OSHA: Proposed Standard For Indoor Air Quality: ETS Hearings, January 12, 1995

OSHA: Proposed Standard For Indoor Air Quality: ETS Hearings, January 12, 1995


UNITED STATES DEPARTMENT OF LABOR

OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION

PUBLIC HEARING

PROPOSED STANDARD FOR INDOOR AIR QUALITY

Thursday, January 12, 1995

Department of Labor

Washington, D.C.



The above-entitled matter came on for hearing, pursuant to notice, at 10:00 a.m.

BEFORE: HONORABLE JOHN VITTONE

Administrative Law Judge

AGENDA

PAGE

Consultants in Toxicology

Gordon W. Newell 10965

Questions:

Ms. Sherman 10974

Mr. Klock 11021

Mr. McNeely 11031

Judge Vittone 11042

Mr. Andrade 11045

Ms. Sherman 11066

EXHIBITS

EXHIBIT NO. IDENTIFIED RECEIVED

221 11070 11070

P R O C E E D I N G S

10:15 a.m.

JUDGE VITTONE: We resume hearings today into the proposed rule on indoor air quality by the Occupational Safety and Health Administration.

Our first witness is Dr. Newell.

Sir, would you come forward, please?

(Pause)

JUDGE VITTONE: Good morning, sir.

DR. NEWELL: Good morning, Your Honor.

JUDGE VITTONE: Would you state your full name, please?

DR. NEWELL: I am Gordon W. Newell, and I'm appearing here at the request of Philip Morris.

JUDGE VITTONE: What's the name of your company?

DR. NEWELL: Consultants in Toxicology.

JUDGE VITTONE: Okay, sir.

How long is your presentation going to be?

DR. NEWELL: Fifteen minutes or a little less, perhaps.

JUDGE VITTONE: And you have one slide?

DR. NEWELL: One overhead.

JUDGE VITTONE: Whenever you want to do it, we'll slide that thing out there.

DR. NEWELL: Sure.

JUDGE VITTONE: If you're ready, you can begin.

DR. NEWELL: Thank you.

I am Dr. Gordon W. Newell, consulting toxicologist.

Earlier, I was asked by Philip Morris to comment on and review the animal studies which address the issue of tobacco smoke and lung cancer as cited on OSHA's rulemaking, regarding indoor air quality.

I wanted to emphasize here, however, the views and the opinions expressed are mine and mine alone.

Your Honor, I am pleased to have the opportunity to testify here today on certain aspects of the OSHA proposed rulemaking governing indoor air quality in the workplace.

I obtained my PhD in Biochemistry from the University of Wisconsin in 1948, after which I served for two years as a biochemist and coordinator of clinical studies at Wallace & Turnen Company in New Jersey.

Although toxicology was not recognized at that time as a scientific discipline, it turned out that my thesis work involved the study of a toxic component formed in wheat flour during processing and prior to baking. The isolated chemical was found to cause convulsions and running fits in dogs.

In 1950 I joined the staff of the Stanford Research Institute, now known as SRI International. During the ensuing 28 years, I directed the development of one of the first research and testing toxicology departments in the country, which included aquatic toxicology as well as in vitro and in vivo mutagenesis laboratories. The staff grew to a core of more than 50 professionals and technical support personnel.

From 1978 to 1982 I served as Associate Executive Director, Board on Toxicology and Environmental Health Hazards, the National Research Council, National Academy of Sciences. Here, studies were conducted by expert committees on health issues as requested by Congress, as well as various departments and agencies of the government.

In 1982 I returned to California and assumed the position of Senior Program Manager for Health Studies at the Electric Power Research Institute. Programs studied here included the biological effects of electromagnetic fields, occupational risk assessment of PCBs, the biological significance of coal-produced fly ash, and other subjects.

Since 1988 I have been a consultant in the area of general and environmental toxicology.

The comments I offer today are based on my experience as a scientist and research manager, as well as extensive services and advisory roles to numerous public and private organizations. These have included, among others, service on various EPA advisory and review committees, members on the Science Advisory Board of the National Center for Toxicological Research, member of the Board of Directors of the Toxicology Laboratory Accreditation Board, and a member of the administrative panel on laboratory animal care for more than six years, the Stanford Medical School, as well as numerous other activities.

Among my professional members are the Society of Toxicology, member and chair of various committees; the American College of Toxicology, former president and counselor; the Environmental Mutagen Society, also a former president and counselor; Society for Risk Analysis, member of the organizing committee and a member of its initial scientific advisory council; and I am pleased to be a Fellow in the Academy of Toxicological Sciences. This is a peer recognition society based on one's contributions to the field.

I've served on the editorial boards and as a peer reviewer of manuscripts for various scientific journals, including risk analysis, regulatory toxicology and pharmacology, inhalation toxicology, mutation research, and food and chemical toxicology. I have published over 80 scientific papers, authored some 200 scientific reports for clients, have been an invited speaker at many and numerous international meetings and conferences.

On July 15th I submitted a written statement of my views to the record. That submission included commentary about each of the animal studies cited by OSHA as evidence that environmental tobacco smoke, that is ETS, should be recognized as a primary carcinogen for lung cancer, and my reasons why such a designation was improper.

Today my comments will be focused on the broader aspects of acceptable experimental design and the test parameters which have become the basis for regulatory decisionmaking. I'll also touch on certain animal studies cited in the OSHA document on indoor air quality, plus other relative animal studies. Because there are only a few animal experiments which have investigated ETS as such, much of the OSHA literature citations involve experiments with direct exposure to tobacco smoke.

I have conducted an in-depth review of the animal studies cited in the referenced document, as well as other relevant animal smoking studies. From my review of the available research papers, I conclude the data are insufficient to support a finding that an association exists between environmental tobacco smoke and lung cancer.

Let me repeat that. From my review of the available research data, I conclude that the data are insufficient to support a finding that an association exists between environmental tobacco smoke and lung cancer. And from the numerous cigarette inhalation studies with mice, rats, rabbits, dogs, hamsters, monkeys, ecologically realistic animal studies have generally failed to support the hypothesis that fresh tobacco smoke causes lung cancer in these species.

