 would be absurd, also.
2 DR. MARTY: Well, these are in part risk management
3 issues.
4 I mean, they overlap, but they are risk management
5 issues.
6 CHAIRMAN FROINES: That is not an answer to what he
7 said.
8 That point is relevant, but it is not a response to
9 the science.
10 DR. MARTY: In other words, you are saying that the
11 REL to you is not believable because we couldn't measure
12 adverse effects in the control office workers.
13 Actually, you could. That was part of the -- the
14 rest of the problem with that paper, what you are forced to
15 do is look at the initiation of the symptoms and other
16 measured things in this control population, which is not zero
17 exposure, because you can't ever get a zero exposed
18 population for formaldehyde.
19 DR. BLANC: Well, that is why I think for maybe
20 formaldehyde, it makes sense to look at the animal data where
21 you have more, a greater chance of being able to sort out
22 what is going on, I mean aside from the limitations of this
23 particular study, which I think is too flawed to base such a
24 massive leap on.
25 DR. MARTY: It is also interesting to note that the
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
110
1 exposure concentration of those office workers was quite
2 close to our acute reference exposure level.
3 DR. BLANC: It was higher.
4 Oh, your acute reference.
5 DR. MARTY: Right. You are pointing out problems
6 with non cancer risk assessments.
7 There is not a whole lot we can do without a lot
8 more research and looking at the adequacy or validity of the
9 uncertainty factors that are used.
10 CHAIRMAN FROINES: But I think I was going to say
11 this tomorrow or later today, but I think, yes, what you
12 point out is the inadequacies of the safety factor approach
13 to non caner risk assessment.
14 It also is a problem because at a certain degree
15 what you tend to do is you tend to take a lot of studies, and
16 then you go look for the lowest effect level, and you use
17 that to calculate your NOAELs.
18 I think the danger in that is that that leads you
19 sometimes to picking isolated studies, and I think it make
20 more sense at some level to look at the spectrum of studies
21 and look to see how the data are relative, one to the other,
22 and then try and decide what makes the most sense in terms of
23 the consistency of the studies rather than picking the lowest
24 study because you have more confidence, and then I will talk
25 about hexane later, so this is going to come up.
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
111
1 That is probably picking the worst-case example.
2 That case may be at some level a scientific outlier, too.
3 So, whether or not you have sufficient consistency in your
4 studies is an important issue, which may get you a higher
5 REL, but it may get you a better REL.
6 DR. MARTY: We did try to look at studies with
7 respect to the overall database on that chemical and make
8 sure that particular effect has been measured more than one
9 time, or especially in more than one species in terms of the
10 actual concentration that produced the effect.
11 Sometimes the interspecies differences are really
12 pretty big, and, yes, we always take the most sensitive
13 species. We do that.
14 DR. BLANC: Thank you.
15 I will do the others tomorrow.
16 DR. MARTY: Thank you.
17 CHAIRMAN FROINES: Thank you.
18 So, we are going to break for lunch.
19 Be back at two o'clock.
20 (Thereupon the lunch recess was taken.)
21
22
23
24
25
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
112
1 A F T E R N O O N S E S S I O N
2 --o0o--
3 CHAIRMAN FROINES: Why don't we start, Melanie.
4 DR. MARTY: Okay. Peter, will be handing you
5 copies of the overheads.
6 There are a few that I added at the last second
7 from the last June meeting, so some of them you won't have,
8 but most of them you will.
9 I just wanted to go over, that on this document
10 that we are discussing today is one of four air toxic hot
11 spots technical support documents for use in the air toxic
12 hot spots risk assessment program.
13 Again, to go over what we mean by the reference
14 exposure, the concentration at or below which no adverse
15 health affects are anticipated. It is generally based on the
16 most sensitive adverse health effect reported in the
17 literature.
18 It is intended to protect most sensitive
19 individuals in the population. Exceedence of the reference
20 exposure level does not necessarily mean that you would see
21 an adverse health effect.
22 I was asked to talk a little bit about how these
23 reference exposure levels numbers are used, so I am going to
24 talk briefly about the risk assessment method and then about
25 how some of the air districts use the final numbers.
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
113
1 Essentially, what we are looking at is the hazard
2 index approach to evaluating potential non cancer health
3 impacts.
4 For a specific chemical, the hazard quotient is
5 equivalent to the ground level concentration, which in the
6 hot spots program is generally modeled, divided by the
7 reference exposure level.
8 So, if we are talking about chronic reference
9 exposure levels, that ground level concentration is the
10 annualized average.
11 The hazard index is essentially the sum of hazard
12 quotients that affect the same target organ. So, if you have
13 a facility that emits more than one chemical impacting the
14 same target organ, then that facility has to add the hazard
15 quotients in order to get a total hazard index for that
16 target organ.
17 This is just an example of some of the target
18 organs that we have in our document, some of the chemicals
19 impact.
20 This, again, is an example of what you might see in
21 your risk assessment of a facility that emits benzene and
22 1,4-dioxane. You have model ground level concentrations
23 divided by REL, giving you a hazard quotient for each
24 individual chemical, and then if you have CNS effects from
25 both benzene and 1,4-dioxane, you would add those hazard
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
114
1 quotients for the total hazard index.
2 I think this is actually an old example, because
3 the benzene impacts, just for example.
4 DR. COLLINS: These are the numbers that are in
5 effect right now, until the new numbers are approved.
6 DR. MARTY: This comes from the CAPCOA.
7 Next slide, please.
8 So, what happens with the hazard indices, how are
9 those used?
10 For the air toxics hot spots program, the
11 individual air districts are really the implementing
12 agencies, and in the South Coast, their policy is, if a
13 hazard index is greater than five, then they require the
14 facility to do a risk reduction plan, and the purpose of that
15 is to reduce emissions in the long run.
16 If the hazard index is greater than one, then the
17 public notification provisions of the air toxics hot spots
18 act kick in and the facility is required to notify the people
19 living or working in the area of the chemical that is emitted
20 and estimated risks.
21 In the case of facilities that have risk
22 assessments showing hazard indices between .1 and 1, the
23 South Coast just has them in a tracking system where they
24 have, I think it is biannual reporting of the emissions are
25 every four years now, I think, and if it is lower than .1,
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
115
1 then the facility is not tracked at all.
2 DR. GLANTZ: Melanie, what about if they have,
3 let's say .5, for three different organs or something?
4 DR. MARTY: Then they would be in the .1 to 1.
5 It is only per organ.
6 The Bay Area Air Quality Management District has
7 the same policy in terms of risk reduction and public
8 notification, so those are the two biggest districts in the
9 State.
10 CHAIRMAN FROINES: Was that the end of the
11 regulatory discussion?
12 DR. MARTY: Right. That is the end of the slide,
13 so if you want to ask questions about the risk management, I
14 think we should do it now.
15 CHAIRMAN FROINES: Well, let's assume you have a
16 REL that is lower than the ambient concentration of a
17 particular substance, let's say naphthalene 4, the REL for
18 naphthalene 2 parts per billion.
19 Let's assume for some reason it is 3 in LA. What
20 does that REL of 2 trigger, and here we're not talking about,
21 I mean I understand that 2588 hot spots issue because that is
22 very specific.
23 You look at a facility. You look at the
24 exposures -- I mean the air borne concentrations, and you can
25 proceed, but where you have a high ambient level, then what
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
116
1 is the REL?
2 DR. MARTY: Well, I cannot think of any examples of
3 where that was the case for a toxic, but there in the old
4 days we used to also include the ambient air quality
5 standards in the respiratory irritation index, and in the
6 South Coast Air Basin, all of those were above one, and how
7 the district dealt with it, by not requiring facilities to do
8 the notification or risk reduction if the REL, if the
9 background levels were causing the hazard index to be above
10 one, so that is how the South Coast dealt with it for the
11 criteria of the pollutants.
12 CHAIRMAN FROINES: I did not understand what you
13 said there.
14 DR. MARTY: Say, for example, a facility
15 contributed X to nitrogen dioxide and the background was Y,
16 and when you add X plus Y together, it is larger, or much
17 larger than the reference exposure level, which was
18 essentially the ambient air quality standard.
19 The facility was not required to do the
20 notification or risk reduction based on that hazard index.
21 In other words, they took into account in fact that the
22 background was already high and driving the risk.
23 That issue has not come up with non criteria air
24 pollutants, so I do not know what they would do.
25 CHAIRMAN FROINES: So, in Southern California, you
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
117
1 have a lot of refineries, so I don't know, for example, how
2 much hexane is in the air, but you have a relatively
3 conservative REL, and the issue is, once we have approved
4 this document, how does it impact on changing the levels of
5 these air toxics in the ambient environment?
6 DR. MARTY: Well, the way it impacts is if the
7 facility's hazard index is high enough, then they have to
8 conduct a risk reduction on it, and they have to look at
9 their emissions.
10 CHAIRMAN FROINES: But if it is not high enough for
11 ambient, that could theoretically trigger a regulatory action
12 to reduce the levels so that the overall ambient level
13 becomes more healthy.
14 DR. MARTY: It could.
15 The provisions for risk, for notification of people
16 living in your area is enough to drive some facilities to
17 reduce their emissions.
18 CHAIRMAN FROINES: I am talking about being above a
19 Prop 65 number.
20 DR. MARTY: It is not Prop 65.
21 The hot spots provisions program has its own
22 notification revisions.
23 CHAIRMAN FROINES: I'm talking about the ambient
24 concentration of a particular substance is high from a
25 variety of sources, say in Southern California, and you have
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
118
1 RELs, what does it all mean in terms of addressing the
2 ambient concentrations in Southern California?
3 DR. MARTY: Okay. Overall, the whole idea is to
4 reduce emissions from stationary sources in this program.
5 So, it would drive reductions and emissions if they
6 were exceeding the REL by a certain amount. In this case, it
7 would be five in the South Coast.
8 CHAIRMAN FROINES: I keep asking the same question.
9 You keep giving me a different answer. I keep
10 saying, what if the individual facility is below the high
11 number but is still contributing to the overall concentration
12 in the basin that is above the number?
13 DR. MARTY: Okay. Sorry.
14 So, you have a concentration that is higher than
15 reference exposure level, that's, quote, ambient for
16 background.
17 Is that the scenario?
18 Okay. Then you have a facility, there is no impact
19 because unless that hazard index exceeds a certain amount
20 from the facility itself, there will be no consequence.
21 So, in other words, each facility is looked at
22 essentially in a vacuum. What we tried to do was have for
23 the criteria air pollutants, since we knew they were a
24 problem in the South Coast Air Basin, they have the facility
25 contribution somehow be evaluated, but people on the front
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
119
1 lines of implementing the program do not like that.
2 So, we don't do that anymore. We don't include
3 background. In fact, we don't include criteria air
4 pollutants at all in the hot spots program any more.
5 So, it is a similar situation.
6 DR. ATKINSON: It would be even worse for
7 formaldehyde, which is largely in the air in the complex.
8 DR. MARTY: For formaldehyde, it has really only
9 been a driver from wood products facilities.
10 DR. ATKINSON: In LA, it is about 80 percent comes
11 from atmospheric information.
12 DR. GLANTZ: Would it be correct to say that what
13 you are saying is, when you look at the hazard indexes for a
14 given plant, you look at what they are contributing above the
15 ambient levels; is that right?
16 DR. MARTY: Actually, you would just look at what
17 they are contributing in and of themselves not relative to
18 ambient.
19 So, if there is already an existing hydrochloride
20 acid, for example, and a facility, say combustion sources is
21 emitting hydrochloride acid into the combustor, the only part
22 of that total that is looked at is the facility's
23 contribution in terms of risk management.
24 CHAIRMAN FROINES: What I understand is if a
25 facility has a concentration that is above the REL, then
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
120
1 something can happen.
2 If the facility is only contributing a certain
3 percentage of the ambient concentration as above the REL,
4 nothing happens.
5 DR. MARTY: That is right.
6 CHAIRMAN FROINES: Well, I think that is absurd.
7 DR. COLLINS: I don't think completely, but it is
8 changing.
9 First of all, there is an environmental justice
10 initative in the South Coast where they are looking at
11 cumulative impacts, and they are also starting another air
12 toxics reduction plan in addition to this.
13 I think you are right, under hot spots there is no
14 current driver now, but I think there are other things that
15 are occurring to drive that, to answer that kind of question,
16 especially --
17 DR. MARTY: Jim, I think the issue is, it is a risk
18 management problem.
19 We don't really have anything to do with how the
20 districts actually implement that program.
21 CHAIRMAN FROINES: I'm only asking the question,
22 because we sit here and spend hours and hours and hours going
23 through hundreds of chemicals, and then say, what is the
24 impact of doing that, and you say the answer is none.
25 DR. MARTY: No, no, I do not think that the answer
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
121
1 is none.
2 CHAIRMAN FROINES: In terms of the contribution to
3 ambient air quality, I think I am right to say that, in terms
4 of hot spots, then, yes, there is --
5 DR. MARTY: Okay. Then you are differentiating
6 between near source exposures.
7 If the facility is emitting above the REL, it would
8 be reduced by risk management efforts.
9 CHAIRMAN FROINES: But the notion of 1807, was to
10 address the ambient air quality and 2588 came in later.
11 So, in terms of 1807, we have a gap between the
12 finding of these kinds of values and then what subsequently
13 occurs to reduce the contributions in the ambient environment
14 to those substances.
15 In other words, these RELs won't trigger the
16 adoption of best available control technology which is stated
17 in 1807 based on a less than -- based on a release rate of
18 less than that, which would exceed the REL.
