OSHA: Proposed Standard For Indoor Air Quality: ETS Hearings, January 19, 1995
OSHA: Proposed Standard For Indoor Air Quality: ETS Hearings, January 19, 1995
UNITED STATES DEPARTMENT OF LABOR
OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION
PUBLIC HEARING
PROPOSED STANDARD FOR INDOOR AIR QUALITY
Thursday, January 19, 1995
Department of Labor
Washington, D.C.
The above-entitled matter came on for hearing, pursuant to notice, at 9:00 a.m.
BEFORE: HONORABLE JOHN VITTONE
Administrative Law Judge
AGENDA
PAGE
R.J. Reynolds
Christopher R. E. Coggins
Michael W. Ogden
Paul R. Nelson
Stephen B. Sears
Michael W. Ogden
Christopher R. E. Coggins
Hoy R. Bohanon, Jr.
Questions:
Dr. Glantz 11848
Ms. Sherman 12000
Mr. Herman 12024
Mr. Dinegar 12121
Mr. Myers 12151
Allan Hedge
Questions:
Ms. Sherman 12170
EXHIBITS
EXHIBIT NO. IDENTIFIED RECEIVED
239 12021 12021
240 12022 12022
241 12022 12022
P R O C E E D I N G S
9:05 a.m.
JUDGE VITTONE: We resume our hearings into the proposed rule by the Occupational Safety and Health Administration for indoor air quality.
Before we resume our examination by the OSHA staff, let me repeat my admonition of yesterday. I would like to see questions more specific. I would like to see the answers more direct and specific to the question. There will be ample opportunity to clarify and amplify any answer in this proceeding. We made good progress, I thought, yesterday afternoon. If we can move along in that same mode all day, we should all be talking to each other by the time five o'clock or six o'clock rolls around.
DR. GLANTZ: In our effort to reduce the questions, a page got deleted by accident. Hold on a moment.
MR. GROSSMAN: While they're looking, Your Honor, Mr. Bohanon had an answer to a question that was posed yesterday.
JUDGE VITTONE: Okay. What question was that?
MR. BOHANON: The question had to do with the incident rates. I checked with our safety and industrial hygiene people and they inform me that the incidence rate is based on OSHA 200 type incidents and applies to all employees.
MS. SHERMAN: Hourly and salaried?
MR. BOHANON: Hourly and salaried. All employees.
MS. SHERMAN: Thank you.
MR. BOHANON: So that's the way that would be interpreted. If Dr. Coggins as a salaried employee had turned his ankle, then that would be counted as an incident.
MS. SHERMAN: Thank you.
JUDGE VITTONE: Thank you very much.
Ms. Sherman?
MS. SHERMAN: Yes. Dr. Glantz has some questions to ask and then I need to revisit some economic issues, Your Honor.
JUDGE VITTONE: Dr. Glantz?
DR. GLANTZ: Good morning. What I would like to do in the interests of trying to move quickly is first begin with some sort of general scientific issues and then once you set that, I think that will help us get through other questions more quickly.
Would you agree that properly applied mathematical modeling is a legitimate technique for use in science?
DR. COGGINS: I'll take a first stab at that. Properly applied --
DR. GLANTZ: I would hope you could say yes or no. I mean, I'm going to ask some more questions where you can elaborate.
DR. COGGINS: I really don't think that's a yes or no answer. It's a very big question. Properly applied and what kind of mathematical modeling.
DR. GLANTZ: Well, I'll get to that. I'd like to talk about mathematical modeling as a general approach to science. I mean, people teach courses in that. And then I want to get to the question of what properly applied means but would you agree that properly applied mathematical modeling is a legitimate technique in science?
DR. COGGINS: It may be.
DR. GLANTZ: Well, do you think it is or isn't?
MR. GROSSMAN: I think you got an answer. Why don't you move ahead?
DR. COGGINS: There are models that work and models that don't work.
DR. GLANTZ: Well, I want to get to how you decide a model works or doesn't work.
JUDGE VITTONE: Let me ask you this. Is this a technique that is used, has been used in the past, by scientists or mathematicians or whatever?
DR. COGGINS: I'm still not sure exactly what the question is. There's a number of mathematical models that's been used for example in Mr. Bohanon's area. We've talked about Dr. Nelson's area.