Taking into account the previous statement, it is difficult to conclude that ETS, a product of lesser concentration and of different composition than mainstream tobacco smoke, could cause cancerous lesions in the lung.

For the proposed regulation concerning ETS to be credible, it will have to be supported by adequate and factual health data to justify the establishment of standards.

It is here where I have difficulty in agreeing with OSHA's interpretation of ETS as a primary lung carcinogen. When a regulation is established, it must be based on verifiable information which can be repeated by others. Thus the need for criteria and standards.

Today I have one visual overhead for you.

(Slide shown)

In this overhead there is presented the basic criteria which the NTP uses in the design of studies to define whether material is to be classified as a carcinogen. The EPA relies on the NTP to identify carcinogens through the use of established standards. These standards must be met with identifying carcinogens, which subsequently will be listed as health hazards in the occupational environment.

You will see there, these are just some of the basic criteria. There are many more detailed aspects that the NTP requires to be followed in conducting any of their bioassays. It requires an experimental design that is well conducted. Well conducted means that the animals are housed under the general standards that the National Academy of Sciences in their report on the use of animals, is necessary. In fact today unless you get approval and accreditation through AAALAC, the American Association and Accreditation of Laboratory Animal Care, you probably would not be able to qualify to even do any of the studies for NTP.

According to these criterion today, you need at least three dosage groups so that you can demonstrate if there is a response, it's a dose-related response, and have adequate numbers of animals of both sexes of each, both mice and rats. As you can see, they want to be able to see if it does cause malignancies, that these are dose-related. Also, the NTP uses, although I don't necessarily always agree with it, but it's in their basic premise that a combination of benign and malignant neoplasms is a way to also justify whether or not a material is considered as a carcinogen.

That's all we need on that.

JUDGE VITTONE: Excuse me doctor, could you wait one second?

DR. NEWELL: Surely.

(Pause)

DR. NEWELL: May I say that none of the animal studies cited in the OSHA document on indoor air quality meet the criteria for establishing the carcinogenicity of a test substance, in particular, ETS.

It is appropriate here to review the several tobacco smoking studies that have been conducted with beagle dogs. First of all, let me say there are number of investigations which are reported in the literature and have been demonstrated that the beagle is susceptible to chemical carcinogens, with the resultant development of lung cancer. Particularly, a reference is cited from Health Physics, Volume 42, page 33, 1987.

Auerbach et al conducted two smoking studies with beagles. Conclusions from the first study claimed the dogs developed interstitial fibrotic and granulomatous lesions. I have discussed this particular study in my written submission earlier.

A review of the histopathology by J. L. Abrams at UCLA, that's the University of California at Los Angeles, and the American Review of Respiratory Diseases, Volume 119, page 197, 1979, showed the presence of magnesium silicate particles, that is talc, in the lung tissue -- not tumors.

Another reviewer of the Auerbach study, a paper by Herst and Hattendorf which appeared in Veterinary Pathology in Volume 10, page 385 in 1973, noted that dogs used by Auerbach came from the same breeder as used by the reviewer. This reviewer stated that they histology of the lungworm lesions in his dogs' lungs were similar to the histopathology noted by Auerbach.

It's interesting also that a second two year study with beagles, and also these dogs were tracheotomized, by the Auerbach group, a paper being authored by Fraska, Auerbach et al, and it appeared in Experimental Molecular Pathology, Volume 21, page 300 in 1974. This paper made no claim of carcinogenesis due to chronic exposure to cigarette smoking. Further an NCI-supported cigarette smoking study with tracheotomized beagles initiated at Battell Northwest Laboratories in Washington State, and subsequently moved to the Bornstein Laboratories in Maryland, was terminated after six years of exposure when no carcinogenic effects had been noted. Although the government promised to provide a histopathology report on the dogs in the study, after more than ten years, none has appeared.

Also an NCI smoking study initiated in 1978 with tracheotomized beagles at Hazelton Laboratories America, Vienna, Virginia, was discontinued after two years. Extensive histopathology studies were done on various tissues, but there were no adverse effects on the cardiovascular system due to the experimental design which included cigarette smoking, added carbon monoxide, and the use of low and high nicotine containing cigarettes.

Also, there was no mention of lung tumors in the smoke-exposed beagles. Results of the study have never appeared in a scientific journal. It was only through the use of the Freedom of Information Act process with a summary report through NCI made available.

My main purpose in appearing here today is to emphasize the importance of quality research, where a goal of such research is determined if a biological effect due to treatment may occur, and if an effect is demonstrated is it repeatable with an evident dose response? Often experiments are undertaken in an attempt to cause an adverse effect. Such experimental efforts are far from objective, a really prejudicial effort.

Most of the studies referenced in the April 5, 1994 OSHA proposed rulemaking document, were not conducted with ETS, did not demonstrate the development of malignant lung tumors, did not approach the basic material used by the National Toxicology Program for investigating possible carcinogenicity, nor is there available a long term study which has investigated the potential carcinogenicity of ETS.

Thus in my judgment, OSHA's position that ETS is a primary lung carcinogen is scientifically insupportable.

Thank you.

JUDGE VITTONE: Thank you, sir.

Ms. Sherman?

MS. SHERMAN: Yes.

JUDGE VITTONE: Excuse me, can I have that slide?

DR. NEWELL: Sure. I have a hard copy if you'd rather.

JUDGE VITTONE: Yes.

Okay, Ms. Sherman. I'm sorry.

MS. SHERMAN: Thank you.

You attended the University of Wisconsin in Madison?

DR. NEWELL: I did. That was the only University of Wisconsin campus at the time.

MS. SHERMAN: Well, I did too.

DR. NEWELL: Good. Good company.

MS. SHERMAN: Yes.

JUDGE VITTONE: Lousy football team.

(Laughter)

MS. SHERMAN: I noticed that in your notice of intention to appear you said you were a PhD, and then F-ATS. What is...

DR. NEWELL: Academy of Toxicological Sciences. I referenced that in my presentation.

MS. SHERMAN: F dash...

DR. NEWELL: Academy of Toxicological Sciences, ATS.

MS. SHERMAN: Okay.