19 DR. MARTY: Correct.
20 On a facility by facility basis, that's right. But
21 if your major source of chemical is stationary sources, and
22 they are exceeding the REL in a hot spot or near source
23 environment, you will get eventually overall ambient
24 reductions.
25 CHAIRMAN FROINES: When we did benzene, for
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
122
1 example, then the risk managers go out and they try to look
2 at emission sources, and they try and see how to adopt best
3 available control technology for benzene that we have
4 declared a toxic air contaminant, right?
5 That is what they do.
6 They don't look at necessarily at anything, but how
7 can we reduce the benzene from a refinery or from solvent
8 plant or whatever?
9 DR. MARTY: I think ARB may be better able to
10 answer that question.
11 I think it is true that the hot spots program
12 really is focusing more on community risks rather than
13 overall regional basin risks.
14 DR. FRIEDMAN: One thing that confused me a little
15 bit was that if something got over one, the public was
16 warned, but it took to get over five before anyone was going
17 to do anything about it.
18 That does not seem to make sense to me. If it got
19 to the level where the public was notified, the public would
20 want you to do something about it at that level.
21 DR. MARTY: Well, in practice, that is kind of what
22 happens.
23 Most facilities don't want to have to go through
24 the public notification, so they will and they have
25 voluntarily reduced emissions.
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
123
1 Again, this is something that was the South Coast
2 Air Quality Management District's policy. So, it was created
3 by their staff and adopted by their Board.
4 Okay. There were basically two things that I
5 wanted to cover in the presentation. Some of it I just
6 labeled unfinished business from the last June meeting where
7 there were issues that Panel Members expressed concerned.
8 Basically, I pulled four out of the transcript that
9 seemed to cause the most heartburn. One of them was
10 definition of chronic exposure, and also, I might tag into
11 there, use of intermediate uncertainty for sub chronic to
12 chronic extrapolation.
13 Another was the criteria to use an intermediate and
14 uncertainty factor of three for LOAEL to NOAEL extrapolation,
15 and then the third one is formaldehyde, which we talked about
16 a little bit already.
17 The question back then was our NOAEL really a
18 LOAEL, and the discussion has turned on a foot on that
19 chemical, and then the final one, is hyperplasia a low
20 severity effect?
21 I thought I would just go through each one of those
22 with a potential change or solution.
23 The first one, in terms of definition of chronic
24 exposure, in our document we described chronic exposure as
25 exposure that is greater than 12 percent of the lifetime.
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
124
1 So, that applies to all toxicology studies, rats,
2 mice, rabbits, etcetera: If it is greater than 12 percent of
3 the lifetime, we consider it a chronic toxicity study, and it
4 also applies to human occupational studies, when we use them,
5 if it is greater than 12 percent of the lifetime, which is
6 essentially eight years based on a seven-year lifetime, then
7 we consider that chronic exposure, and this of course, is
8 then related to whether or not you use an uncertainty factor
9 to extrapolate from a sub chronic study to chronic exposure.
10 Some of the issues that came up is, well, what if
11 the chemical has a long half-life or bioaccumulates or the
12 effect you are looking at is progressive or accumulative and
13 not reversible, isn't that a problem to have chronic defined
14 as greater than 12 percent?
15 So, a potential solution that we thought was
16 perhaps to use a subchronic uncertainty factor of 10, even
17 when the exposures are greater than 12 percent of a lifetime,
18 if those things apply to that study and that chemical.
19 DR. GLANTZ: One question I had about this, when I
20 was reading the report, you do timescaling in terms of dose.
21 If you have an experiment which is, say, 12 percent
22 of the lifetime, do you just consider that level to be -- you
23 have got some animals in a cage, and you have exposed them to
24 some concentration for 12 percent of their lifetime, is that
25 then the concentration that you use, or do you say, okay,
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
125
1 let's not extrapolate that out of the rest of their lifetime?
2 DR. MARTY: That is the concentration that we use.
3 DR. GLANTZ: So, if it less than 12 percent, then
4 you do a time adjustment?
5 DR. MARTY: If it is 12 percent or less.
6 DR. GLANTZ: Okay. Let's say that I did it for six
7 percent of their lifetime, and would you then do your time
8 adjustment to get up to 12 percent or to get up to the whole
9 lifetime?
10 DR. MARTY: Well, what we would do is use a
11 subchronic uncertainty factor of 10 in that case.
12 DR. GLANTZ: Okay. But then how does that relate
13 to the time, or do you just use, because that was one thing
14 I got a little confused by, do you just deal with the
15 subchronic things, so you do not do a time adjustment, and
16 you just put an uncertainty factor in; is that right?
17 DR. MARTY: If it was, for example, eight hours for
18 24 and five days a week, if that is what the exposure regime
19 was.
20 DR. GLANTZ: For 12 percent of the lifetime.
21 DR. MARTY: Right.
22 We would consider that. We would multiply by 8/24
23 and 5/7 to get the concentration that would be the point of
24 extrapolation.
25 If the exposures were greater than 12 percent of a
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
126
1 lifetime, if they were less, we would then add an additional
2 uncertainty factor of either 3 or 10, depending how much less
3 than 12 percent it is.
4 DR. GLANTZ: I see. Okay.
5 So, basically what you were doing, so the time
6 extrapolation that you did was to go from whatever period the
7 experimental exposure was to assume you would spread it out
8 over the whole day, basically, and then if you had a
9 subchronic experiment, and then you would deal with that, not
10 with the time extrapolation but by putting in an uncertainty
11 factor, that I was a little confused by that.
12 DR. WITSCHI: I was wondering where this comes
13 from.
14 I think the differentiation and the chronic and
15 subchronic studies really comes from the early days,
16 particularly drug testing, and if I recall correctly, the
17 common risk was, if you did not see any toxic effects at any
18 given level for 90 days, there is really no point in going
19 any further, because you would not see them if you go longer,
20 with the exception of cancer.
21 So, it is not really so much, some think it has to
22 do with time, but really what you are looking for, and 90
23 days is generally accepted, as I said, if you don't see any
24 effects, there is no need to go further, because 180 days
25 wouldn't show anything either.
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
127
1 I guess that is where that comes from.
2 DR. MARTY: That is where it comes from,
3 essentially.
4 I guess we thought about it, which is why we're
5 recommending to you an uncertainty factor, even if it is
6 greater than 90 days.
7 DR. WITSCHI: Well, wouldn't it be so if you had 90
8 day studies, no observed effect level, you could say if you
9 would have exposed them for 180 days, a year, two years, you
10 still wouldn't see an effect, except cancer?
11 DR. MARTY: We would still apply a subchronic
12 uncertainty factor, even if we started at a NOAEL.
13 DR. WITSCHI: Do you know of any agent which is not
14 in effect during a 90-day exposure but which then has one for
15 cancer, after one-year exposure?
16 DR. SALMON: I think what you are saying is 95
17 percent of cases that is undoubtedly the way you have
18 described it is exactly where this idea comes from, from
19 choosing 12 percent of lifetime as the minimal definition of
20 a chronic exposure, but there are agents for which this might
21 not be true.
22 For the sake of argument, if we were looking at
23 something, let's say 1,4-dioxane, it is possible to enlist an
24 experiment where the dose given was such that it would
25 accumulate not quite to the point of seeing specific toxic
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
128
1 points within 90 days, but it might reach that point within
2 180 days.
3 Obviously, that is an exception situation.
4 So, I think we are saying for most situations this
5 would not be something that would happen. There may be cases
6 where in exceptional circumstances the analyst would want to
7 use their expert judgment to put in an uncertainty factor
8 reflecting long times of bioaccumulation or progressive and
9 reversible effects, but this would be an exception rather
10 than the general principle.
11 DR. MARTY: I think one thing I can think of that
12 would be considered a progressive and not reversible effect
13 would be fibrotic disease.
14 CHAIRMAN FROINES: What do you mean when you say
15 that?
16 DR. MARTY: Well, an example that I think of is
17 emphysema.
18 You may have emphysema from cigarette smoking. If
19 you remove cigarette smoke, you still have emphysema, and it
20 still progresses, and that is just an example of a toxic
21 affect that is progressive, even among cessation of exposure.
22 I mean, it is not particularly applicable in terms
23 of subchronic, because -- well, I don't know how long you
24 have to smoke before you see emphysema, but maybe Dr. Witschi
25 does.
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
129
1 DR. KENNEDY: It depends on the severity of the
2 emphysema and the amount of smoking and a host of other
3 factors.
4 Most of these people get continued lung destruction
5 because the entire elastic structure of the lung is gone.
6 DR. WITSCHI: Yeah, but such for somebody who
7 smokes for ten years, he has already compromised lung
8 function.
9 So, you do not need to smoke for a lifetime. You
10 only need to smoke for a few years. Then you already know if
11 you have compromised lung function.
12 DR. MARTY: Okay. We were going to propose using a
13 subchronic uncertainty factor, even if it was by definition
14 of chronic exposure, if we had this problem of the
15 pharmacokinetic problem here, where if the chemical really
16 has a long half-life, a short exposure actually results in a
17 chronic exposure.
18 The good example is lead. If you have a subchronic
19 exposure to lead being stored in the bones, you eliminate the
20 exposure, but you still have a constant level of exposure to
21 lead as it comes out of the bone.
22 So, that is one kind of chemical where if you had a
23 chronic exposure that was by definition chronic, in addition
24 still want to have an uncertainty factor.
25 I don't know if we need to do that.
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
130
1 DR. KENNEDY: When they are described as the
2 situation rather than placed in an entire category.
3 DR. MARTY: You know, that is a good question,
4 because I have looked through this first set of 40 chemicals,
5 and the only ones that I could really come up with where the
6 effect might not be reversible, were manganese and mercury
7 neurotoxicity, but I may be wrong about the reversibility or
8 the extent of the reversibility.
9 DR. KENNEDY: That in turn may have a bearing on
10 the end organ response rather than the nature and duration of
11 the toxicity.
12 DR. MARTY: Right.
13 Another potential example is hexane, which we are
14 going to talk about in a minute anyway, that the peripheral
15 neuropathy produced by hexane is very slowly reversed.
16 I do not know how long an exposure a person needs
17 to get that peripheral neuropathy, but it is not what you
18 would call readily reversible.
19 Anyway, it is too bad that Dr. Blanc left, because
20 he is the person who raised the issue initially.
21 CHAIRMAN FROINES: So, you are suggesting what with
22 hexane?
23 DR. MARTY: Well, I am not suggesting anything with
24 hexane.
25 I was just thinking of another example where the
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
131
1 toxic effect is not particularly reversible. I do not know
2 if you would want to add, I think, actually in this case our
3 hexane number is a USEPA, so it is not a moot point.
4 CHAIRMAN FROINES: We will get to hexane, because I
5 am not very happy with that number.
6 DR. SALMON: The issue, basically, is where you
7 have something potentially, at least is going to accumulate
8 over a very long period of time either because of the
9 pharmacokinetics or because of the relatively reversible
10 peripheral neuropathy, that due to that accumulation, your
11 NOAEL for 90 days might not be a NOAEL.
12 After 180 days, you might, in fact, have an
13 observable effect on 180. I think we are saying this would
14 be an unusual situation, but we proposed putting the extra
15 qualification in to accommodate the possibility that we might
16 find such an unusual situation.
17 CHAIRMAN FROINES: Well, I guess my objection is,
18 I'm a bit little concerned about making public policy on the
19 basis of the outliers, and I would rather that you didn't
20 make the adjustment, except where you identify cases where it
21 is particularly relevant.
22 DR. MARTY: That is what you are proposing.
23 We are not proposing just to slap this on to all
24 the chemicals. Look at the document. It really would be
25 only a very few chemicals that would qualify for that.
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
132
1 CHAIRMAN FROINES: I think it has to be used very
2 judiciously.
3 DR. MARTY: I would agree.
4 Jim, next slide please.
5 At the last June meeting when we were talking about
6 our criteria for using modified uncertainty factor of 3
7 rather than 10 to extrapolate from a low observed adverse
8 level to a no observed adverse level, some of the Panel
9 Members brought up that they didn't like the incidence of 50
10 percent or less than 50 percent as part of the criteria.
11 Essentially, the criteria, if it is a mild effect
12 based on USEPA's severity categories, which are described in
13 our document in the methodology section, and if the incidence
14 is less than 50 percent, and I think several of the Panel
15 Members thought that was too high of a number, when you think
16 of terms in epidemiology, something that happens to 50
17 percent or 45 percent of the people, it sounds like a
18 horrendous and catastrophic effect.
19 I'm suggesting a potential change to that criteria
20 to have an UF of 3 if the effect is mild and incidence is
21 less than 25 percent.
22 That may still sound like a big number, but when
23 you are talking about the types that we use, it is hard to
24 see much less than that.
25 For example, if you have a sample size of 10 in the
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
133
1 controls, and 10 treated animals, and you have a zero out of
2 10 incidence in controls, you need a 3 out of 10 incidence in
3 the animals in order to be statistically significant at P
4 less than .05.
5 So, I didn't want to make that number too much
6 lower, because you would really be running into the no
7 observed adverse effect level as defined by the animal
8 experiment.
9 So, this may help a little bit. It still sounds
10 catastrophic in terms of epidemiologic effect, and it only
11 concerns mild effects, not anything that we would consider a
12 severe effect.
13 CHAIRMAN FROINES: Go ahead, if nobody jumps on
14 you.
