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

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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

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I N D E X

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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

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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.

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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

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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

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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

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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

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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,

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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.

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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

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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

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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

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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

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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.

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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.

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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

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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?

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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

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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.

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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

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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.

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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.

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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

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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

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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

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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

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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.

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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

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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

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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

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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

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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

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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

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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.

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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

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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

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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 --

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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

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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.

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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

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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.

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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.

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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,

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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

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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

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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

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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

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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.

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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.

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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.

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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.

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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.

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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.

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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

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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.

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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.

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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

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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

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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

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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,

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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.

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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.

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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.

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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

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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

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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?

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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

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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

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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?

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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.

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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,

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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

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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.

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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

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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.

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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.

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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

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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

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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

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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

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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

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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

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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

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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

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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

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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

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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

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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

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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

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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

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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

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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.

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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

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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

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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.

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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.

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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.

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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

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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

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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

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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

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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.

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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

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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.

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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

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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.

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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

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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.

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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

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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

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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

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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.

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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

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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.

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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

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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,

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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

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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

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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

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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

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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

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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

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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

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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.

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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.

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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,

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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

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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.

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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

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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.

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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.

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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

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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.

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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

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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.

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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.

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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.

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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

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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

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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.

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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

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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

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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

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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

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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?

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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.

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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,

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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,

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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

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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

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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

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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

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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

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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

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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,

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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.

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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

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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

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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

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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

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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

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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

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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

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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.

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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.

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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.

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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

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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

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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

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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

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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

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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

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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

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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.

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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

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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

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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.

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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

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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.

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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

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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

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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

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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.

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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.

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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.

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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,

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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

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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

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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

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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

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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

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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?

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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

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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.

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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.

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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.

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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

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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

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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

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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

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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.

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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.

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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

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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.

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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

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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?

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1 (Thereupon the Scientific Review Panel of the

2 Air Resources Board was adjourned

3 at 5:00 p.m.)

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1 CERTIFICATE OF SHORTHAND REPORTER

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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.

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VICKI L. OGELVIE

17 Certified Shorthand Reporter

License No. 7871

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