What is that Academy for Toxicological Sciences?

DR. NEWELL: That is a peer recognition society which has established criteria for recognizing those people that are considered leaders in the field of toxicology. It is not an organization which brings people to it on the basis of a test, but rather on the basis of performance and what people have done in terms of publications, participation, and scientific activities, recognition by their peers, such as on various advisory committees, be they for NIH, EPA, or even in the private sector. All these things are put together on a factor rating of up to 100 points. Those people that get 70 or more points, they're accepted into the society.

Every five years, one is requested to resubmit what they've been doing in the interim, in order to make sure that you're still an active member of the field.

MS. SHERMAN: For how long have you been a member of this organization?

DR. NEWELL: A member as such, as being accepted. I think it's about seven years now. However, I was a part of a group that actually was involved in organizing this society. I was part of that for probably seven or eight years. Then when it was thought appropriated, and suggested that I should consider becoming a member, I withdrew from any participation and let the judges make their own decision.

MS. SHERMAN: Is this a society where one self-nominates, or must one be nominated by a peer?

DR. NEWELL: The organization has an application form and you feel free to fill this out. However, any applicant is given guidance with regards to the kinds of criteria that they must meet, and they're discouraged to even apply if they don't really feel like they meet the four basic parts of the criteria selection.

MS. SHERMAN: Can one just fulfill one of the four criteria and still get into the society?

DR. NEWELL: Not really. First of all, there are various points that are given. You can even be accepted if you have a master's degree and not a doctorate. But also one of the aspects required is to show a progression in your professional field over time, and also what kind of publications have you produced for the printed record, so to speak.

MS. SHERMAN: Must one do original research?

DR. NEWELL: Yes.

MS. SHERMAN: What original research have you done?

DR. NEWELL: Considerable. I have the various publications in my CV which, unfortunately, I do not have an up-to-date copy of it. I'd be glad to send it to you.

MS. SHERMAN: I'd appreciate that.

DR. NEWELL: One of the first things that appeared, I was fortunate to work with one of the outstanding scientists, biochemists at the time I was in graduate school, Conrad Elvin, who you may or may not have heard of; and subsequently, going from chairman of the department, was president of the university for a number of years.

MS. SHERMAN: I recognize seeing the name on a list.

DR. NEWELL: We did a number of studies with this running fits in dogs problem, working with wheat protein. That resulted in at least five or six peer-reviewed publications.

Did a lot of work on colon estrates inhibiting compounds, including work that was actually an NIH grant that we looked at the mechanism of colon estrates inhibition, and did patterns by injection of the compounds into the rabbits, and then taking blood samples and looking at the level of colon estrates over time. Some of the chemicals we looked at were permanent inhibitors, others were transitory and the like. That's all in the public literature.

A number of papers appeared in mutagenesis types of studies, particularly with animal reproductive studies where you're looking at the effects of a chemical causing permanent changes in the genetic structure so you get abnormalities and so forth, and the offspring, those that are dead at birth and the like.

MS. SHERMAN: Have you done any original research in the field of environmental tobacco smoke?

DR. NEWELL: No, I haven't. I might say, Ms. Sherman, the reason for that is that I've really been out of the laboratory for about 15 years. As a result, have been not in a position to do original research, as such.

MS. SHERMAN: That's why I asked you the question about the ATS. You said earlier that you had to sort of re-up this application every five years in this organization,a nd I asked if one needed to do original research, and you said yes. So it doesn't matter how long ago the original research was for membership in this organization?

DR. NEWELL: Not really, no. You're looking at what other peers have reviewed before it's published to consider whether it's worthy of appearing in the scientific literature.

MS. SHERMAN: Okay, but...

DR. NEWELL: ETS as a subject wasn't really around when I left the laboratory.

MS. SHERMAN: And you have done no original research in the field of tobacco smoke?

DR. NEWELL: No, I haven't.

MS. SHERMAN: You're not an industrial hygienist, correct?

DR. NEWELL: That's right.

MS. SHERMAN: Consultants in Toxicology, this is a company which you own?

DR. NEWELL: Consultants in Toxicology is a name I gave to my activity. It's a one-man operation.

MS. SHERMAN: I see.

How long have you been Consultants in Toxicology?

DR. NEWELL: Well, since the middle of '86 as a formal organization, although I'd been doing consulting for various clients for probably 20 years.

MS. SHERMAN: But now you do this full time?

DR. NEWELL: Well, full time as a retired person, yes.

MS. SHERMAN: You devote all of your work time to this, as opposed to all of your time.

DR. NEWELL: Right.

MS. SHERMAN: When did you first become interested in the issues relating to tobacco smoke and environmental tobacco smoke?

DR. NEWELL: I would say probably when I became aware of the developing report that EPA was going to put out on this.

MS. SHERMAN: When was that?

DR. NEWELL: Actually in the middle of '92. There was a request that came out through an Assistant Secretary of the Science Advisory Board asking for input of information from the scientific literature would be helpful. They listed various areas, and one of them was animal type studies. Because of that, and because of my concern about quality of research in the laboratory, I did an extensive review of the literature, which included looking at the foreign literature from about 1986, I believe, from that time until '92. There were a series of papers that were cited and reference and discussed.

MS. SHERMAN: Did you do this pro bono, or were you representing a client?

DR. NEWELL: I was representing a client at that time.

MS. SHERMAN: Was it a tobacco-related client?

DR. NEWELL: Yes, it was. But it was basically because of my interests and concerns about the kinds of experiments reported in the literature.

MS. SHERMAN: I believe your testimony primarily concerned the animal studies here today.

DR. NEWELL: Specifically, yes.

MS. SHERMAN: Do you believe that active smoking causes lung cancer in humans?

DR. NEWELL: I believe that smoking as such has a high risk factor for causing cancer in humans. As a causation aspect that has not been demonstrated to my satisfaction.

MS. SHERMAN: What would it take to demonstrate it to your satisfaction?

DR. NEWELL: I believe that there are various studies that need to be done, and I haven't seen them, and I really would like to get back to the issue that we have here that I came and... I want to focus on the papers that I reviewed and the comments and I'd be glad to discuss those.