15 DR. FRIEDMAN: Excuse me, that is 3 instead of
16 what, 10 or zero?
17 DR. MARTY: It is out of 10.
18 Is hyperplasia a low severity effect?
19 This is another thing that was discussed in June.
20 I do not have any ready solutions.
21 I think that it was essentially brought up when we
22 were discussing the propylene REL where hyperplasia was noted
23 and is the critical adverse affect, but propylene is not a
24 carcinogen.
25 So, hyperplasia is sometimes a normal response.
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
134
1 For example, physiologically to hormones, there is a lot of
2 examples of hyperplasia, that's normal.
3 In terms of propylene, it's a response to the
4 inflammation. There are actually about seven or eight
5 chemicals that we have used, and it is based on hyperplasia,
6 where they are not carcinogens.
7 So, I think in terms of reversibility, this may be
8 an issue.
9 Is that hyperplasia reversible or not, and we are
10 certainly trying to distinguish between hyperplasia and
11 dysplasia and neoplasia.
12 So, I don't have a ready response to that, and
13 actually I need to step back a second.
14 We are calling it a low severity effect, because we
15 are following the USEPA guidelines on severity effect, and if
16 there is no concomitant change in organ weight, but we do see
17 hyperplasia, they consider that a mild effect rather than
18 severe effect.
19 So, that is what the issue is. I thought we could
20 elicit the expert opinion of Dr. Witschi, if you can weigh in
21 on his idea of hyperplasia.
22 DR. WITSCHI: I have to agree with that,
23 hyperplasia is a quite normal response, or something that is
24 there like -- it simply means like more cells, but it by no
25 mean means that the changes are reversible.
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
135
1 It can convert to normal one's. I think the
2 problem comes when it turns into something that leads to
3 uncontrolled growth, and there, again, you said it, it is
4 either in dysplasia or certain -- which is an indicator of
5 this, that it actually does not want it to have.
6 DR. MARTY: We have a couple of examples where we
7 used hyperplasia as the end point for the chronic REL, and
8 the chemical happened to be a carcinogen.
9 Now, maybe you want to comment on that, if you
10 think that is not really a good thing or because it is a
11 carcinogen, you know it has the potential to progress to
12 dysplasia or neoplasia, is that a problem?
13 Maybe Dr. Kennedy can weigh in on that.
14 DR. KENNEDY: I have a problem with that.
15 Perfectly normal appearing histology with
16 hyperplasia in the breast, and clearly that represents the
17 histology and the mammographic finding which is associated
18 with the risk of malignancy, polyps in the large bowel,
19 histologically are not dysplastic, and after a long delay of
20 ten years, significant percentage of those people become
21 malignant.
22 I hear that you sort of get back into the time
23 factor and the subchronic problem that you had before.
24 Again, it depends on very much the circumstances of the
25 individual observation.
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
136
1 DR. WITSCHI: They may go in different directions.
2 You just said, how we are dealing with the
3 carcinogen, the uses of hyperplasia, and how do you know it
4 is a carcinogen?
5 DR. MARTY: From NTP bioassayas.
6 DR. WITSCHI: Okay. That is a no-brainer, because
7 this is something that produces hyperplasia led to cancer,
8 that is how you know it is a carcinogen.
9 So, saying what are we doing in the carcinogen that
10 causes hyperplasia?
11 DR. BYUS: That is not completely true.
12 Tumor promotion, the classic tumor promoter, as
13 opposed to an initiator or complete carcinogen, like
14 phorbolester is one of them, phenobarbital that causes
15 hyperplasia, are not carcinogenic at all.
16 Yet if you combine them with a carcinogen, if you
17 have a mutated cell there, the hyperplastic stimulus to the
18 mutated cell which has been muted by initiating, let's say,
19 or radiation, or whatever, will increase the likelihood
20 significantly of it becoming a tumor.
21 Yet, it did not cause the initial mutating event.
22 That is what the tumor promotion is as distinct from complete
23 carcinogen or initiation.
24 So, in a sense, it could be. Everyone is exposed
25 to carcinogens. So, if you had a pure hyperplastic stimulus
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
137
1 that was not a complete carcinogenic agent at all, it could,
2 in fact, be a risk, yes.
3 Estrogen risk is due to hyperplastic stimulus that
4 it constantly supplies the epithelial cells, not to itself is
5 an initiated agent or muted agent. So, it could be, I am not
6 saying it is a good thing to be constantly exposed to
7 hyperplastic stimulus by a toxic agent, depending upon where
8 you were getting the hyperplasia, where there was likelihood,
9 if it was in some epithelial cell where there is likely to be
10 a lot of initiating, this is how I would look at it, you
11 would not want to be exposed to it, I don't think.
12 DR. MARTY: That is a good point.
13 DR. BYUS: It would be a combination effect with
14 another agent, or another chemical in this case.
15 What you are saying for the single chemical is
16 true, in and of itself would not be a risk, but everyone has
17 initiated cells everywhere caused by other agents and other
18 phenomenon.
19 That is the classic story of tumor promotion that
20 is very well accepted these days.
21 DR. MARTY: I think that, if you think about what
22 EPA had done and what we had proposed to do, the type of
23 hyperplasia that we are talking about is very mild.
24 When you grade it histologically on a scale of
25 five, it is one that they are talking about. You have to be
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
138
1 real careful how you --
2 DR. BYUS: The realm of multiple chemical
3 exposures, I personally don't think it's typically a good
4 thing.
5 I sense in a population base it may, the problem is
6 that there is not good ways of evaluating tumor promotion.
7 EPA doesn't deal with it too well. Most people don't talk
8 about tumor promotors as distinct from complete carcinogens.
9 So, that really is one of the problems.
10 DR. MARTY: In the case where we used hyperplasia
11 as an end point, it was the most sensitive end point for that
12 chemical.
13 We actually have chlorine, hydrochloride, hydrogen
14 sulfide, methyl bromide, naphthatlene and propylene are the
15 chemicals, and propylene is where it came up last time, when
16 we were talking about propylene.
17 DR. KENNEDY: In what cell system?
18 DR. MARTY: It is all olfactory or upper
19 respiratory tract.
20 CHAIRMAN FROINES: Well, leaving aside the issue of
21 cancer promotion, you are defining hyperplasia as a mild
22 effect?
23 DR. MARTY: As long as there is no organ weight
24 change associated with it, that was the EPA classification,
25 otherwise they popped it over into severe.
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
139
1 CHAIRMAN FROINES: What occurs upon removal of
2 exposure?
3 DR. MARTY: Well, that is the question.
4 That is where I think reversibility is an issue.
5 If it is reversible, then I would consider it a more mild
6 effect than if it is not reversible.
7 DR. KENNEDY: You are certainly more likely to see
8 that in the olfactory than in the respiratory, I would guess.
9 DR. MARTY: So, right now we are still calling low
10 grade hyperplasia a low severity effect.
11 CHAIRMAN FROINES: Low grade hyperplasia, you are
12 calling, you are calling it --
13 DR. MARTY: Low severity effect, a mild effect.
14 CHAIRMAN FROINES: What would you do, Peter?
15 DR. FRIEDMAN: On the elicited expert opinion, are
16 you saying that for each particular chemical you will get an
17 opinion as to whether the hyperplasia in that instance is
18 serious or not, or you saying you are just trying to get
19 expert opinion about the whole general concept?
20 DR. MARTY: Thinking about the whole general
21 concept, and actually there are a couple of experts among you
22 guys, and I was trying to hear what you wanted to say and if
23 you thought maybe it was a topic that we could do some --
24 DR. WITSCHI: The study, you know, how do we know
25 it was reversed, unless you do the experiment, you cannot
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
140
1 tell from looking just at the slide, one time in point after
2 so and so many exposure, everything is going to go, whether
3 it is going to disappear or whether it is going to progress.
4 You just can't tell.
5 DR. MARTY: You need studies where they did serial
6 sacrifice after cessation of exposure.
7 DR. BYUS: The more I think about the tumor
8 promotion aspect, I would be mostly concerned about where, if
9 it was the nasal, whatever, where there is less likely to
10 have a tumor and develop into cancer, I would be less worried
11 about it there than some other site, maybe the lung
12 epithelial I would be more worried about.
13 So, from the tumor promotion point --
14 CHAIRMAN FROINES: Roger, what is the --
15 DR. WITSCHI: Not necessarily, no, no, no, no.
16 Now you see it in the rats. You may see in the
17 people deep down.
18 DR. GLANTZ: Could you explain that for those who
19 aren't toxicologists?
20 DR. WITSCHI: Well, rats are obligatory nose
21 breathers.
22 So, a lot of the changes you see in their nasal
23 epithelia are simple, because that is where the stuff goes
24 through and has concentration.
25 People to some extent breathe also by mouth, and so
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
141
1 the passages of the nose might be bypassed, but certain
2 agents may produce any changes in the deep lung.
3 DR. GLANTZ: So, you are saying that the rat nose
4 is in some way a surrogate for human lungs, to simplify it?
5 DR. WITSCHI: The other one is you know about the,
6 I know we are not dealing with carcinogens, but the general
7 consensus is that there is no organ specificity in the
8 carcinogens, I mean if agent X produce in the rats tissue X,
9 doesn't mean it is going to happen in man.
10 DR. BYUS: Promotion, I am not sure works exactly
11 that way as sort of initiation.
12 My feeling is that there is more tissue
13 responsiveness to promotion than there is to initiation, but
14 I don't know that. That is just a feeling.
15 There is probably data about that. I just don't
16 know.
17 CHAIRMAN FROINES: Do you know what the ambient
18 concentration of naphthalene in the LA basin is?
19 DR. ATKINSON: The highest number I have seen is
20 two PPB -- no about one -- so there was six micrograms per
21 cubic meter.
22 CHAIRMAN FROINES: This is a relevant issue,
23 because their naphthalene number is two PPB for hyperplasia.
24 I mean it is like we are driving these numbers
25 down, these RELs are so low for highly, highly uncertain
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
142
1 health end points, that it makes the whole thing have no
2 meaning at some level.
3 Olfactory epithelium metaplasia, hyperplasia from
4 naphthalene in the ambient air basin in Southern California
5 in two parts per billion, which is the ambient level or
6 almost the ambient.
7 DR. ATKINSON: Average may be a factor of five
8 down.
9 CHAIRMAN FROINES: So, we are all really in the
10 same ballpark with what everyone in LA is breathing.
11 DR. ATKINSON: The UCR entomology museum, we
12 measured half a PPM in naphthalene, and people have been
13 living in that place for ten years, five days a week, and
14 they were still living -- some seemed to be.
15 CHAIRMAN FROINES: The one's that stopped coming to
16 work.
17 DR. MARTY: Has any one looked at their nasal
18 epithelium?
19 CHAIRMAN FROINES: The point is that you ended up
20 with .002 parts per million on naphthalene, and it begins,
21 you have to say, is this an end point that we really need to
22 take seriously for a REL?
23 I don't know. It seems somewhat questionable to
24 me.
25 DR. MARTY: In some cases, it is the only effect
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
143
1 noted.
2 So, I don't know.
3 CHAIRMAN FROINES: That's the point.
4 It makes more sense to pick an end point that has
5 potential consequences. I mean I would look at the rat data
6 on cataracts, for example, and see what that looks like for
7 calculating the number, but that is the problem to get into
8 is you start to get numbers so low that you have to question,
9 the meaningfulness of this.
10 DR. MARTY: The other issues is if you ignore the
11 hyperplasia as an end point you may end up with a REL that is
12 way above you, the concentration that causes hyperplasia in
13 experimental animals, and then where have you gone?
14 CHAIRMAN FROINES: We are not talking about
15 carcinogenisis here, we are talking about hyperplasia and
16 nasal cavity from irritation.
17 DR. MARTY: Right. Then you are no longer
18 protecting against that effect, if you don't think that
19 effect is adverse, that is one thing, but if you think that
20 is an adverse effect, you need to be careful on how far you
21 go up above that, that is just all I'm saying.
22 CHAIRMAN FROINES: That is not clear to chronic
23 effect.
24 DR. WITSCHI: Where from the EPA has the
25 classification been serious and not so serious effects?
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
144
1 DR. MARTY: We have it in our documents, it is a
2 table.
3 DR. WITSCHI: Yeah, but what is their reference.
4 They did not invent it either?
5 DR. MARTY: USEPA, 1994.
6 DR. GLANTZ: He is asking where did they get it
7 from?
8 DR. WITSCHI: Where is this table in your document?
9 DR. MARTY: It is on page 18.
10 It comes from their, USEPA document describing the
11 derivation of inhalation reference exposure levels.
12 DR. WITSCHI: Did they invent it?
13 See, the reason that I am asking this, the only
14 really serious attempt to write those things up was published
15 in what used to be the American Journal for Respiratory
16 Disease and American Lung Association, and they put together
17 a table of anything from mild to serious health effects, but
18 this was really designed to produce some uniformity in the
19 analysis of epidemiological studies.
20 It did not necessarily have much to do with reality
21 and cannot necessarily be translated to what we see in
22 toxicology studies in animals. This was a classification of
23 terms in different findings.
24 MR. LEWIS: Dr. Witschi, USEPA adopted their table
25 from a paper from De Rosa, 1985, and Hartung, 1986.
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
145
1 DR. WITSCHI: Sorry, can you say that, again?
2 MR. LEWIS: De Rosa, 1985, the paper was titled,
3 Ranking Chemicals Based on Chronic Toxicity Data.
4 I am not sure we cited those papers. It is cited
5 in USEPA's document, 1994. USEPA cites the papers that I
6 used.