DR. GLANTZ: I'm not talking about a specific model yet. I'm trying to establish some general principles rather than getting bogged down in a lot of -- we'll get to the specific models. But, as the judge said, is that a general technique which properly applied is accepted in science? I take it is since you're using it in some cases and you would deem those to be proper applications.
MR. GROSSMAN: Maybe to clarify this, are you asking whether mathematical modeling properly applied is accepted in all scientific disciplines or in some scientific disciplines?
DR. GLANTZ: In scientific disciplines where it's used. This is -- you're making a very straightforward question very complicated. It's not a trick question. I promise.
DR. COGGINS: Well, I understand it's not a trick question. But you're now saying is mathematical modeling a technique in areas where it's applied. I mean, that seems to be a circular kind of question.
DR. GLANTZ: No, there are some people who would say -- I mean, I know a few people who say that you can never do mathematical modeling, that it's ridiculous. But I'll try to --
It's going to be a long day, Your Honor, I'm afraid.
JUDGE VITTONE: No, it won't. No, it won't.
Why don't you go directly to your question?
DR. GLANTZ: In getting to the question of how one determines if a model is properly applied, is one of the things you need to make that judgment an understanding of the assumptions that are in the model?
DR. COGGINS: I think that's a much better question. I think yes.
DR. GLANTZ: Okay. And --
DR. COGGINS: Just a second. I really need to finish that because obviously there are a great deal of a number of assumptions in any model and you've got to know all of those.
The other part you need to also be aware of is are there other assumptions that you haven't taken into account.
DR. GLANTZ: Yes. In order to judge whether a mathematical model is properly applied, do you need to know the precise equations in the model or computer code that's used to implement the model if there are no explicit equations written down?
DR. COGGINS: Do we need to know the precise equations to go into the model?
DR. GLANTZ: In order to judge whether or not you think it's a correct model or proper model.
DR. COGGINS: Can you help me on this, Steve?
DR. SEARS: Yes, I'd be happy to.
In my opinion, Dr. Glantz, yes. The answer is yes. In order for me to evaluate both the validity of the model and the application of the model, I would need to see the equations and whatever coding has been performed to execute it.
DR. GLANTZ: Would you say that in order to judge whether or not a mathematical model is an accurate model properly applied you need to see the data that was used to validate the model and how well the model fit that data?
DR. COGGINS: I think I would like to see both sets of those.
But, again, Steve, you're more the expert in this area.
DR. SEARS: Yes. I would like to see both of those. However, I can think of some exceptions where that may not be possible.
MR. BOHANON: Certainly in the engineering field there are cases where there are applied models in control theory where it's not necessary to understand the data that generated that control model but simply necessary to understand that the control works in the applied situation.
DR. GLANTZ: So to just clarify what you said, would it be then -- you're saying that still to use a control system you would want to verify that it behaves the way you would hope it would, if you're dealing -- I mean, if it's a simple control system, but if it's a complex control system, people usually do some sort of testing to verify that it's behaving as expected, wouldn't you say?
MR. BOHANON: Yes. And that can be a judge of the performance in that field of application.
DR. GLANTZ: And then would you say that it's fair to say that after you have gone through these -- well, I'm getting ahead of myself.
If one develops a model for one situation, would you say that it is fair to conclude that very often the conditions in which the model is applied, you need to be careful not to go beyond the areas that the model was originally developed for? Maybe a little bit beyond but not very far afield. If you're being very careful. Would you agree with that?
DR. COGGINS: I think that in many situations where you have multiple parameters in your model minor changes in one parameter can have wild effects on the overall conclusion.
Steve?
DR. SEARS: Certainly there are models where extrapolation is appropriate and interpolation. And, of course, there are models where not even interpolation is appropriate.
MR. BOHANON: And in the engineering field there are cases certainly where you go beyond the parameters that the control was designed for and the system becomes unstable.
DR. GLANTZ: Okay. Well -- okay. Thank you.
We'll come back to this in some specifics later but I want to just go through some general science at the beginning.
I would like to just address some general principles of toxicology. Have you by any chance read the August 5th Notice of Intent to Appear by the Washington Technical Information Group? Any of you.
DR. COGGINS: I glanced at it. It's been a while. I haven't read it recently.