MS. SHERMAN: Does the ATS have any position on tobacco smoke or environmental tobacco smoke?

DR. NEWELL: No, it doesn't. It's not a society, as such, as you might think of the Society of Toxicology or American Toxicology Society. These organizations have annual meetings, people present papers, you have symposia and so forth. ATS is an organization that recognizes people because of their contributions to the field.

MS. SHERMAN: But you're also a member of the Society of Toxicology?

DR. NEWELL: I'm a charter member, yes.

MS. SHERMAN: And do they have a position on environmental tobacco smoke or tobacco smoke?

DR. NEWELL: Not that I know of, no.

MS. SHERMAN: Do you know whether there are carcinogens present in cigarette smoke?

DR. NEWELL: There are some that have been listed.

MS. SHERMAN: Are you familiar with the literature on that subject?

DR. NEWELL: Generally speaking, although I don't believe that kind of an aspect is related to what we're talking about here.

MS. SHERMAN: In an earlier submission by WashTech, evidence was presented about animals who were exposed to environmental tobacco smoke for 90 days who exhibited reversible cellular changes in their nasal cavities and pulmonary tree. The studies reported hyperplasia. Is this effect part of the normal progression of normal cells to cancerous cells?

DR. NEWELL: Not necessarily. It's response of an irritation, and often an adaptation due to an irritation. I believe you're referring to the paper by Coggins et al that appeared in one of the SOT Journals in 1992. The authors there, if you recall, had two sets of groups. One that was sacrificed at the end of 13 weeks and then there was another group that was held for a recovery period, I forget whether it's six weeks or another 13 weeks. The hyperplasia and the like that was noted at the time when the exposure was discontinued, had completely disappeared in those animals that had been held over for a longer period of time.

Sure, it's a biological effect, but it's not a serious adverse effect. In other words, if you take the stress away that has no permanent type of effect.

MS. SHERMAN: So you feel that it was stress-related and it wasn't related to the substance to which they were exposed?

DR. NEWELL: Not necessarily. How do you define stress?

MS. SHERMAN: You're the one who just used the term.

DR. NEWELL: I didn't say so.

MS. SHERMAN: I thought you did, I'm sorry.

DR. NEWELL: No, I said that this was due to the exposure and the irritation that came from the repeated... And the hyperplasia, as I say, is reversible, so it's not a serious effect.

MS. SHERMAN: But it's possible that it can lead to a more serious effect, is it not?

DR. NEWELL: Yes, and I think you're given the opportunity there to, as you've heard from many people who have sat in my place, that the dose determines the poison. In other words...

MS. SHERMAN: Yes, I've heard that before.

DR. NEWELL: I bet you have. It comes way back from early times.

So in some cases you will get no response. In other cases, you may have an effect that goes on. I don't think you can make any judgments about the long term effects from the tissues that were found to have some metaplasia in the Coggins study. Also it's important to put on the record that there were three dosage levels. The two lower levels showed absolutely no adverse histopathology.

MS. SHERMAN: Are you familiar with the CIIT animal bioassays related to formaldehyde?

DR. NEWELL: Yes, but I don't see how they appropriately fit in with my comments here, but yes, I am.

MS. SHERMAN: Well, it seems to me that in those cases you had hyperplasia and metaplasia that did progress to more serious changes.

DR. NEWELL: That's not true completely. Some of them did at the highest level, 15 parts per million, but at the lowest level, five parts per million, which incidentally, other people have been exposed to that. You and I couldn't stand that environment for even a minute or two, it is so irritating to humans. Yet rats lived in there for their lifetime and all they showed was a little bit of hyperplasia, but nothing progressed further in that lower dosage group.

MS. SHERMAN: Might that not be because there weren't all that many rats in each group?

DR. NEWELL: I don't know how many... They had something like 50 males and 50 females in each group. It was a large number. It certainly met the standards of the ETP design.

MS. SHERMAN: Do you disagree with general toxicological protocols where you expose animals to relatively high doses in experiment design?

DR. NEWELL: I know what you're leading to, and that certainly is the approach and the defense of that position as you well, I'm sure, have heard is that well, we've got to make sure that we don't overlook something, so let's does animals at the maximum. Essentially the maximum tolerated dose.

I don't have too much trouble with that as long as we have several different doses. You can see if there is a dose response or not. There are many studies in the literature today which will show, in effect, the very highest level. Generally there is an attempt to try, on these long term studies, to assure that an experiment causes no more than a 15 percent of death just because of the toxicity of the chemical.

MS. SHERMAN: At any dose level?

DR. NEWELL: Pardon?

MS. SHERMAN: At any dose level.

DR. NEWELL: That essentially is the maximum tolerated dose backed off a bit so that you have a sufficient number of animals that can go through the experiment.

But what I'm saying is, it's important, just because you get something at that highest level dose, very frequently you see nothing, particularly with non-genotoxic type of chemicals. You do get, particularly you get the irritation, and I'm sure people have cited the work that Bruce Ames has published on in the literature in this relationship. And others, the University of Nebraska has also published the same kind of work.

MS. SHERMAN: If you only have 100 animals in each test group -- 50 males and 50 females -- and you see statistically significant effects in the top two dose levels, do you think that allows you to conclude that there is no effect in the lower dose level?

DR. NEWELL: Certainly that's on the basis which I have to go with the information that's available to you. Sure, it would be desirable if you had 1000 animals per dose level, and that kind of thing was done at NCTR years ago.

MS. SHERMAN: However, that's rarely done, right?

DR. NEWELL: The mega-mouse study. And it ended up with more complications than people have still been able to well sort out and sift out.

MS. SHERMAN: So it's not common to have animal cohorts where you have say 5,000 animals at any particular dose level. It's not practical.

DR. NEWELL: It's not cost effective. People can't afford to handle that sort of large numbers. I know of no study other than the NCTR mega-mouse study that approached anything like that.

MS. SHERMAN: So we make certain assumptions about the shape of a curve based on relatively small sample sizes, and a limited number of dosing regimens.