7 CHAIRMAN FROINES: We have to move on.
8 DR. MARTY: Okay.
9 I was thinking we could add more text to our
10 document, describing the pros and cons of looking at
11 hyperplasia as an end point and defining it as mild or
12 severe, if that would be useful.
13 The next thing that I wanted to talk a little bit
14 about was the second round of public comments and the
15 comments that we got from people in that second round, and
16 also stir in some of the comments that we got from the first
17 round that are critical comments and resulted in a change in
18 the reference exposure levels.
19 Essentially for round two of the public comment, we
20 got comments from the Chloropicrin Manufacturers Task Force:
21 On the methodology from Elizabeth Margosches. She happens to
22 work for USEPA, but she was not representing USEPA.
23 She is a statistician. From the Metal Finishing
24 Association of Southern California: From the Chemicals
25 Manufacturers Association, Glycol Ethers Panel: From Wilmer,
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
146
1 Cutler and Pickering on nickel: From the CMA Phthatlate
2 Esters Panel on DEHP: And from Eastman Chemical, represented
3 by McKenna and Cuneo, on DEHP.
4 I obviously did not pick out every single chemical.
5 I just picked out ones that seemed to have some importance.
6 The Chloropicrin Manufacturers Task Force asked
7 that we distinguish between the most sensitive effect
8 reported and most sensitive relevant adverse effect, and we
9 do think that we used the most sensitive relevant adverse
10 effect.
11 Although this discussion of hyperplasia is sort of
12 an example of that. They also requested that we use
13 benchmark concentrations in estimating risk from experimental
14 data, and this is something also that the Panel talked about
15 before, and we really did not do much benchmark dose work for
16 the chronic RELs.
17 Part of the big problem is that USEPA and other
18 folks have not really come to consensus on the methodology.
19 One example of lack of consensus is whether you use 10
20 percent response rate as your benchmark concentration or five
21 percent response rate. We are not very comfortable using the
22 benchmark concentration for 10 percent response rate, but
23 that is currently what EPA is doing.
24 So, that is just one example of that problem,
25 problem coming to consensus on the methodology following,
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
147
1 there is one or two RFC that we proposed adoption that use
2 the benchmark, dosimeter. We used the USEPA's 1994 document
3 methods for derivation and inhalation reference concentration
4 and application of inhalation dosimetry, and we didn't feel
5 that we should go back and try and reinvent the wheel or
6 change that too much.
7 So, we have not complied with this request.
8 They commented that the overall methods were not
9 really appropriate for local, reversible and
10 receptor-mediated responses, because those types of responses
11 they did not consider adverse.
12 We disagreed. We do not think because it is a
13 local, reversible or receptor-mediated that it is not
14 adverse. An example is irritation mediated by the lingual
15 nerve.
16 CHAIRMAN FROINES: This is appropriate to
17 hyperplasia as well?
18 DR. MARTY: It is reversible and it is local.
19 Another comment they, that they did not think that
20 the intra species uncertainty factor that we applied for
21 sensitive human population, sensitive human subjects in the
22 population is justified for non progressive, non specific
23 irritation at the portal of entry, and we have a lot of
24 examples of that, of formaldehyde, and HCL, chlorine.
25 We disagree in that we think that humans do vary in
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
148
1 their response irritants. There is some indication of that.
2 If you look at the entire data base for
3 formaldehyde, there are people who have a quite a wide
4 variability in response to the irritation, and we did not
5 feel that there was scientific support for those comments and
6 uncertainty.
7 Is Stan here?
8 This is for Stan. Dr. Margosches disagreed with
9 the way that we had reworded the LOAEL and NOAEL to define it
10 has either biological or statistical significance.
11 USEPA defines it as both and not either. We define
12 it as either, but historically it ends up driving the
13 decision anyway, and of course, it is always nice where its
14 both.
15 I'm not sure we have actually used only
16 biologically significant in any of these cases, have we, Jim?
17 I do not think we have.
18 Now, I do not know how you want to do this, Dr.
19 Froines, but there were basically six chemicals that got
20 comments on that we wanted to talk about a little bit.
21 The first two are pretty easy. We are going to
22 postpone the discussion of the DEHP and the methyl bromide
23 REL.
24 The reason for the DEHP is we got a public comment
25 that referred to voluminous material already received by
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
149
1 OEHHA under another process, commented primarily on DEHP unit
2 risk factor.
3 However, we do need to go through that material and
4 see if anything is relevant to chronic REL end point.
5 In terms of methyl bromide, we would like to
6 postpone the discussion, because the paper we used is one of
7 the study authors, CMA has requested a letter from one of the
8 study authors, the pathologist, because they had the slides
9 reexamined, and the LOAEL we used might be a NOAEL, so we
10 want to have some discussion of that with the Panel informed,
11 and we need to send you the comment in our response to it
12 before we talk about it.
13 DR. GLANTZ: I heard that my name was taken in vain
14 during my kidney function test.
15 Is there anything that I needed to do, other than
16 you said that methyl bromide, we will bring up next time?
17 Oh, okay.
18 DR. MARTY: Elizabeth Margosches, of USEPA,
19 disagrees with having either biological or statistical
20 significance in determining a LOAEL and a NOAEL, so that was
21 a wording that you had us insert into the document.
22 DR. GLANTZ: Oh, well. She's wrong.
23 CHAIRMAN FROINES: Next slide.
24 DR. MARTY: Okay. We also have hydrogen sulfide
25 where we modify the uncertainty factors that were originally
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
150
1 proposed.
2 Maybe we should wait on these until the Panel
3 Members go around and talk about their chemicals.
4 DR. GLANTZ: I think it is good to go through
5 these.
6 DR. MARTY: Okay. We will go through them then.
7 All right. Methyl ethyl ketone, we changed the
8 basis of the originally proposed REL.
9 We changed the study -- actually, nickel we created
10 two chronic RELs, one for nickel oxide, one for nickel
11 sulfate and other nickel compounds, and then for propylene
12 glycol methyl ether, the industries submitted a chronic study
13 which replaces the subchronic study we had used as the basis
14 of REL.
15 CHAIRMAN FROINES: We do not have that one on our
16 list.
17 According to my list, unless there is a typo, he
18 has only ethylene compounds. There could have been a typo
19 when we did it.
20 DR. MARTY: There could have been a typo when I
21 gave you that original table.
22 DR. ATKINSON: Propylene glycol ethers.
23 DR. MARTY: It is in the document, but it didn't
24 get assigned.
25 That is probably my fault, because I sent you the
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
151
1 table that you could use to assign chemicals to people. I
2 may have left it out.
3 CHAIRMAN FROINES: All I can tell you is what I
4 have here.
5 DR. MARTY: Okay.
6 Hydrogen sulfide, we received comments in the first
7 round of public comment, way back in '97, from Geyser's
8 Geothermal, Lake County AQMD, Pacific Gas and Electric,
9 Unocal Geothermal and the Western States Petroleum
10 Association.
11 Though we did not receive comments on the second
12 round, probably because we changed the number basically for
13 hydrogen sulfide, the concerns that were expressed were that
14 there is already an ambient air quality standard, and that
15 was expressed by several of the commenters.
16 However, that is for one-hour exposure. It is not
17 a chronic number. It is based primarily on odor and the
18 pathophysiologic responses to order.
19 So, we didn't feel that was a reasonable argument
20 to not have a chronic reference exposure level. Then the
21 other concerns primarily related to the feeling of the
22 uncertainty factors were too large.
23 The initial number that we proposed was an USEPA,
24 RFC. We agreed in certain cases with the commenters,
25 revisited that number and have reduced the uncertainty
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
152
1 factors applied to the original study.
2 So, initially the USEPA RfC was the proposed
3 chronic REL. That is .9 micrograms per cubic meter, based on
4 inflammatory changes in the nasal mucosa of mice, and the
5 USEPA uses an uncertainty factor of 10 for subchronic to
6 chronic extrapolation, yet the narrative that accompanies the
7 IRIS documentation indicated that that uncertainty factor
8 should have been three.
9 We agreed with the narrative, and in fact,
10 preferred to use three for a three-month study in mice, which
11 is just under 12 percent of the lifetime.
12 In addition, USEPA uses a modifying factor of three
13 due to database deficiencies in their, the text that went
14 along with the IRIS document said it was in particular for
15 lack of reproductive and developmental studies.
16 Yet there are actually several developmental
17 studies that exist, some of them were published after the EPA
18 generated their numbers.
19 So, they were not available to them. So, we did
20 not think that that modifying factor of three was
21 appropriate.
22 So, essentially, next slide, Jim.
23 The total USEPA uncertainty factor that they had
24 applied was 1,000 to get them to a RFC of nine-tenth
25 micrograms per cubic meter. The total OEHHA uncertainty
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
153
1 factor that we are applying to the same study is 100, and
2 therefore, our reference exposure level is now 9 micrograms
3 per cubic meter, or for those of you that think in parts per
4 billion, that is 7 parts per billion.
5 DR. WITSCHI: I was wondering about this 9
6 micrograms per cubic meter.
7 That was pretty close to the older thresholds,
8 which is 11. As a matter of fact, they are probably the
9 same.
10 So, I notice this is a serious question. I mean,
11 would you want, expect people to put up with this smelly
12 stuff?
13 DR. MARTY: The current ambient air quality which
14 we adopted for one-hour REL is 42 micrograms per cubic meter,
15 and it is based on odor.
16 DR. WITSCHI: Okay. Well, having this around,
17 being forced to smell it, I would consider this a more health
18 effect because it really affects your well-being.
19 DR. KENNEDY: Hyperplasia.
20 DR. WITSCHI: No, I am serious.
21 We do not pay attention to these kinds of things,
22 but that is something that is unpleasant to say the least.
23 DR. MARTY: Well, the International Program on
24 Chemical Safety suggests not to exceed 7 micrograms per meter
25 to avoid complaints of odor, or production of odor nuisance,
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
154
1 just fairly close to that number.
2 I think hydrogen sulfide is one of those chemicals
3 that has developmentally broad odor, individual odor
4 perception threshold.
5 DR. KENNEDY: Species uncertainty factor.
6 DR. WITSCHI: Yeah, but again, shouldn't you
7 protect the most sensitive species?
8 The question is really to consider something that
9 stinks as acceptable by setting standards, which allow us
10 still to discover the stench.
11 DR. MARTY: Well, this one is actually based on
12 histopathology of the nasal mucous rather than odor.
13 It still may be that there are some people who will
14 smell at 9 micrograms per cubic meter. I am not really sure.
15 DR. WITSCHI: As I said, you go by the nasal mucosa
16 of the mouse, and then you hear from the people who complain
17 about the odor.
18 I don't think that is right.
19 DR. MARTY: Would you suggest adding an additional
20 uncertainty factor for the potential odor?
21 DR. WITSCHI: Yes, I would really recommend the
22 level set so that it is not smellable.
23 I know that is not a serious health effect. But I
24 think that is really something we should be considerate of
25 the people.
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
155
1 DR. MARTY: Okay. I think we can look again at the
2 odor threshold data.
3 We have that information and see what a reasonable
4 concentration would be in items of avoiding odor perception
5 and adjust that.
6 CHAIRMAN FROINES: Is there a problem?
7 MR. ALEXEEFF: This is George Alexeeff.
8 What we are looking in terms of the odor threshold,
9 there is a little bit of a complication in terms of trying to
10 resolve, one could put uncertainty factor in and that would
11 be one solution.
12 There is some documentation that, WHO's air quality
13 guidelines for odor perception, hydrogen sulfide is 7
14 micrograms per cubic meters. Just keep it below that to
15 prevent odor complaints, and as I just looked it up. Then I
16 also looked at the study that was contracted out as part of
17 our health analysis for the Air Board on ambient air quality
18 standard, and basically when you get down to about that 7
19 micrograms per cubic meter, you have somewhere, I think, just
20 under five percent of the population being able to detect the
21 odor.
22 There is a large distributional response in terms
23 of the odor detection, and so, about that level that we are
24 talking about, about five percent of the people are able to
25 detect it, so then it becomes a question how far down, the
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
156
1 lowest that we have in terms of evaluating is a two percent
2 value, which would be --
3 DR. MARTY: It's .5 parts per billion is detected
4 by 2 percent of the population.
5 MR. ALEXEEFF: We should be under a microgram per
6 cubic meter, which gets us actually to the RFC, would be
7 about 2 percent.
8 CHAIRMAN FROINES: I would like to propose that we
9 take a 10 minute break right now, and you folks talk to Peter
10 to resolve --
11 DR. WITSCHI: That is a larger issue.
12 CHAIRMAN FROINES: I have a problem.
13 We have a problem because we have not yet got to
14 discussing all these chemicals with the exception of the few
15 that we did with Paul Blanc, and we have people from DPR
16 waiting to finish this morning's activity, and so they are
17 trapped.
18 We have not started this, and we have also to do
19 the entire exposure workshop part tomorrow. So, we have an
20 obvious time problem.
21 So, in a sense we still have three major areas that
22 we have not completed. So, I would like to talk to Bill and
23 whoever is here from DPR to talk about how we are going to
24 schedule things.
25 So, if we can take a 10 minute break, I think that
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
157
1 would be good, and then we can see where we are going to go
2 with this and if Peter wants to talk to the nose people.
3 (Thereupon a brief recess was taken.)
4 CHAIRMAN FROINES: Okay. We have a quorum, I
5 believe.