DR. GLANTZ: It's my understanding -- actually, I read it myself, they submitted a chapter from the Cassaret and Doull toxicology textbook in that submission. Are you familiar with that book or the chapter the put in there?
DR. COGGINS: There are four separate editions. I don't know which -- presumably the most recent.
DR. GLANTZ: But you are generally familiar with the book.
DR. COGGINS: Absolutely.
DR. GLANTZ: Okay. Would you say it's an authoritative text?
DR. COGGINS: It's a toxicology text. There are many others.
DR. GLANTZ: Well, in any event, the Washington Technical Information Group characterized it as, "The most authoritative text" and perhaps the most authoritative textbook in the field. So they at least were impressed with it.
In chapter two of the book by Claussen and Eden, they describe the presence of a dose response relationship as "the most fundamental concept in toxicology." Would you agree with this principle or with this statement?
DR. COGGINS: Not necessarily. I think it is a general principle of toxicology, that you would expect a dose-response relationship but that there are many other factors that are involved in toxicology than just a simple relationship between dose and response. I think that's an oversimplification.
DR. GLANTZ: Well, briefly, what are some of the other principles that you think are important? We're all trying to be brief.
DR. COGGINS: Well, that's again a very big question. The main point I think I would make in terms of general toxicology is something we've heard a lot of and that's the statement by Paracelsus that the dose makes the poison, which is the inverse, if you like, of your statement of dose-response, but that anything could be made into a poison, it's just a question of supplying enough dose. That's certainly one founding principle of toxicology, one that's been with us for 400 years.
There are many other aspects. We could talk about toxicology textbooks for a long time.
DR. GLANTZ: Okay. When was this statement you made about the dose made the poison, when was that statement made?
DR. COGGINS: Paracelsus made it, I believe, 1567.
DR. GLANTZ: Was he a cancer toxicologist?
DR. COGGINS: He was a German pharmacologist. I don't think the word toxicologist was around then.
DR. GLANTZ: Well, getting back to the textbook we were talking about, there's a chapter there, chapter 5, titled "Chemical Carcinogenesis." Are you familiar with that?
DR. COGGINS: I have probably read it but not recently, certainly.
DR. GLANTZ: Well, in chapter 5 under the section "Quantitative Aspects of Carcinogenesis" it says, "Thus, with DNA reactive genotoxic carcinogens, a given dose can result in permanent abnormalities of cells. Subsequent dosages can add to such changes." Do you agree with this statement?
DR. COGGINS: I think the operative work in there is can. There are many other factors that are involved. The textbook that you are referring to is, of course, a textbook and is therefore upon the day it was printed is probably out of date.
One of the statements I was making yesterday, there is some very recent work on DNA repair, I think something we would want to make as a very strong adjunct to the statement that you have just made.
DR. GLANTZ: But as far as -- I didn't make it, the textbook made it. But do you agree? I still don't understand if you agree or disagree with this statement. It's obviously not everything that could possibly be said but is this statement a correct statement as far as it goes?
DR. COGGINS: Well, I think I will stick with the statement I made, the key word is can.
DR. GLANTZ: Okay. The same section in this textbook which was published in 1991 says, and I'm quoting, "Thus, time as well as dose is a factor in assessing the properties of chemical carcinogens." Do you agree with that statement?
DR. COGGINS: Yes. I think that particularly in the field of inhalation toxicology, which is, of course, my expertise, that the equation C times T is of major significance.
DR. GLANTZ: The same section further states, "A number of small doses may give no immediate evidence of their action but in time they could yield neoplasms within the life span of the host." Do you agree with this statement?
DR. COGGINS: I don't want to sound obstructive, but, again, that word may, it may, it may not. It seems to me a very narrow statement with that word may in the middle. In some circumstances, yes, in others, probably not.
DR. GLANTZ: The same section also states that when a chemical "is administered as smaller doses over a longer period of time it can actually be more effective than when it is given as larger yet fewer individual doses in a shorter period of time." Do you agree with that?
DR. COGGINS: This is starting to sound like a litany. May, can -- in certain circumstances, yes. Under other circumstances, no.
DR. GLANTZ: What are the circumstances in which you would agree and disagree with this statement from this textbook?