DR. NEWELL: I would say a small sample size is when you try to draw conclusions from five or six animals in a test group. I think when you get up to 50 or 100 animals, or 70 animals per dose level, you're getting a realistic response. Remember, animals are in-bread, hopefully, to minimize a lot of variations. That's not always true, unfortunately, but still it's a lot better than getting random animals off the street or out of the woods, as some people go for.

MS. SHERMAN: Clearly.

However, if the effect that one thinks one will see would translate into say a risk of three per thousand, and one only has 50 animals in a dosing group, the effect may be there and it may not be seen, wouldn't you agree?

DR. NEWELL: It's very possible, certainly, but that's part of the risk of doing research. As I come back to you, you said as you get the effects that you might expect to see.

If you're looking at new material, you're looking to see whether or not there is any effect, not that you're there to try to make sure that that particular effect occurs. There's a difference in objectivity in the design of the experiment. That's all I'm trying to emphasize.

MS. SHERMAN: Perhaps you misunderstood what I was saying. I understand that sometimes there is other data that makes one think that you're going to see an effect, and then an animal bioassay may be done to further investigate a hypothesis, perhaps.

DR. NEWELL: And to quantify the results.

MS. SHERMAN: This is acceptable science, is it not?

DR. NEWELL: Sure. That's one of the reasons you do the shorter term studies, like the three month studies, and they give you parameters on which you can then frame a larger, longer term experiment.

MS. SHERMAN: On page two of your submission, I think you criticized the Moore and Resnick study titled "Biological Tests for Tumorigenic and Cilia Toxic Activity." I think you indicated that changes of hyperplasia and metaplasia in the trachea and bronchi of mice exposed for long periods to tobacco smoke, was relatively minor. Is that correct?

DR. NEWELL: Yes. That's what the author said.

MS. SHERMAN: And you agreed with this?

DR. NEWELL: All you can do is take what was in the literature, and I'm just lifting out the comments they had.

If you go on you can see the remainder of the comments. The authors continue that, "In the absence of infection, no significant pathological lesions were noted in the trachea, main or small bronchi, or the bronchioles, even after exposing mice more than 300 times for 15 minutes each time to cigarette smoke."

MS. SHERMAN: How many cigarettes are there in a pack of cigarettes?

DR. NEWELL: I'm not a cigarette smoker. I believe I've been told it's 20, but I'm not a...

MS. SHERMAN: I believe that's correct. I'm told that.

Do you know how long it would take a one pack a day smoker to smoke 300 cigarettes?

DR. NEWELL: Not really. I think it all depends on how rapid a person is going to smoke, There are all sorts of variables that could be involved with that. I don't feel I could comment on that in a meaningful way.

MS. SHERMAN: The simple mathematics is that if one consumes one pack a day, that's 20 cigarettes a day...

DR. NEWELL: Some people consume three packs a day.

MS. SHERMAN: But my question was, how long would it take a one pack a day smoker to consume 300 cigarettes. So it would seem to me that what one would do would be, one would divide...

DR. NEWELL: It would be like two months.

MS. SHERMAN: ...20 into 300.

DR. NEWELL: Yes.

MS. SHERMAN: I think you'd come out with 15 days.

DR. NEWELL: Yeah.

MS. SHERMAN: Do you know how long it takes to smoke a cigarette? Is that where your variables come in?

DR. NEWELL: No, except that there are certain smoking machines that are used supposed in an attempt to simulate what humans do. I've not had direct experience with those, but there are test procedures that seem to have been acceptable to everyone that works in the field of tobacco smoke.

MS. SHERMAN: Would you think that probably 10 to 15 minutes would be an appropriate amount of time to smoke a cigarette?

DR. NEWELL: I don't know. That's far afield. I don't quite see how that relates to my exposures here with the rats and mice.

MS. SHERMAN: I guess what I'm getting to is, in the study you just quoted, I believe that you said that "In the absence of infection, no significant pathological lesions were noted in the trachea, main or small bronchi, or bronchioli, even after exposing mice more than 300 times for 15 minutes, each time to cigarette smoke." That's just what you read, correct?

DR. NEWELL: Right. And that's a quotation from the article. It's not my words. The authors wrote that.

MS. SHERMAN: Given that it would take a typical smoker 15 days, this is a typical, one pack a day smoker, to be exposed to cigarette smoke, 300 times for 15 minutes each time, would you believe that the absence of an effect in the study you quoted is definitive proof that smoking doesn't cause lung cancer?

DR. NEWELL: This is another experiment that did not show any response in terms of producing tumors in these animals.

MS. SHERMAN: I guess what I'm trying to say is, wouldn't you agree that the amount to which the animals was exposed was not a very large amount in the whole scheme of things. So how...

DR. NEWELL: No, I can't say I would agree with that, because I don't know what the relative time, what was available to me here, and the volume... Sure, they had to smoke a cigarette and so forth, but it was a long and repeated exposure that those animals had.

MS. SHERMAN: I guess we've heard a lot from scientists claiming that the animals were dosed at too high a level, and therefore, any results have to be discounted. This appears that perhaps the animals were dosed at too low a level.

DR. NEWELL: I'm not sure they were dosed at too low a level. All you can do is take what's required in the literature and the kind of results that are obtained. That's a judgment, I think, that you're making that it's at too low a level. I don't know whether that's true or not.

JUDGE VITTONE: Did you finish your question? I don't think you finished your question.

MS. SHERMAN: I probably didn't, but I may have lost it.

With reference to the same study, if we were to move to the workplace, do you believe that there are workers in the United States who are exposed to cigarette smoke more than 300 times for 15 minutes each time in the course of their work?

DR. NEWELL: I really don't know, and I feel that that's not necessarily appropriate to the animal studies. You're now moving over to occupational environments and the like and you'd like to try to apply that, but you're asking me for an opinion on something I don't feel I'm basically qualified to answer.

MS. SHERMAN: Except the reason one looks at animals studies is for whatever relevance they have to the agency's task at hand, which, of course, is helping to assure the health of American workers. So one has to assume that there has to be some relationship or else one wouldn't look at animal studies at all.

I guess what I'm saying is, I know in toxicity studies you have different concerns about scaling factors, et cetera, et cetera. However, without even worrying about scaling, do you think that American workers might be exposed to smoke for 15 minutes, 300 times during their working lifetimes, or perhaps more than that?