6 Are you okay?
7 DR. MARTY: I thought we could go through the
8 chemicals individually so we cannot worry about the rest of
9 my slides until the chemical comes up.
10 CHAIRMAN FROINES: Okay. We did make a mistake.
11 Propylene glycol was the chemical, and we assigned
12 it to Peter Kennedy, but when the list was typed up,
13 apparently there was a mistake made, and it was omitted.
14 So, there was an error. So, let's start with --
15 let me tell the Panel what we decided we are going to go as
16 far as we can, and we will stop between 4:30 or 5:00.
17 Gary has to leave at 4:30, and then we won't finish
18 all these chemicals today, so we will then put the rest of
19 the chemicals over until the next meeting, tomorrow. So
20 tomorrow will be exposure monitoring of DPR and
21 prioritization.
22 So, we will finish this section at the next
23 meeting, probably.
24 So, Craig, why don't you give us --
25 DR. BYUS: I do not have too many things to say
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
158
1 here.
2 I had to borrow Dr. Blanc's book, because I forgot
3 my book. So, I wrote some notes in his book.
4 It occurred to me under diethylhexylphthalate,
5 which was my first one, how do you deal with sort of
6 hypersensitivity phenomenon, as we were talking about one
7 exposure and looking for response that comes up later, and
8 this would kind of be an example of that.
9 Do you -- it is conceivable you might not see an
10 effect and then challenge an animal again and you might see a
11 hyper sensitivity type reaction.
12 Do you address that at all?
13 DR. MARTY: If we have animal data describing the
14 phenomenon, we would definitely look at it.
15 DR. BYUS: Most of them are probably not really
16 tested in that sort of paradigm of a small exposure, say
17 followed later by another challenge.
18 I mean, you have to set that up as a
19 hypersensitivity sort of assay. I don't think you may or may
20 not see it.
21 DR. SALMON: It can be done and has been done with
22 some chemicals which are known to have epidemiological
23 effects, but it is not something which we commonly see on
24 these kinds of agents.
25 That is, of course, if you are talking about
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
159
1 hypersensitivity as narrowly defined as a epidemiological
2 effect, but there are, of course, people out there that are
3 not confined in the broader sense.
4 DR. BYUS: No, I do not mean that whole
5 environmental chemical phenomenon.
6 I'm talking about classic hypersensitivity.
7 DR. SALMON: Specifically within the area of review
8 immunotoxicology, there are screens for hypersensitivity
9 effects.
10 In fact, they are used for screening chemicals in
11 some contexts.
12 DR. BYUS: But you are not really dealing with that
13 effect here in these calculations?
14 DR. SALMON: We have not dealt with this in this
15 particular case, no.
16 DR. MARTY: We did for the acute reference exposure
17 levels, for some of them.
18 Nickel is the one, and I know there are a lot of
19 studies on that for nickel.
20 DR. SALMON: There are also cases where there is
21 human exposure evidence which depends on that phenomenon.
22 DR. BYUS: I thought of another weird example.
23 Chloramphenicol, even few exposures you get a delayed
24 aplastic anemia that shows up later.
25 That is probably a hypersensitivity mediated effect
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
160
1 on the marrow somehow.
2 They do not quite know the mechanism of it, but it
3 is a very unusual. It is a case where you have exposure to a
4 drug for a short time, and you see an effect later.
5 Even after the drug is withdrawn, it is
6 irreversible.
7 DR. SALMON: I am afraid there has been a bit of --
8 truth of the matter is I do not think that we know about such
9 an effect unless it has been observed in human subjects.
10 DR. BYUS: Okay. I think, that is the probably
11 correct.
12 Okay. One quick question. What is a slime assay?
13 Just to show you that I did read this.
14 DR. MARTY: Is somebody from DPR still here?
15 I think slime is a mold. So, slime assay is a real
16 word.
17 It is not the stuff your kids play with.
18 DR. SALMON: It is a common problem in cooling
19 systems and humidifiers and things of that sort.
20 DR. BYUS: Okay. On page 198, you refer about
21 phenol, this original, one of these old studies by Boutwell,
22 which actually the two are promotion studies, that is why it
23 caught my eye.
24 The dose here, you said, chronic study in mice
25 involving skin painting at 1.2 mg., or 2.5 mgs., for a 52
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
161
1 week period.
2 Now, there is something. Usually you apply so much
3 twice a week, or is some dose missing there? Something is
4 missing.
5 DR. MARTY: There is something missing, I agree.
6 The X number of times per week.
7 DR. BYUS: That is all there.
8 DR. MARTY: I actually have something to bring up
9 on phenol, and that is, when I was looking at this recently
10 to be, could be consistent, we should have used a sub chronic
11 uncertainty factor of three there rather than one.
12 If we do that, then the total cumulative
13 uncertainty factor will be 100, and the REL will be .05 PPM,
14 and we may need to think about whether we really need to do
15 that or not.
16 DR. BYUS: Probably that would be good.
17 There is a lot of smell about phenol, too, just
18 from personal experience with the compound.
19 DR. MARTY: Not as bad as --
20 DR. BYUS: No, not as bad, but it is pretty bad.
21 DR. GLANTZ: So, saying they should use a factor
22 and add the factor of three in?
23 DR. BYUS: Probably.
24 But again, I am far from an expert on this. I read
25 it, but without reading all the original stuff. This is
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
162
1 tough for me, this stuff here, is what I am telling you.
2 DR. MARTY: It is tough for us, too.
3 DR. BYUS: I know.
4 DR. GLANTZ: I think, just to be fair, so, are you
5 guys, you either need to put the three in or not put the
6 three in, I mean, what are you going to do?
7 DR. MARTY: What I wanted to do is figure out from
8 the staff person who originally did this, who is not with us
9 any longer -- he is alive, but he does not work for us any
10 more, what the reason was for not using three.
11 So, if there was a really good reason, maybe we
12 should. But if there wasn't, and it was an oversight or some
13 other thing happened, then maybe we should.
14 So, if I could buy a little bit of time on that
15 one.
16 DR. BYUS: Okay.
17 Then I actually did read propylene, which was on my
18 list, and it appears that somebody else did propylene, is
19 that what you were just telling me earlier?
20 DR. GLANTZ: Propylene glycol methyl ether.
21 DR. BYUS: So, all of this metaplasia, hyperplasia
22 discussion we just had applies to propylene as well.
23 Actually, it was also this weird difference between
24 the animals as well, which I thought was a little unusual.
25 Other than that, I would probably agree with your analysis.
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
163
1 Propylene oxide, my only question was, an oil
2 demulsifier, what is that exactly?
3 What does that mean?
4 I am not looking for trivia here?
5 DR. SALMON: I think it is a chemical that actually
6 breaks down emulsion.
7 DR. BYUS: We are whipping along.
8 Propylene oxide, on 219, and I had no other
9 questions about that.
10 Now, styrene was the most complicated for me to
11 read and the most complicated for me to understand. Really
12 what I don't understand about it, it seems like it is quite a
13 nice analysis, but the neurotoxicity in humans, you really
14 don't ever describe exactly.
15 I read it through three times trying to find out
16 exactly what it is, critical effects, neurotoxicity in
17 humans.
18 I have a couple more things on that, but that was
19 the main, if you go down to say, 229, its critical effects,
20 central nervous system, that is really not a good description
21 of the toxicity.
22 Apparently you are using this test where they,
23 something, they used eight neuropsychological tests, but you
24 don't describe it anywhere, and you really don't describe the
25 toxicity in very much detail.
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
164
1 Am I wrong?
2 DR. MARTY: Well, I do have it in, but maybe its
3 not described well enough.
4 So, we can go into that.
5 DR. BYUS: I mean, if you just read from 229 on, I
6 keep looking for where is the, what is the neurotoxicity?
7 DR. MARTY: There is more on page 225.
8 DR. BYUS: Which paragraph?
9 MR. LEWIS: The last paragraph.
10 DR. MARTY: It's the --
11 DR. BYUS: Right.
12 A battery of neuropsychological tests designed to
13 measure CNS function.
14 MR. LEWIS vocabulary tests and motor function.
15 DR. BYUS: Okay. It seems like you ought to just
16 provide a little bit more better description of what you call
17 the central nervous system.
18 DR. MARTY: Okay. We will describe the tests
19 better than what was used.
20 DR. BYUS: You need to describe what it is exactly,
21 in a sense, I think, because I could not, I had a difficult
22 time finding it.
23 The other question I had about the styrene was --
24 oh, on page 225, you said worker's styrene exposure was
25 assessed by the next morning urinary MAPGA.
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
165
1 I actually have a question about that that actually
2 shows up virtually on page 223. I am going backwards here.
3 On page 223, it says occupational studies are the
4 basis for quantifying relationships between chronic styrene
5 exposure and health effects, end-of-shift or next-morning
6 MA+PGA have been used.
7 They are the metabolites for this. Just explain to
8 me that rationale. You are saying that these metabolites
9 have a longer half-life.
10 Explain to me what that means. I just never heard
11 that term. Maybe it is an occupational exposure term.
12 You say it several times, end-of-shift or next
13 morning. In other words, you wait till the next day to
14 measure these metabolites, then you say that is a better
15 indication of exposure of the previous day.
16 DR. MARTY: Right, because of the fat solubility of
17 styrene, so it goes into the fat and then redistributes it
18 when they come home from work.
19 DR. BYUS: Okay.
20 DR. SALMON: There has been quite a lot of work
21 actually showing correlation between the various measures of
22 urine or metabolites and exposure assessed by personal
23 monitoring and that kind of thing in the workplace.
24 DR. BYUS: I teach pharmacology, and it is called
25 drug redistribution, and there is not many good examples of
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
166
1 it.
2 I was not aware of this one, and I will have to use
3 this one, but it is a good example.
4 The last thing -- oh, it was back on 225, workers
5 with metabolites, in the last paragraph, concentrations up to
6 150 per millimoles per mole, millimoles per mole is a
7 concentration, what do you mean, is millimoles a creatinine
8 or what is the unit there?
9 I don't quite --
10 DR. MARTY: In table 1, millimoles per mole
11 creatinine.
12 DR. BYUS: I don't know if I would use the word
13 concentration.
14 Creatinine is the function. It is normalizing for
15 urine output for kidney functions. So, whatever that --
16 DR. MARTY: We can fix that.
17 DR. BYUS: That is it.
18 Anyone else?
19 DR. MARTY: Okay.
20 CHAIRMAN FROINES: What would be the calculated REL
21 if you used animal data?
22 DR. BYUS: For styrene?
23 DR. MARTY: Well, I don't have that in front of me,
24 because we did not use animal data.
25 So, I would have to go back and look at probably
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
167
1 the NTP study would be the best bet in terms of chronic study
2 and figure that out.
3 CHAIRMAN FROINES: Okay. We will not worry about
4 it.
5 DR. BYUS: That is why, that is the main reason I
6 think why you should explain this stuff, neurotoxicity tests
7 that were actually performed as the basis for the REL
8 calculation.
9 DR. MARTY: The NTP study defines a LOAEL but not a
10 NOAEL.
11 So, you probably automatically have a thousand fold
12 that is already factored, because you have the inter species
13 intra species and LOAEL to NOAEL, so you would end up at 62
14 parts per billion as opposed to 300 parts per billion.
15 DR. BYUS: What is the subchronic then, 13 weeks?
16 DR. MARTY: Oh, I'm sorry, this is their range
17 finding, 13 week study.
18 The next by alphabet is Dr. Friedman.
19 CHAIRMAN FROINES: No, no, I'm not finished.
20 I'm still waiting. I thought that you were going
21 to say something more about this.
22 MR. LEWIS: It would probably be with the
23 calculations just out of our heads, would probably be 10 to
24 20 times lower than the human calculations.
25 CHAIRMAN FROINES: And under this theory of the
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
168
1 most sensitive model, why would you then not pursue that?
2 DR. SALMON: I think the animal number would
3 include a large amount of uncertainty because of additional
4 extrapolations that would be necessary.
5 So, the human number is a number which we have
6 greater confidence.
7 CHAIRMAN FROINES: Well, maybe, maybe not.
8 Because exposure characterization is much worse
9 when you do human studies. I see that all the way through
10 that argument, but that is not necessarily correct given the
11 weakness of exposure assessment that occurs always in human
12 studies.
13 So, it is not apparent to me that that is correct.
14 DR. MARTY: Well, in this case though, you have a
15 human study that is just about chronic.
16 In fact, it is debatable whether you call that
17 chronic or not, and you have a NOAEL that has been defined.
18 In the case of the animals, its sub chronic LOAEL, so you
19 just end up with more uncertainty, because you don't even
20 know where you are on the dose response curve with respect to
21 the NOAEL, you don't have the interspecies extrapolation
22 problem if you use humans.
23 CHAIRMAN FROINES: One thing that is true about
24 people who work with styrene, they get it all over their
25 hands, arms, faces and bodies and they have enormous dermal
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
169
1 absorption.
2 So, your estimate of dose is clearly flawed when
3 you take that into consideration, people don't work with
4 styrene and keep it off their bodies, and consequently
5 whenever you are working with one of these solvents, where
6 you are having a high uptake and working, kind of working
7 conditions where people are going to get it on their bodies
8 and you estimate exposures based on that, you may say that
9 the animal data is much worse, but I would argue that you
10 have much of a real guess about what the exposures are under
11 those circumstances, and the problem with exposure assessment
12 with high dermal absorption is that it is obvious.