DR. COGGINS: We could take a simple example, not necessarily referring to neoplasia but for example one of the classic sets of equations, and I guess it comes back to your very first point about mathematical modeling, would be for the uptake of carbon monoxide, that if you gave an absolutely massive dose of carbon monoxide, let's say 10,000 parts per million and you gave it for five minutes, clearly everybody would die. If you gave 2 parts per million for 20 days, nobody would die. And yet you could develop a mathematical model for C times T, concentration of CO and the time that you expose those people and, indeed, the Coburn-Foster-Kane equation has been derived for different concentrations, different times of how that would result in the ultimate problem of cause of death. So that is an example of where you need to develop a mathematical relationship between C and T, concentration and time.
DR. GLANTZ: Okay. But could you give us an example of a carcinogen where you think the statement here was correct and true and if you would like one word isn't correct?
DR. COGGINS: No, you've used a word in a way that I don't use it and I want to define my usage before I can even continue on that question.
A carcinogen is not a carcinogen. It is not an inherent property of a material like molecular weight or boiling point. You can only define the carcinogenicity of a compound by correct reference to four different parameters. That's the test species, that's the dose of administration, that's the dose used, and the target organ.
Now, only when you have defined those four parameters for me can I answer any questions on carcinogenicity.
DR. GLANTZ: Okay. Well, I'd like you to give me an example of a carcinogen where you think the statement that administered as smaller doses over a longer period of time it could be more effective than when given as larger yet fewer individual doses in a short period of time. Using your definitions.
DR. COGGINS: Given time, I could come up with such an example but under these glaring lights I can't think of one off hand.
DR. GLANTZ: Having been under the glaring lights, I would ask you to submit that as a post-hearing comment. And I am particularly interested in an example of a carcinogen which administered as a smaller dose over a long period of time is actually more effective than when given as larger yet fewer individual doses over a short time. And when I say more effective, I mean more likely to end up inducing a cancer.
If you would like to also submit an example where that isn't true, that would also be interesting, but I am most interested in one where you think those conditions are met. And you could submit that as a post-hearing comment.
DR. COGGINS: Could I just confirm, then, you want me to give you an example of a known carcinogen, which I will define with the four parameters that I've just given you, that given in small concentrations over a long period of time can produce a higher or lower response than a carcinogen given in high doses over a short period of time?
DR. GLANTZ: No, I want one which will -- well, you'll have a transcript to work from but I want one which, and I'll read the quote from the book again, it says there are chemicals which "administered as smaller doses over a longer period of time can actually be more effective," and by effective they mean effective at inducing cancer, "than when given as larger yet fewer individual doses in a short period of time."
And that's what the textbook says and what I would like is an example of a chemical where you believe this statement is a true statement with regard to that chemical using your definitions, which I think are acceptable for this.
DR. COGGINS: I'll do that but I will add to that the comments that I made earlier of the problems that you have when you have low dose administrations where you can have a massive amount of DNA repair that is overwhelmed by the higher concentrations. This concept of linear extrapolation from high dose to low dose as I mentioned in testimony yesterday is under severe examination in toxicology circles, so I'll add that to my comment.
DR. GLANTZ: Well, that's fine but I think you understand what we're asking for --
DR. COGGINS: I do.
DR. GLANTZ: -- so I'm going to move on.
Then the last sort of general questions, or actually there are two more, let's suppose we're doing a laboratory as you do in college where I'm going to give you a vial with some purple substance in it and I know what it is and you don't and I know that it is a carcinogen by your definition, let's just say to make it relevant to the proceedings that it's a lung carcinogen when inhaled, and I know that for a fact, okay?
And I give this vial to you and say, Dr. Coggins, I want you to figure out whether this is a carcinogen when inhaled over a long period of time at relatively low doses but I know it is, we'll call it Glantzium.
How would you go about determining that? I know what the outcome is, you don't, but what set of experiments, and as briefly as you can although I realize it's a difficult question, what series of steps as a toxicologist would you go through to reach the conclusion that this purple fluid is in fact carcinogenic?
DR. COGGINS: Well, of course, this is a hypothetical question.
DR. GLANTZ: Yes, that's correct.
DR. COGGINS: And as such maybe I shouldn't answer it but you didn't mention one important aspect. You say it's a known lung carcinogen by inhalation. You didn't mention the species.