DR. NEWELL: Under what circumstances, that's always a possibility, but what we've been able to see, if you want to try to take a translation from the animals cited by OSHA, does not justify it as saying you can transfer that over because there's really not a significant adverse long term health effect in these studies.

MS. SHERMAN: No, but might it not be possible to say that the exposures in this study were perhaps very short compared with realistic exposures that might be experienced by real workers?

DR. NEWELL: Lifetime exposures are short, or six year studies with dogs are short? No, I don't think so. Bioassays of two years duration are considered as long term exposure.

MS. SHERMAN: However, this was not that exposure, correct?

DR. NEWELL: I'd have to go back and look at the protocol, because it says they had done it 300 times for 15 minutes each, but I don't know what frequency that was. Was that daily or was it every other day or just what? You'd have to go back and do it. My feeling is that 300 times is a rather extensive and long period. It would be interesting, actually, to know what the survival rate of those animals were. That wasn't available to me.

MS. SHERMAN: You think that they may have maxed out?

DR. NEWELL: There are all sorts of reasons why animals don't survive. Many times it's just poor housing and handling conditions and they get infections unrelated to the test organization.

MS. SHERMAN: Dr. Gio Batta Gori appeared here earlier this month, and he also has submitted some comments to the docket. Are you familiar with his work?

DR. NEWELL: Generally. I'm more impressed with him as a scientist in terms of his knowledge and the like of specific positions. I haven't read all of his papers, no.

MS. SHERMAN: In a status report in 1978, Dr. Gori stated that the major toxic agents present in the gas phase were shown, and that several of these chemicals were cilia toxins which impaired the clearance of foreign particles from the lung.

And that interference with this function is especially dangerous, since it can result in the accumulation of toxic and carcinogenic agents, enhancing the disposition of respiratory disease.

Do you consider cilia toxicity to be an adverse health effect?

DR. NEWELL: It's a biological effect, and yes, it can be a toxic effect. But it's also, in many cases, been shown to be reversible. You take the stress away. And I think also it's appropriate to mention that Gio was discussing there direct tobacco smoke exposure, not ETS, which is why we're here.

So I think I'd like to see some studies done of the ETS and do they affect the cilia.

MS. SHERMAN: I was just going to ask you, do you know the cilia toxicity, I think it's called a NOAEL, no observed effect level, for any of the ETS chemicals which Dr. Gori termed to be cilia toxins such as nitrogen oxide, or hydrogen cyanide?

DR. NEWELL: I'm not privy to that. I'm sure there are paper in the literature that present that information.

MS. SHERMAN: Would you expect a mixture of cilia toxins to be additive or synergistic or antagonistic?

DR. NEWELL: That's an interesting question that you raise. One of the difficulties in trying to assess the hazards of low concentrations of materials has always been a problem. A problem trying to address it.

The National Academy of Sciences had a request from the Coast Guard some years ago to look at the potential toxicity of vapor residues that were in the tanks of their cargo ships where their inspectors have to go down and look at things, and there were small residues. The committee that was assigned the task to come up with that question, as to what is the potential hazard, at that time, which was about 15 years ago now, threw up its hands because there was nothing in the literature that said you could reliably expect it to be an additive or negative or a compensating...

Actually there wa a further study that's been done on this general subject, it was either by EPA, a subcommittee of the Science Advisory Board, or another NAS group. They said we don't have any basis for it, but we're going to make an assumption that these very low concentrations are additive, but there's no justification for that that you can really count on. In many cases, you're going to find one chemical can neutralize the other one in terms of its effect, or may even be potentiating. It's a very difficult issue. It's one that I've been interested in, but I've just thrown up my hands over time, because it's almost impossible to get the information.

MS. SHERMAN: Do you have any opinion as to under what circumstances cilia toxins would have an antagonistic effect?

DR. NEWELL: Not really. I think you've got to go in and do the study. I think it should be done, if you're going to do it. Maybe OSHA would like to look at that, as to who would do it with environmental tobacco smoke, as we understand it by definition.

MS. SHERMAN: There's not a well developed literature on this subject?

DR. NEWELL: I don't know, because I'm not an expert in that.

MS. SHERMAN: Dr. Gori also stated in a record submission that carbon monoxide was a major toxin present in cigarette smoke, and it caused damage to the cardiovascular system, as well as other physiological functions. Do you believe that carbon monoxide causes damage to the cardiovascular system?

DR. NEWELL: As it may appear in environmental tobacco smoke? That's what we're here on.

MS. SHERMAN: Yes.

DR. NEWELL: I would say from what I've listened to, particularly other people, the concentrations are so low, I'd say no.

MS. SHERMAN: Do you know the safe level below which carbon monoxide does not produce damage to the...

DR. NEWELL: I couldn't give you a figure off the top of my head. That would be an act of pulling a number out of the sky. I really think you've got to go back and see what the general literature is on it. I don't have a figure on that, no.

MS. SHERMAN: If you have some second thoughts about that, if you'd like to put them in a post-hearing comment, I'd appreciate it.

DR. NEWELL: This is what you want... Would you repeat again what it is you want?

MS. SHERMAN: The safe level below which carbon monoxide does not produce damage to the cardiovascular system.

DR. NEWELL: Okay.

(Pause)

DR. NEWELL: I'll be happy to address the issue and give you an answer. It may be difficult, but nevertheless.

MS. SHERMAN: Excuse me?

DR. NEWELL: I said I'd be happy to address the issue. Whether I can give you the kind of answer you ask for is...

MS. SHERMAN: It may not be discernible.

DR. NEWELL: That's what I'm saying.

MS. SHERMAN: We've had some comments at this proceeding along the lines that no health effect should be expected from a mixture as long as each individual chemical is at or below the permissible exposure limit. Would you agree with these sentiments?

DR. NEWELL: Would you repeat that again?

MS. SHERMAN: We've been talking about mixtures and antagonisms, et cetera.

DR. NEWELL: Yes.

MS. SHERMAN: Some people who have submitted comments to the record have opined that one should not expect to see any adverse health effects from a mixture as long as each chemical in the mixture is at or below the permissible exposure level. Would you agree with this?