13 DR. MARTY: Well, you know, we do recognize that
14 one of the major problems with epidemiology is the exposure
15 assessment, and it is definitely an uncertainty, but I am not
16 sure there is a whole lot that we can do about it, unless you
17 have -- there is reconstruction of the exposure that included
18 dermal, if you made an effort to do that.
19 How you do that with this particular study, if the
20 doses were actually higher than predicted by the air
21 concentration, that would make the difference between the
22 animal REL and the human REL even bigger.
23 CHAIRMAN FROINES: That is right, exactly.
24 DR. BYUS: They were using in the one study, they
25 used your urinary metabolite data as a sign of exposure, so
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
170
1 theoretically that would take that into consideration, the
2 dermal exposure.
3 DR. MARTY: But they went backwards to get an air
4 concentration.
5 CHAIRMAN FROINES: Hence the problem.
6 DR. BYUS: Hence the problem.
7 CHAIRMAN FROINES: See the trouble with these
8 little three page, four page documents is you don't explore
9 anything in depth.
10 Some of these issues require some measure of depth.
11 If I were you, I would put in animal value and put in a
12 couple of paragraphs, and then actually discuss this, the
13 uncertainties and what the relative approaches would be.
14 DR. MARTY: For each one where we used the human
15 study, if there was an available animal study, do you want us
16 to do that?
17 CHAIRMAN FROINES: I think styrene is an extremely
18 important chemical.
19 I mean people are actually exposed to styrene. We
20 read in the newspaper all the time about styrene spills out
21 of tank trucks and tankers.
22 This is, we can leave it for now, and come back to
23 it later, but I think the issues are, I think we have to
24 avoid major reactions to human studies, because they are
25 human studies, where you have some vast uncertainty in the
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
171
1 exposure, whereas in the animal study, you actually can
2 control exposure.
3 DR. MARTY: It is vastly different than in the
4 species.
5 CHAIRMAN FROINES: I don't know.
6 That is what we are trying to spend time finding
7 out, and so -- but I think to simply ignore one for the other
8 isn't necessarily appropriate either.
9 I have not spent time looking at the styrene one.
10 I will look at it, and I will tell, I will follow-up and talk
11 about it some more.
12 Let's leave it for now. So that the next person is
13 Gary.
14 DR. FRIEDMAN: Before I start on the individual
15 chemicals, I just wanted to say that I really appreciate the
16 productive meeting that I had with Andy Salmon and David
17 Lewis and Jim Collins, where they came over and we discussed
18 my concerns about the introductory portion of this document,
19 and it was very helpful to me, and I hope it was helpful to
20 you, too.
21 Regarding benzene, I had only one concern about
22 this write-up. I had a question about, if the chronic
23 exposure requires at least eight years, and with the mean
24 here was 7.4 years, why this was called a chronic exposure,
25 and it was explained to me that 32 percent of the workers
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
172
1 were exposed for over 10 years, and since 7.4 was close to
2 the requirement of 8, they made a judgment call to call this
3 a chronic study, and I think that is fine, but I think you
4 probably should add this to the write-up.
5 Just put that explanation in your write-up the same
6 as you explained to me.
7 DR. MARTY: Okay.
8 DR. FRIEDMAN: With regard to ethylene glycol, I
9 had -- my concerns were based on your -- applies to the
10 comments that came in, on page 12, of the comments.
11 This was by the Chemical Manufacturers Association.
12 There was some -- their comment, one, talked about your REL
13 of 400 micrograms per cubic meter, and they said based on the
14 numbers that you gave it really should have been 508
15 micrograms per cubic meter, and this was based on some
16 rounding that you did, that you rounded .167 parts per
17 million.
18 You first rounded that to 0.2. That would come up
19 to the number closer to 500, and you went ahead and agreed
20 with that and did what they said.
21 DR. COLLINS: That was my error.
22 I just didn't carry the number into the table. We
23 will certainly change that to the final number if there is no
24 other concerns.
25 The final number that we will use will be 500.
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
173
1 DR. FRIEDMAN: My question is, why not use the
2 original .167, which if you do that and go through these
3 multiplying by uncertainty factors, you end up with, what I
4 came up with was 423, which is closer to your 400, so why not
5 stick with that?
6 Why be victimized, so to speak, by this initial
7 rounding to .2? Why not stick with the original more
8 accurate number?
9 DR. MARTY: Well, I think that is a good point.
10 Isn't the general rule you don't round until the
11 end?
12 So, it should be 400 not 500.
13 DR. FRIEDMAN: Right. Okay.
14 Then on page 13 of the comments, again, responding
15 to Chemical Manufacturers Association, there was some concern
16 about whether you use the highest mean value or the highest
17 high value, and they, I guess, proposing that they use the
18 highest high value, and you said, that the mean is more
19 appropriate, but you didn't explain why, and I think it would
20 be helpful if you could explain why you prefer to use the
21 mean.
22 In fact, if you don't mind telling me that now, I
23 would appreciate it.
24 DR. MARTY: Okay. Well, the estimates of
25 concentration, we felt it was more appropriate to use a mean
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
174
1 for that group of people who were estimated to be exposed
2 somewhere between 20 and 66.8 as their concentration, and the
3 mean better represents the population exposure than the high
4 end value for the low end value.
5 DR. COLLINS: Ultimately it is going to be compared
6 as the average value for the year, and we know during the
7 year everything is going to go up and down, but there will be
8 an average over the people being exposed.
9 DR. FRIEDMAN: That would be worth stating in the
10 response to the comments or somewhere, because you say we
11 like the mean better and do not explain why.
12 DR. MARTY: We can add that.
13 DR. FRIEDMAN: That is all I had on ethylene
14 glycol.
15 CHAIRMAN FROINES: I have a question, the basis of
16 this REL is human volunteer prisoners, and it is respiratory
17 irritation, and this is a chronic study?
18 DR. MARTY: It is sub chronic.
19 DR. COLLINS: It was 30 days, and we used it as a
20 sub factor of 10.
21 CHAIRMAN FROINES: These are chronic RELs, and you
22 are using that for a chronic REL?
23 You really think this is an example of a chronic
24 condition?
25 DR. MARTY: Well, I am not sure that you would see
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
175
1 increased respiratory irritation.
2 I do not think it would be very different than 30
3 days or 30 months. I do not know that for a fact, but you
4 know, it may not fit the paradigm particularly well, but we
5 did use the sub chronic uncertainty factor of 10 to try to
6 account for the fact that it was a sub chronic study and not
7 a chronic study.
8 CHAIRMAN FROINES: It rather looks like acute
9 toxicity to me.
10 DR. KENNEDY: The issue seems to be not the number
11 but the origin of reference, if you will.
12 A scratchy, running nose is a chronic response.
13 DR. MARTY: Well, it may follow under one of those
14 like formaldehydes where it is repeated acute exposures in
15 the work place and that you see the symptoms.
16 They are reversible, but in the case of
17 formaldehyde, they do not reverse immediately upon cessation
18 of exposure.
19 It could be several weeks before the nasal symptoms
20 go away. So, it does fall into that category, deep.
21 Is it appropriate to develop a chronic REL or not
22 for something that is an irritant?
23 MR. LEWIS: One of the other problems is, we really
24 do not have any long-term animal studies for inhalation
25 either.
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
176
1 CHAIRMAN FROINES: But that is not the point.
2 DR. KENNEDY: If you don't, you don't.
3 Maybe that is the answer.
4 CHAIRMAN FROINES: I have to say I have a lot of
5 problems with a study like this, where you are basically
6 producing what seems to be acute toxicity.
7 I think of chronic effects as chronic effects, not
8 necessarily the fact that you can see the effects over a
9 period of time.
10 I mean, I think you have to see them as a chronic
11 effect. Respiratory irritation is not necessarily a chronic
12 effect.
13 It means that if you are exposed to it every day,
14 you can have effects every day.
15 That is an acute effect that occurs repeatedly.
16 That is not chronic effect.
17 DR. MARTY: There is some information with
18 respiratory irritants that duration of exposure does impact
19 the level of response.
20 So, you should be a little careful in interpreting
21 it that way.
22 CHAIRMAN FROINES: I wrote the standard for cotton
23 dust.
24 Believe me, I know. This is, when you look at this
25 little study, it does not make you think of business or any
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
177
1 hematological-based responses.
2 DR. FRIEDMAN: John, we are not talking about
3 chronic effects, but we are talking about effects of chronic
4 exposures.
5 Isn't that really what you are trying to talk
6 about, effects of chronic exposure rather than chronic
7 diseases that results from exposures?
8 DR. MARTY: Yes.
9 I think that is what we are trying to do, talk
10 about impacts of being exposed chronically.
11 CHAIRMAN FROINES: Yes. But you are selecting an
12 end point.
13 DR. FRIEDMAN: But if it takes 30 days of exposure
14 to produce this irritation of the respiratory --
15 CHAIRMAN FROINES: Respiratory irritation was noted
16 after 15 minutes.
17 DR. FRIEDMAN: Well, that is an acute affect.
18 CHAIRMAN FROINES: That is right.
19 They may have given the stuff up to 20 to 30 days
20 without effect, but respiratory irritation occurred in 15
21 minutes at 75 parts per million, and it became quickly
22 intolerable with 123 parts per million.
23 As I read this, it sounds like an acute affect.
24 The way this is written, it is an acute affect that we are
25 talking about.
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
178
1 Am I completely crazy?
2 DR. BYUS: No.
3 We just did this with the methyl parathion. There
4 were so many studies, chronic, sub chronic, acute and
5 multiple, and they had the whole document with all the
6 studies, and you could really look through them all and
7 figure out what the appropriate numbers would be, which you
8 are exactly right, with the sort, types with this one little
9 study, it is very difficult to make the judgment.
10 DR. SALMON: There are no studies which indicate
11 effects other than the continuing acute effects as a result
12 of chronic exposure.
13 So, we have no information about to suggest that
14 there are what you would call chronic effects which result in
15 chronic exposure merely in continuing acute effect.
16 CHAIRMAN FROINES: Then we should set up an acute
17 REL and not set up a chronic REL.
18 DR. MARTY: The only other basis for worrying about
19 it is, there are chronic feeding studies in animals, and you
20 can do a -- but that gets into a whole other Pandora's box.
21 If you do that, you come up to about the same
22 inhalation realm, and they have end points that they measure
23 that are not respiratory irritation but reduced body weight,
24 reduced RBC counts.
25 CHAIRMAN FROINES: When was the last time somebody
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
179
1 saw ethylene glycol at 75 parts per million?
2 Unless somebody has a fire in their car and that
3 stuff gets heated to high temperature, so there is some level
4 of vaporization, I do not know of when anybody ever gets
5 exposed to ethylene glycol.
6 DR. MARTY: Well, it is not on our database.
7 There are emissions of ethylene glycol. In most of
8 the glycol ethers, they are not particularly volatile. They
9 end up in the air because they are being used at high
10 temperatures and pressures, and who knows what happens to
11 them after they get in the air, if they end up aggregating or
12 glomming on to particulates.
13 CHAIRMAN FROINES: Ethylene glycol, the issue of
14 ethylene glycol ethers is, there is a significant dose, they
15 go through the skin like a shot.
16 They have very high dermal absorption.
17 So that the concern that has existed for a long
18 time on glycol ethers, for example, in cleaning solvents, is
19 not because of inhalation, but because of skin contact.
20 So, we should not create a problem where none
21 exists.
22 Ethylene glycol, I think, and I think that most of
23 us have had some contact with ethylene glycol and survived
24 the experience.
25 The question is, when I look at this paragraph, I
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
180
1 see an acute study showing irritation, and I see no evidence
2 whatsoever for chronic effects associated with long term
3 exposure to ethylene glycol.
4 DR. FRIEDMAN: Didn't they use the NOAEL at 20, and
5 that is what they used to calculate the REL.
6 So, there is no effects at 20 parts per million, no
7 long-term effects, and that is the number they used.
8 CHAIRMAN FROINES: But there are no long-term
9 effects.
10 DR. FRIEDMAN: That is what they found.
11 CHAIRMAN FROINES: But it is like choosing a NOAEL
12 for a non end point.
13 You cannot do it.
14 DR. MARTY: Well, we keep coming back to the fact
15 that do you need to have a chronic REL for something as a
16 respiratory irritant, because that is essentially an acute
17 effect that may be repeated over time.
18 CHAIRMAN FROINES: There are different respiratory
19 irritants.
20 My guess is formaldehyde is a very serious issue,
21 and we could put it in a different class than we do ethylene
22 glycol.
23 With this paragraph, as I read this little tiny
24 paragraph, it looks to me like an acute effect.
25 DR. MARTY: We actually say in here that it is an
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
181
1 acute effect.
2 See, although the irritation experienced in the
3 human subject appears to be an acute phenomenon and an
4 accumulative lasting effect, we still applied an uncertainty
5 factor to protect against other systemic effects, which may
6 occur over a long-term exposure.
7 So, in other words, we do not know what happens
8 with long term exposure. Therefore, we are applying this
9 other uncertainty factor.
10 Yes. That mixes apples and oranges then because
11 you are mixing the respiratory end point with whatever else
12 might happen.
13 I'm perfectly happy taking this REL out.
14 CHAIRMAN FROINES: We should be focusing our
15 attention on things that constitute problems and not simply
16 having long lists of chemicals with very low REL that have no
17 significance in a societal context, and this one does not
18 have any societal implications, and if I am wrong, I will
19 stand corrected.