DR. GLANTZ: Well, let's just say in rats.
DR. COGGINS: Okay. So you're omniscient.
DR. GLANTZ: But I'm not telling you the rats. I'm omniscient, I know it is, I've just handed you this vial of material and I'm saying to you, Dr. Coggins, as a toxicologist, you tell me is this a carcinogen, a lung carcinogen, when inhaled. But beyond that, I've told you nothing. And so how -- I mean, if you were teaching a toxicology course, you know, and this is a laboratory exercise, what series -- there's a series of steps I think most toxicologists would go through to evaluate this purple thing when you aerosolize it or something and I'd like you to as briefly as you can go through the series of steps that you would take. You don't know it's a carcinogen. I know it is. So I know ultimately you could get a positive result but what would you do?
DR. COGGINS: This is a fairly long question. I now have Glantzium in a jar.
DR. GLANTZ: Yes.
DR. COGGINS: And I've been asked to perform a carcinogenicity assay? Or what --
DR. GLANTZ: I've come to you. I don't know anything about toxicology. I say I got this stuff and I want to spray it into the air because it's a perfume or something and I have crazy environmentalists out there saying that this is bad. Tell me whether it's bad or not, whether or not this causes cancer.
DR. COGGINS: Okay. Now that you've narrowed it down, that makes more sense.
DR. GLANTZ: Okay.
DR. COGGINS: The very first thing I would do, I would take Glantzium and I would give it to my colleagues the chemists and I would ask them to tell me what's in it. And they would analyze this material and come back and say it contains compounds X, Y and Z at concentrations A, B and C.
I would then ask you of the sponsor the route of administration because if I was to swallow Glantzium, I would take a very different set of tests --
DR. GLANTZ: It's inhaled. It's inhaled as an aerosol.
DR. COGGINS: So you're now telling me that I would be involved in inhalation of the compounds that I now know are present in Glantzium.
I would then go back to the database of toxicology and say are compounds A, B and C at concentrations of X, Y and Z, I transposed it, are there any data on those, what are the toxicological responses obtained in these compounds in these materials that are present in Glantzium and I would then at that point make a decision as to whether any further studies were needed.
If there were data in the literature that indicated carcinogenic effects or non-carcinogenic effects, I would then be at a decision point in my tree, my decision tree. If there were hard and fast data, I would come back to you and say take it back. So it's a lung carcinogen.
If there were no data, which I think is the point of your question, I would then probably, depending on how much time and money we had, initiate a series of toxicological studies to determine what exactly the responses of Glantzium would be in experimental animals. Probably the first study, the first experimental design, would be very similar to the 14-day study I described yesterday. But, again, I would have to work very closely with my colleagues the chemists who would tell me exactly how much material that I have presented to the animals, whether or not the material can be inhaled under the circumstances that I had defined. And then I would look at those responses and see what my colleagues as toxicologists would think of the results of the examination of Glantzium.
At the same time, while I'm doing this, I think I would be looking around and talking to colleagues such as epidemiologists to say are there examinations of Glantzium in the epidemiological sense. In other words, are there, for example, work situations where people have been exposed to Glantzium.
DR. GLANTZ: Would you then --
DR. COGGINS: I'm not finished.
DR. GLANTZ: I thought you were done.
DR. COGGINS: We're a long way off.
DR. GLANTZ: Okay.
DR. COGGINS: So what I'm trying to build here would be a consensus of opinion to arrive at the word that we used yesterday, cause. Because I'm now building up the consensus of opinion from the epidemiologists, from the chemists and from the toxicologists, we'd be moving forward on, if you like, three parallel paths to obtain information on Glantzium.
I would probably at this stage initiate -- depending on the results of the earlier studies, some longer term studies, depending on the results, as I say. We would be possibly considering a long-term inhalation study depending on the results of the earlier term studies.
So that hopefully when we've got the information back from my colleague the epidemiologist who would say there's a link or there isn't a link, the chemist would say there's something in here, there isn't something in here, looking back at the database, there's something in here, there isn't something in there, and, of course, depending on the results of the toxicology assays, I'd come back to you and give you my consensus opinion as to the toxicological activity of Glantzium.