DR. NEWELL: Yes, I would, on the basis that you're looking at, particularly if we're coming back to ETS, which is why we're here, very, very low levels. And listening to some of your witnesses in the last several days, they've pointed out that the amounts of these various chemicals that are found in ETS are far below what is considered as an acceptable PEL for them. There seems to be a discrepancy there.

Again, we can't really take and say these things are additive or inhibitory. All the possibilities exist. That's one of the problems with mixtures -- it's a variable.

MS. SHERMAN: In other words, while you can't say that, you also can't rule it out because we just don't know.

DR. NEWELL: That's right, and that's a proper position to take. If you don't know, it's wrong to take a position just because you feel that way.

JUDGE VITTONE: Ms. Sherman. Would it be okay to take a short break right now?

MS. SHERMAN: I think I'd like that, Your Honor.

JUDGE VITTONE: Ten minuets.

JUDGE VITTONE: On the record.

Ms. Sherman?

MS. SHERMAN: I think in your review of the study by Davis et al, your main criticism were that the rates were exposed to cigarette smoke condensate by intra-tracheal installation. Is that correct?

DR. NEWELL: What page are you on? Was this in part of my submission?

MS. SHERMAN: I believe so.

DR. NEWELL: Yeah, I think it's Exhibit 479, isn't it?

MS. SHERMAN: Yes.

DR. NEWELL: Yes.

MS. SHERMAN: That was one of your main criticisms?

DR. NEWELL: Yes, I think basically, first of all it was certainly not related to ETS as what we're looking at here. It was certainly not a smoking study because they took cigarette condensate and applied that to the intra-tracheal area.

MS. SHERMAN: So you think that the root of exposure is of critical importance?

DR. NEWELL: Very much so.

MS. SHERMAN: Why is that?

DR. NEWELL: That's the realistic way people get exposed to particular material you're looking at. I think the most critical aspect in that regard is you can cause tumors, as you probably well know, with almost anything if you put it in inert material into the muscle area of an animal. Over time, that irritation will cause tumors. So it's non-specific. And it doesn't mean anything. You'll find citations in the literature saying this thing is a tumorigen, but it was done when the material was implanted intermuscularly. So in fact, the item that I put up on the overhead indicated one of the important criteria that NTP uses, to use the root of exposure which is the manner in which you're most likely to run into this material or have exposure to it.

MS. SHERMAN: So you would disagree with any study that showed a toxic effect, say by intubation when you thought the root of exposure might be inhalation?

DR. NEWELL: Yes, because very oftentimes those kinds of tests are not at all related to dosage. If you were going to have an inhalation study and then you put the material in like a beeswax and put it in the intra-tracheal area and see what happens there, that is not the same way. I mean, sure, you can do any sort of thing you want, but it's not meaningful. It doesn't relate to the real life that you're hopefully trying to simulate.

MS. SHERMAN: Getting back to the Davis study which used cigarette smoke condensate, how is cigarette smoke condensate generated?

DR. NEWELL: I'm not an expert in that area. All I can tell you is it's concentrated. Then as they say, the put it in an inert medium so that it will stay in the area of the body over an extended period.

MS. SHERMAN: Does it contain all the components of the particulate phase and gaseous phase of cigarette smoke?

DR. NEWELL: I really don't know. As I told you, I have not done any work specifically with either primary tobacco smoke, mainstream or sidestream.

MS. SHERMAN: What is a pre-neoplastic change?

DR. NEWELL: It can well be in an area that could lead but not necessarily, could lead to malignancy. Again, you have to... Well, that's enough.

MS. SHERMAN: So in your review of the Dalby et al study, when you indicated that authors comment that squamous nodules were observed in nine percent of the smoke-exposed animals, and may represent pre-neoplastic changes, what you mean by that is that these changes may lead to neoplasia?

DR. NEWELL: Possibly, but also you note that the authors do not claim that they developed any lung cancer in these animals.

MS. SHERMAN: Do we know all the conditions...

DR. NEWELL: Even though that was after two and a half years of exposure.

MS. SHERMAN: Do we know all the conditions under which pre-neoplastic changes will lead to neoplasia?

DR. NEWELL: I don't think so. Again, this was direct cigarette smoke exposure, not an ETS study.

MS. SHERMAN: Excuse me?

DR. NEWELL: This was exposure of animals to cigarette smoke directly, rather than an ETS type of study. One of my main criticisms of the OSHA submissions is they don't relate to the issue trying to be addressed.

MS. SHERMAN: So these animals were smoking animals?

DR. NEWELL: Yes. Smoke-exposed, yes.

MS. SHERMAN: They were exposed to smoke or they smoked?

DR. NEWELL: I'm quoting from what is written here. It says, "also mortality of smoke-exposed animals was not different from the untreated sham-exposed," so actually...

MS. SHERMAN: I didn't hear you, I'm sorry.

DR. NEWELL: There's no difference in the mortality between those animals that are exposed to cigarette smoke and those that were the sham-exposed, that were unexposed.

MS. SHERMAN: So this is not necessarily an issue of active smoking versus ETS.

DR. NEWELL: No, not at all. I'm saying that with active smoking, in this particular situation, did not have any effect on mortality of the exposed animals related to the unexposed.

MS. SHERMAN: I think you criticized the study by Auerbach and Hammond as controversial?

DR. NEWELL: It's well known in the literature.

MS. SHERMAN: And you stated that "the design and interpretation of this investigation has been severely criticized by many investigators. Also, the manuscript was previously submitted to another journal and was rejected after its examination by 12 reviewers." Is this correct?

DR. NEWELL: There's a citation in the literature. I didn't give you a citation on that, but there is a letter to an editor in one of the journals that refers to that specific aspect.

MS. SHERMAN: That's where you got your information?

DR. NEWELL: Yes.

MS. SHERMAN: So you wouldn't know the investigators who criticized it?

DR. NEWELL: No, I don't.

MS. SHERMAN: Aren't all submissions to peer-reviewed journals supposed to be confidential?