20 But I do not think this one is one that we see
21 causing very many people being chronically ill, and that is a
22 problem.
23 DR. MARTY: We can also look at the emissions
24 database and see how much is in -- It was in the top 40 in
25 terms of pounds per year.
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
182
1 But then again, is the pounds per year out of a
2 whole bunch of facilities or is it pounds per year mostly out
3 of a couple of facilities?
4 In which case is a hot spot in that area? We are
5 going to have to figure it out.
6 CHAIRMAN FROINES: Where do you think all this
7 stuff comes from?
8 DR. MARTY: Well, I think ARB would have to help me
9 out on the types of facilities that are remitting it, but it
10 has been used as a solvent in a lot of different processes.
11 CHAIRMAN FROINES: Well, I don't know.
12 I frankly think that this compound we should have
13 an acute REL for it, and I cannot see any basis for chronic
14 REL based on what I see, unless there is more to this little
15 paper.
16 DR. MARTY: That is it.
17 There is not more, unless you start looking. The
18 problem is really in this case is a lack of data rather than
19 lack of data and looking.
20 DR. FRIEDMAN: There were chronic effects in
21 animals inhaled and produced all of these problems in mice,
22 and so it is not unreasonable to think that if people were
23 exposed chronically there might be a problem.
24 CHAIRMAN FROINES: Well, set a REL based on the
25 animal data.
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
183
1 DR. FRIEDMAN: No.
2 It says, study effects have inhaled ethylene
3 glycol, in the second paragraph of animal.
4 DR. MARTY: On the reproductive developmental
5 study.
6 There was maternal toxicity but no developmental
7 other than delayed ossifotification.
8 Those were pretty high concentrations.
9 CHAIRMAN FROINES: Why don't we move ahead.
10 DR. FRIEDMAN: Okay. The next one I have is,
11 Telone, and I have some questions about that.
12 On page 238, it talks about a study,
13 neurobehavioral tests and some workers that were exposed, as
14 a significant decrease in neurobehavioral performance was
15 observed in the exposed workers, and 6 out of 8 tests, and
16 they were exposed to 88 parts per million, and therefore, you
17 use that as the LOAEL, and maybe I do not understand how you
18 derive a LOAEL, but that sounds like if there was a lower
19 concentration, there would still be problems there.
20 So, there is this one concentration and a fairly
21 significant result. Why did you pick that as the low adverse
22 effect level?
23 MR. LEWIS: Well, because that was the dose level
24 we had. The low level was the first to be observed.
25 The lowest level was not the lowest dose.
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
184
1 DR. FRIEDMAN: If they had all died, would that
2 still be a LOAEL?
3 DR. MARTY: Well, if we had fatality, we would not
4 use that to establish.
5 If we just had data, we wouldn't use it to develop
6 our reference exposure level.
7 DR. FRIEDMAN: I would like to note that this is a
8 RfC, so it is something that we did take to USEPA, rightly or
9 wrongly.
10 Well, then related to that in the third paragraph
11 on that page, it talked about solvent workers were exposed to
12 42.8 parts per million and no significant difference from
13 controls were noted.
14 Why didn't you use that study in calculating,
15 let's say, in NOAEL? That was a NOAEL, I guess, study, why
16 didn't you use that rather than the one that we just talked
17 about?
18 DR. MARTY: I would have to go back and look why we
19 did not use it.
20 The only statement that we have in here is that the
21 study did not account for confounders.
22 DR. FRIEDMAN: Well, the college level study is
23 only three days.
24 MS. MARTY: And the other thing is, this is a USEPA
25 RFC, which we just proposed adopting without modifying it,
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
185
1 and so in those cases, we really did not do a lot of leg work
2 looking at other studies.
3 DR. FRIEDMAN: You know, I do not know since there
4 was no effect, I'm not sure how important smoking and alcohol
5 consumption would have been as confounders there.
6 DR. MARTY: That is a good point.
7 DR. FRIEDMAN: Well, I think it would be nice if
8 you decided, it would be good to be explicit as to why you
9 picked the previous study rather than that to use, and then
10 in the calculations you did the derivation of the RFC or the
11 USEPA did it, and it looked to me that there might be an
12 arithmetic mistake, other than the LOAEL that was used as 88
13 parts per million and the cumulative uncertainty factor was
14 300, when I divided 300 into 88, I got .29 rather than 0.1.
15 DR. COLLINS: You mean divide 31.4, which was the
16 average down exposure?
17 The average occupational exposure was 31.4 PPM,
18 converting intermittent to continuous, so we divide 31.4
19 times 300 to get 1.
20 DR. FRIEDMAN: So, you use that rather than the
21 parts per million?
22 DR. MARTY: There was a time adjustment from the
23 discontinuous occupational exposure to what would be
24 equivalent to a continuous exposure by multiplying.
25 DR. FRIEDMAN: So, you use that in addition to the
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
186
1 uncertainty factor, okay.
2 MS. MARTY: Right.
3 DR. FRIEDMAN: Okay. Those are my questions on
4 that.
5 Then trichloroethylene.
6 CHAIRMAN FROINES: May I step in and ask a
7 question?
8 I frankly think that Telone is one of the most
9 important solvents in the State of California, and I do not
10 know what the numbers are in terms of use, but it is fairly a
11 big effect in many respects.
12 I frankly think that you all should state a REL for
13 this compound and not rely on EPA, and do a thorough
14 elevation of the literature. This is a high use compound in
15 this State.
16 Telone is everything. There have been multiple
17 Prop 65 suits around Telone and so forth. I think that this
18 is such an important compound, I just think it is better if
19 we, if you had done a thorough evaluation and developed an
20 REL as opposed to using the EPA number, because clearly, Gary
21 is right.
22 The amount of information in here to make a
23 decision on this really important compound is very limited.
24 I do not know why you don't develop an REL for this compound.
25 Is this based on a thorough analysis of all the
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
187
1 literature?
2 DR. MARTY: Well, it was based on a policy decision
3 to adopt USEPA RFCs where they were available and where we
4 did not disagree very much.
5 CHAIRMAN FROINES: This Panel has also been very
6 clear on that.
7 This Panel says that we do not want to use USEPA's
8 standards unless we think they are appropriate and adequate.
9 DR. MARTY: Not your policy but the policy of Cal
10 EPA and in part in response to a Governor's Executive Order,
11 the previous Governor, to harmonize whereever possible with
12 USEPA.
13 That is the origin of having us propose to you
14 USEPA RFCs.
15 DR. GLANTZ: Well, there have been several cases
16 going through this document and that people seem to accept
17 that, but clearly this is not one of them.
18 So, what I think you ought to do is, when this
19 comes back in the next draft is do what John has suggested,
20 for this one compound.
21 I don't think they are suggesting they should go
22 back to the other ones that people seemed okay with, but for
23 this one, I think --
24 DR. MARTY: That is fine.
25 CHAIRMAN FROINES: I just think that Telone is so
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
188
1 important, such an important widespread exposure, that when
2 we get one like that, that really may impact people, we ought
3 to really feel confident that we have best evaluation.
4 That is a compliment to you folks, because what I
5 am really saying is that we think that most of the time you
6 do a better job than EPA. So, we have more confidence if you
7 have done it than if they have done it.
8 So, it is a statement that is supportive rather
9 than critical. I just think that this is -- it seems to me
10 that Gary is right, that there are some uncertainties in the
11 way the numbers actually ended up getting selected.
12 DR. MARTY: Okay.
13 DR. FRIEDMAN: Next is trichloroethylene, and on
14 page 244, apparently the top study that you described,
15 Vandervort and Polnkoff was the one that you used for
16 calculating the REL, and just reading the last few lines of
17 that first paragraph, says, urine samples from the 19 exposed
18 and 9 unexposed workers were collected before and after the
19 work shift and examined for the TCE metabolites, etcetera.
20 TRI levels ranged from 4 to 260 milligrams per
21 liter and TCA levels from 4 to 197. Results of the urine
22 assays showed a range of metabolites concentration.
23 Therefore, confirmed that the workers were exposed to a
24 variety of concentrations in their evnvironments.
25 It is not clear from me reading that that the
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
189
1 controls had less exposure then the so-called exposed ones.
2 I mean, all you talk about is the range and all the
3 subjects, and it was not clear to me that there was a
4 difference between exposed and unexposed.
5 So, I think something more needs to be said about
6 that.
7 I noticed later in this you go into great detail
8 about histologic changes in the brain of animals, which was
9 not used in determinations, so, I thought there was sort of
10 an imbalance there of how much attention you paid to
11 something that was relatively unimportant, compared to this
12 study which was the one on which your calculations were
13 based.
14 DR. MARTY: Okay. We will expand that discussion
15 of the study.
16 DR. FRIEDMAN: I was not clear how the 32 in the
17 derivation, on page 249, I wasn't clear how the 32 parts per
18 million, how that number was picked for the LOAEL.
19 Again, in one of the questions that I wrote down
20 here, I don't remember the details, but why didn't you use
21 the mean, because you had argued that you should use the mean
22 in the ethylene glycol situation.
23 Why didn't you use the mean exposure here?
24 DR. MARTY: I think we did, actually.
25 DR. FRIEDMAN: It says that the averages ranged
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
190
1 from 32 to 78 parts per million, and you used 32, so you used
2 the lowest of the averages. That is in line 5 of page 244.
3 DR. MARTY: Okay. We have to go back and figure
4 out why we did that.
5 MR. LEWIS: The average worker was in that range,
6 and in summary, the worker with the lowest average exposure
7 of that 32 PPM --
8 DR. MARTY: Well, it could be that they chose that
9 number because it was the lowest number associated with an
10 adverse effect.
11 DR. FRIEDMAN: Before you argued that the mean
12 should be used rather than something at the extreme, when you
13 were saying the high should not be used, why would you agree
14 to using the low?
15 DR. MARTY: I don't know.
16 Maybe just because we call it the lowest observed
17 adverse effect levels. If people exposed at 32 still showed
18 effects that is the lowest observed adverse effect level, and
19 it just may be that that's the point that it turns on, but I
20 can check.
21 DR. FRIEDMAN: Okay. I think you may need to list
22 just a little more explanation there.
23 Xylenes, I had a few questions -- let's see.
24 DR. ATKINSON: That is actually said on page 249,
25 isn't it?
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
191
1 It's on the first four paragraphs of why you chose
2 the 32.
3 DR. MARTY: Symptoms were not reported severally
4 for the various time weighted averages, therefore, the lowest
5 time weighted average was chosen as the LOAEL.
6 DR. FRIEDMAN: Okay. So, you do explain it.
7 Xylenes, page 253, you talk, the first paragraph
8 under effects of human exposure, you say in the middle of the
9 paragraph, one study examining chronic effects in humans from
10 inhalation of predominantly mixed xylenes was identified,
11 Uchida, and one study examining subchronic effects of
12 p-xylene exposure was identified, Hake.
13 You described the Uchida study, but you didn't
14 describe the Hake study, and I was just wondering why that
15 was?
16 You go into detail about the Uchida study on the
17 bottom of 254.
18 DR. MARTY: Yeah.
19 We ended up using that study as the basis for the
20 REL, but I am not sure why we don't give more time to the
21 Hake study. We referred to it just another time, in another
22 paragraph.
23 DR. FRIEDMAN: I did not see any other reference to
24 it.
25 DR. MARTY: We just say it didn't include, it
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
192
1 didn't show renal effects.
2 DR. FRIEDMAN: It was not peer reviewed.
3 That's why you didn't review?
4 DR. MARTY: That could be one reason why we gave it
5 a short shrift, but we could add more in there.
6 DR. FRIEDMAN: Yeah, something needs to be said
7 because it raises the question, why did you mention it but
8 ignore it?
9 Page 254, a little nit pick, line 4 from the
10 bottom, talking about similar incidence of alcohol
11 consumption and cigarette usage: The correct terminology
12 there would be prevalence or maybe mean the distribution of
13 their usage, but not incidence would not be correct.
14 Page 255, I was confused right in the middle of the
15 page, near the end of that big paragraph, it said 10
16 subjective symptoms occurring in the previous three months
17 were significantly elevated.
18 I thought that could have happened, you did not
19 explain that that was away from the job, and I thought that
20 could have happened at the job, and it wasn't until later
21 that I discovered it was really away from the job, and
22 therefore, could be chronic effects.
23 DR. MARTY: Okay. We stated it later in the
24 section describing the REL.
25 DR. FRIEDMAN: Right.
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
193
1 I think it needs to be said there earlier, too.
2 Then in the derivation, on page 259, I was
3 wondering why you used ten-twentieths?
4 Why not one-half for ten-twentieth?
5 I didn't get why you used those particular numbers
6 to represent one-half?
7 DR. MARTY: Okay. That comes from the way we
8 adjust human occupational studies for discontinuous exposure.
9 It is assumed that in the eight hours that you work
10 in a day you actually inhale one-half of the air you would
11 breathe in a day. So, ten cubic meters out of twenty cubic
12 meters are breathed while active at work.
13 DR. FRIEDMAN: It was the volume of air?
14 I was thinking in terms of time.
15 DR. MARTY: It would be helpful to have the units.
16 DR. FRIEDMAN: Then my other question about the
17 derivation, why did you use the LOAEL uncertainty factor of
18 3, when you used 10 for others, such as tricholorethylene?
19 DR. MARTY: This reference exposure level was
20 developed in conjunction with the drinking water group, and
21 after a bunch of discussion, we ended up with the LOAEL
22 uncertainty factor of 3 rather than 10.