I'm sorry it's such a long winded answer but it was a big question.
DR. GLANTZ: No, I appreciate that. I would just like to, despite the long answer, ask you to elaborate one or two points.
Could you give me a little more details on how you would do the toxicological testing? And, in particular, let me try to ask you a few specific questions.
Would you determine an LD-50? Again, you know nothing about this to begin with.
DR. COGGINS: The concept of LD-50 in inhalation is not really applicable because of the C times T concentration thing I was just describing, for example, with CO.
DR. GLANTZ: Well, how would you -- since all I've given you is this vial of stuff, how would you decide what doses what you might want to use in your inhalation experiments?
DR. COGGINS: I would look at the database of toxicology results.
DR. GLANTZ: You can't find -- nobody's done it, it's a new -- you don't -- you can't -- there's nothing in the database.
DR. COGGINS: We're getting more and more hypothetical as we go on. You're narrowing me down. I'm saying that I would look at the information from my chemist colleagues, and I think it's pretty unlikely -- they aren't going to come back and say you've got a new compound here. I'm sure there's going to be some information on comparable compounds or families of compounds. I'm going to look at those data and from those perhaps construct a dose range finding study and that basically was what the 14-day study that I described yesterday was, was a dose range finding study to see what the approximate toxicological end points were in a study with a material that had not been examined in the literature.
Just now getting back onto the point here, when we performed the 14-day study almost six years ago now, there were very few references in the literature to inhalation studies with real ETS. In fact, there weren't any. So we were effectively working in the dark under that very same set of hypothetical statements that you've just made. And we decided that based on these chemists and their ideas of what would be a reasonable exposure to perform exposures of that and ten and hundredfold exaggerations.
So when we were doing the 14-day study with ETS, we had no idea what the responses were likely to be at those concentrations, although we had a rough idea compared to mainstream smoke but, of course, we've heard from again the chemists, it's very different.
DR. GLANTZ: Okay. Thank you.
I'm going to try to ask you a few pointed questions that I hope you can give much shorter answers to.
Would you say that an accepted toxicological procedure is to determine an LD-50 for a compound and then based on that back off from that and determine what exposures would be appropriate in a long-term inhalation study?
DR. COGGINS: I think the concept of LD-50s is outdated, outmoded and is not really of great relevance to toxicology. It's perhaps of relevance to acute toxicology but I don't think that an LD-50 is necessarily of major importance in the armamentarium that toxicologists have.
DR. GLANTZ: Now, yesterday when we were talking about some of these same issues, we were talking about long-term studies, the 24-month studies. You made the point that sometimes you people even do 30-month studies now. Would you say that it is common practice to do a long-term study, 24, 30 months if you're talking about a rodent, and then back off the exposure duration? That that's often the way people do toxicological bioassays or cancer bioassays, is to begin with a long-term exposure study and then work their way back down to shorter terms?
DR. COGGINS: No, the exact opposite. You start with a short-term study and see what the responses are and see if they warrant further attention. You have a kind of a battery approach. You would start off with a short-term study, an acute study, say like a 14-day dose range finding. Depending on what you saw there, what the indications were, you would go to a longer term study, which is exactly what we did with ETS. Then when you've got the 90-day data, you look at that and say, well, are there any indications here based on my information as a toxicologist and on the information that I have seen in the literature that those changes would warrant a longer term study.
And, in the case of our 90-day study, that one change that we saw, hyperplasia, which I'm sure you'll agree is a very minor change, in a tiny portion of one area of one organ only, we just felt that that was not, and I feel today that that is not the kind of lesion that is going to progress to a carcinogenic end point in a two-year study or to any other kind of response in a two-years study.
DR. GLANTZ: Well, I didn't want to get into that specific study quite yet but in terms of the statement that you just made, that was your belief, though. You don't have any data to demonstrate that that's a true statement, that's just what you believe based on your best scientific judgment, is that a correct statement on my part?
DR. COGGINS: Based on my scientific judgment and on that of my colleagues, the fact that the response that we saw in the 90-day study was the same as that seen after four days and based on my previous statements that responses after 90 days are the same as after two years, we felt that there was no real reason to move into the next stage of the battery. Because then --
DR. GLANTZ: Okay. You've answered the question.
When people are doing bioassays for chemical carc