23 DR. FRIEDMAN: Somehow, it needs to be explained,
24 because it is sort of stuck out there, and it raises the
25 question.
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
194
1 I don't know if that is such a great explanation
2 that we arrived at that.
3 DR. COLLINS: At one place, we do say that it was
4 12 percent of the lifetime we used or more for the factor
5 one. If it was 8 to 12 percent, we used the factor of 3 and
6 7 years, and it is consistent in the beginning of the
7 document.
8 DR. MARTY: Jim, it is not a subchronic that we are
9 talking about.
10 Its the LOAEL uncertainty factor.
11 DR. FRIEDMAN: Regarding this, I had some comments
12 about your responses to the comments that you received?
13 MS MARTY: Okay.
14 DR. FRIEDMAN: On page 48, comment 4, odor may have
15 contributed to the subject of response results of exposed
16 workers.
17 It says Dalton, et al, recently demonstrated that
18 both perceived odor and cognitive expectations about a
19 chemical can significantly affect the reporting of health
20 symptoms, and you go into a whole dissertation about why that
21 may not be important, not very convincing.
22 I don't know why you just didn't say, and some of
23 this did not seem all that relevant, why not just, yes, there
24 may be some exaggeration of symptoms due to the association
25 of odor, and that is the limitation of the study.
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
195
1 DR. COLLINS: This is actually a legal brief by
2 Frank Mycroft, so he went through a lot of this, sort of over
3 done deal, but I think he is trying to make a point.
4 It has to do with negative versus positive, and it
5 did not influence it in the way it was expected.
6 DR. FRIEDMAN: Well, it is not a critical thing,
7 but I just felt it was over kill, and you could have said,
8 yes, that is a limitation.
9 Page 49, comment number 5, limited exposure data,
10 the Uchida study, assessment of workers exposure is similarly
11 problematic. Study relied on a single point estimate, one
12 eight-hour air sample, time weighted average and did not
13 indicate maximum concentration.
14 The authors admitted might have influenced the
15 subjective symptom prevalence, also, no evaluation for other
16 non solvent exposures were included. The workers may have
17 been exposed to such a material as in rubber boot production,
18 plastic coated wire production or printing, and then your
19 response was for each exposed worker in the study, Uchida, et
20 al, assessed exposure over the period of the entire shift,
21 below LOAEL of 14.2 is based on the geometric mean of 175,
22 such exposure measures taken on the day before the
23 questionnaire was administered.
24 The measurements and survey are, therefore, very
25 close in time. We, therefore, have high confidence in the
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
196
1 representativeness of these measurements.
2 It did not seem to me that closeness in time was
3 the question there. That was reassuring, but the question is
4 about representativeness of the chronic exposure.
5 Did the question there measure chronic exposure or
6 not, that is the question I raise?
7 You're just saying it was close to the time when
8 this one measurement was made, therefore we believe it. So,
9 I did not think that response was all that it could have
10 been.
11 Then on page 50, that is where I got concerned
12 about the description about the questionnaire during the past
13 three months being away from the job. It was only in your
14 response, that little short second paragraph, symptoms away
15 from the job, that I realized that was what that
16 questionnaire was about.
17 So, that is why I wrote a little comment there.
18 Again, then, the response on page 51, four lines from the
19 bottom, for several of the symptoms, while not at work,
20 again, that reminded me also that you had not said that in
21 the previous description.
22 That is it.
23 CHAIRMAN FROINES: Thank you, Gary.
24 Good. I think we will quit for the day.
25 That means, Melanie, we will take up the rest of
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
197
1 them --
2 DR. MARTY: October 6.
3 CHAIRMAN FROINES: Why don't we go a little bit
4 longer, and let him go through his chemicals then?
5 Peter has some of the most difficult compounds of
6 all. We have to be out of here at five o'clock.
7 Let's let him at least get started.
8 Let's see how far he can get, and then maybe since
9 Dr. Blanc is going to be doing a couple in the morning, maybe
10 let him finish in the morning.
11 Well, let's go until 5:00, then. It is only 20
12 more minutes.
13 DR. WITSCHI: I just looked through those for the
14 compounds, and actually, out of the 40, there are 13 where we
15 have an interspecies, uncertainty level of one, which means
16 where the data has been the reference for human studies, and
17 I was just wondering, looking at the same 30 compounds and
18 derive REL from the animal studies, because this would show
19 you to what extent would we get from animal studies versus
20 human studies, I mean if they do the animal studies over
21 estimate or under estimate, or is it going to be a mix,
22 because if you look now, how I came with this idea, if you
23 look to methyl chloroform, and you take the Mongolian Gerbil,
24 that is the most sensitive species, with a LOAEL of 70 PPMs,
25 and then you have some, page 158, some human studies where
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
198
1 people exposed to 110 to 345 PPM for a mean of 6.7 years,
2 nobody found any changes, no people, and then you are really
3 wondering if an animal is more -- if it is man, and then you
4 take the data, and in order to protect man, which is less
5 sensitive, you still apply uncertainty factor of 300.
6 In other words, we have a situation where man is
7 less sensitive than the animal, and yet you take the animal
8 data and apply to the animal data in order to protect man,
9 another factor of 300.
10 DR. MARTY: Well, I am not sure that you can say
11 that humans were less susceptible based on that.
12 Are you talking about Dramer, et al, 1978 study?
13 DR. WITSCHI: The Maroni study.
14 I mean here it says exposed 110-345 PPMs in air for
15 a mean of 6.7 years failed to identify neurotoxicity
16 resulting from methyl chloroform exposure.
17 Well, if you can show me that those people had
18 this, great. But you can always say what they didn't, too.
19 You can always say that in the absence of data.
20 But then if you go to the other one, now the chloroform,
21 again, we have cumulative uncertainty factor of 300, this is
22 page 41, and then somewhat down it says, the human
23 occupational studies have reported jaundice from 10 to 995
24 milligrams per cubic meter.
25 Well, this relates to the proposed inhalation
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
199
1 reference level only by a factor of 33. Here in this moment,
2 your value that is supposed to protect humans is only 33 away
3 from something that shows effects in humans.
4 So, there are the uncertainty factors, you may
5 underestimate, and just those two things brought me to the
6 idea, we have done this, now, we take what we think is good
7 data, and then we apply uncertainty factor, bingo, without
8 cross-checking, without doing some reality checks.
9 Therefore, I think if you would look at those 30
10 compounds and calculate the reference levels, also from the
11 best available animal data, see on both sides of the lines,
12 do they fold, all of them underestimate, all of them
13 overestimate, or is it going to be a hot spots?
14 Stan could help us with that one, but we could come
15 to some conclusion concerning hot spots, but do we get the --
16 DR. MARTY: Well, most of the time we actually did
17 do that, before we put together and decided which REL to put
18 in the document.
19 It is a scattergram --
20 DR. WITSCHI: I do not know based on what you rate,
21 the decision, the issue is really, is it justified to what
22 extent is it justified?
23 Just whenever we take animal data to apply those
24 uncertainty factors and to what extent are they real, if you
25 have human data, the inter species is consistently one.
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
200
1 Then the animal data seems to be your 10. I do not
2 figure out when it is 10 and when it is 3, but I do not even
3 know if they are real. We definitely, we think of the old
4 adage, and toxicology has it, man is 10 times more sensitive
5 than the most sensitive species, that is rubbage, but I think
6 that this book here would have data to allow for a critical
7 analysis of this question.
8 DR. MARTY: Well, I would be happy to do that.
9 I honestly don't know what it is going to tell you.
10 By the methods --
11 DR. GLANTZ: No.
12 What I meant by saying it was, okay, I mean I
13 think, I think that is okay that you don't know what it is
14 going to tell us, but I think it would be an informative
15 exercise to see the results.
16 So, I don't think it is worth discussing,
17 speculating about it, but I think it would be a factor, as
18 you said a couple of minutes ago, you have most of the
19 information already.
20 I don't know that it is something we would even end
21 up with in the final report, but I think it would be worth
22 bringing back to the Panel to help educate people about these
23 issues.
24 My guess is that it will probably be a scatterplot,
25 and it will say, okay, this is sort of best you can do.
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
201
1 But I think that looking at the question, it will
2 be interesting, and I think it will lead to better decisions
3 in the future, even if it does come up splattered all over
4 the place.
5 Then at least we can say if it was splattered all
6 over the place --
7 DR. WITSCHI: Well, if it is splattered or if there
8 is some pattern, that would lead to some better hypothesis --
9 DR. GLANTZ: I agree with that.
10 I don't think it is worth discussing any more right
11 now, because it is all just speculation, but I think it would
12 be a good thing to do, and I don't think it would be a lot of
13 work.
14 DR. WITSCHI: It is actually number crunching.
15 If I had a student, you would tell them what to do
16 with it, and you would wait for the results.
17 DR. COLLINS: We have board certified
18 toxicologists.
19 CHAIRMAN FROINES: I think this problem picking
20 human study versus the animal study runs through this entire
21 document, that there is clearly decisions made to go with
22 human studies wherever possible, and that is a policy
23 decision, and it may or not be correct.
24 I think that one has, where one has well-designed
25 toxicologic study, with careful attention to exposure, those
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
202
1 have become very valuable, given all the uncertainties
2 associated with exposure in human studies.
3 It seems to me that it is very worth while to look
4 at this issue. I will give you an example from my chemical,
5 hexane.
6 I think the study that you chose for hexane is
7 terrible. First place, you chose a human study that had
8 combined exposure with acetone, and acetone is known to be a
9 promoter or potential hexane neurotoxins.
10 You have animal exposure assessments that you
11 ignore, and you have a compound that has high dermal
12 absorption. You have nothing significant but uncertainty,
13 and that is a problem, I think.
14 You cannot choose a study where you have a combined
15 exposure with acetone and hexane.
16 DR. MARTY: Well, again, that was another one of
17 the USEPA RFCs.
18 We can go back and look at it.
19 CHAIRMAN FROINES: You are off the hook, Melanie.
20 When you choose a study, and that is EPA's, don't
21 choose a study that has flaws. You don't choose a compound,
22 hexane, whose neurotoxicity is potentiated by acetone, which
23 is a co-exposure.
24 On the face, that by itself would eliminate that
25 study.
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
203
1 DR. MARTY: Staff agree.
2 CHAIRMAN FROINES: You guys know about MEK, but in
3 fact, it is also true that acetone is a potentiator.
4 DR. GLANTZ: I think they agree with you.
5 My job at this meeting is keeping John up.
6 I'm the warm and fuzzy Stan today, but wait until
7 tomorrow.
8 DR. MARTY: We will come back on the sixth with
9 analysis of the 13 --
10 DR. GLANTZ: Are we tomorrow morning going through
11 the --
12 CHAIRMAN FROINES: No.
13 I think you were out of the room. We have the DPR
14 prioritization.
15 DR. GLANTZ: No. I understand that, but he won't
16 be at the meeting on the sixth.
17 CHAIRMAN FROINES: We will manage.
18 We have over a hundred of these things. He will
19 have more than enough time.
20 DR. MARTY: Also, doesn't Dr. Blanc think he is
21 coming back tomorrow to talk about the rest of his chemicals?
22 CHAIRMAN FROINES: Well, he is going to be coming
23 back anyway.
24 Wait. Stop. We have an Agenda Item that I want to
25 finish. Bill Lockett told me that we really had to finish
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
204
1 this Agenda Item, and since it will take 30 seconds, I can do
2 it.
3 All of you have the materials that we provided
4 about the Petition asking the ARB to Reopen the Scientific
5 Process for Listing of Diesel Particulate as a Toxic Air
6 Contaminant.
7 So, you all have that, and you also have, I
8 believe, the Response from Michael Kenny, that has declined
9 to Reopen the Scientific Process, and you also have other
10 documents that have emerged more recently, mainly Allen
11 Smith's paper, the editorial in the American Journal of
12 Public Health, and lastly the Response by Dan Greenbaum to
13 the formal Petition, as well as parts of the Petition itself.
14 The only thing I wanted to say to this Panel was
15 that one option that the industry has is to request a
16 Reconsideration by this Panel of the Diesel, of the listing
17 of Diesel Particulate, that is an option that could come
18 forward, and we have not received a Petition to date to do
19 that, but that could happen at some point in the future.
20 So, just the Panel is forewarned that that issue
21 could come up at some point in the future, and whether it
22 will or not, we have no way of knowing under the current
23 circumstances.
24 So, that is it, unless there is discussion about
25 it?
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
205
1 (Thereupon the Scientific Review Panel of the
2 Air Resources Board was adjourned
3 at 5:00 p.m.)
4 --o0o--
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345
206
1 CERTIFICATE OF SHORTHAND REPORTER
2
3 I, VICKI L. OGELVIE, a Certified Shorthand
4 Reporter of the State of California, do hereby certify:
5 That I am a disinterested person herein; that the
6 foregoing hearing was reported in shorthand by me, Vicki L.
7 Ogelvie, a Certified Shorthand Reporter of the State of
8 California, and thereafter transcribed into typewriting.
9 I further certify that I am not of counsel or
10 attorney for any of the parties to said hearing nor in any
11 way interested in the outcome of said hearing.
12 IN WITNESS WHEREOF, I have hereunto set my hand
13 this twenty-third day of September, 1999.
14
15
16
VICKI L. OGELVIE
17 Certified Shorthand Reporter
License No. 7871
18
19
20
21
22
23
24
25
PETERS SHORTHAND REPORTING CORPORATION (916) 362-2345