DR. NEWELL: Supposedly, but often that gets taken out of context and particularly if there's a subject where authors are in a very hot research area, you'll find that the word gets around.

The literature is full of claims of someone upstaged them and got their manuscript accepted and published before the other guy because the confidence was not maintained.

MS. SHERMAN: Is it normal for a journal to assign 12 reviewers to one article?

DR. NEWELL: I don't really know. As I told you, I reviewed numerous manuscripts over time...

MS. SHERMAN: That's why I'm asking you.

DR. NEWELL: ...and I never have known how many people. The editor has his own reason to send out a manuscript to maybe one or maybe six people, it all depends on how important, questionable, controversial, the subject matter might be.

So I have no idea how many people, I'm sure that there's more than one, but I certainly have no idea how many people are asked to look at the same manuscript that I've looked at.

MS. SHERMAN: You also have been in the position of submitting manuscripts to peer review journals, have you not?

DR. NEWELL: Certainly.

MS. SHERMAN: When you get the feedback from the peer reviewers, is there any way you can tell how many people are giving you feedback?

DR. NEWELL: It depends on the practice of the journal. In some cases the comments of a reviewer will appear in a paragraph, and they'll say this reviewer one, two, and three and so forth; other times there's just a whole grouping of comments together. No, it's not possible to... Certainly, I've never found out who was reviewing my manuscripts.

MS. SHERMAN: I wasn't really referring to how, I was referring to how many.

DR. NEWELL: It's an individual choice of the editor.

MS. SHERMAN: Did you say that you hadn't supplied us with the reference for this? I think you said this information came from a letter to the editor of one of these journals?

DR. NEWELL: I have the letter out of a journal. I didn't abstract it. I can get it for you.

MS. SHERMAN: I would appreciate it if you would submit that.

DR. NEWELL: Sure.

MS. SHERMAN: Again on this Auerbach and Hammond study, your criticism involves the method of exposure, the tracheostomy?

DR. NEWELL: No. I think you'll find in almost all of the dog studies that are in the literature, our tracheotomized beagles, actually the beagle has been the species that has been used. And of course the reason for using that kind of an approach is to get around the criticism, well these animals are nose breathers, and therefore they're filtering out a good share of the material. So by using a tracheotomized dog when you put a tube down, they can get the smoke directly going down the trachea and into the lungs.

MS. SHERMAN: So you feel this is an acceptable procedure, or you don't?

DR. NEWELL: I think it increases the opportunity for the material being studied to get into the lungs. It creates problems of stress on the animals. It creates potential infection problems. In fact that was one of the difficulties with the Auerbach study, it's noted that there was an extensive amount of infection in the dogs at the time the first study was terminated.

MS. SHERMAN: So is this acceptable to you? Would you just reject the tracheostomy studies or do you think they're...

DR. NEWELL: If they're well done and the like, I think that's an additional way to maximize the exposure.

MS. SHERMAN: Also in the Auerbach and the Hammond study, you seem to be advancing a theory about lung worms?

DR. NEWELL: There's no theory. The histology looked at both the tissues they were able... My understanding is that the reviewer was able to get copies of the slides that Auerbach had from his dogs, and compared them with the histopathology that he saw in his dogs. They both came from the same breeder in Michigan, and they both had the nature of lung worms present.

MS. SHERMAN: Do you have the slide of the results that you could submit?

DR. NEWELL: Do I have which?

MS. SHERMAN: Do you have a slide of the histopathology results of that?

DR. NEWELL: I'm not a histopathologist. I wouldn't be able to even interpret the things if I had it.

MS. SHERMAN: What are some of the symptoms of lung worm infestation?

DR. NEWELL: They're a complication, I understand. I really don't know. But the point was, here was a pathologist looking at the tissues, and he said look, these are similar to what Auerbach had in his dogs, and both of those dogs came from, I forget the breeder. I've been to their labs in Michigan. They have had numerous problems with their beagles.

MS. SHERMAN: So it was not just one litter of beagles, it was all litters?

DR. NEWELL: I don't know. First of all, a breeder is never going to admit he has that kind of a problem. It only occurs as a result of experience and distribution of the animals.

MS. SHERMAN: Is there any way that a cautious researcher can test the animals before he starts, before he invests a lot of time ad money in the experiment?

DR. NEWELL: Lung worms is very difficult, unless you want to take and sacrifice some of the animals, and when you're paying today upwards of $500 to $750 a dog, it's very unlikely you're going to sacrifice two to three of those to make sure that they're lung worm free.

MS. SHERMAN: Five hundred dollars a dog?

DR. NEWELL: You bet. Some cost $1,000.

MS. SHERMAN: Perhaps I'm in the wrong business.

DR. NEWELL: Well...

MS. SHERMAN: Have you read the study by Zhu et al?

DR. NEWELL: I think I referenced it, did I not?

MS. SHERMAN: I believe you did.

(Pause)

DR. NEWELL: Can you lead me to it?

MS. SHERMAN: I think you testified to that this morning. You talked about cardiovascular effect, and I assumed you were talking about the Zhu study.

DR. NEWELL: I don't believe so. Wasn't I talking about a dog study? And having no effect.

MS. SHERMAN: Have you read the Zhu study? This is the one about the environmental tobacco smoke in the rabbits.

DR. NEWELL: If I don't have it available, I don't feel comfortable in commenting on it. You say I referenced...

MS. SHERMAN: You talked about cardiovascular effects in animals.

DR. NEWELL: That's true, but that was in a dog study. The inhalation study with beagles was done at Hazelton Labs.

MS. SHERMAN: We've had a lot of discussion here this morning about the way the animals are dosed, et cetera, so I thought you might find the Zhu study more acceptable to discuss since the animals were exposed to environmental tobacco smoke.

DR. NEWELL: Are you sure that's C-H-U?

MS. SHERMAN: Z-H-U.

(Pause)

MS. SHERMAN: Did you do a literature search on cardiovascular effect to come up with the studies you discussed?

DR. NEWELL: No, I didn't. The study I just mentioned here, the cardiovascular, was a fall-out on the basis of smoking inhalation studies that were done with dogs, and it just so happened that the emphasis, it was an NCI-supported study. A terrible study in terms of design. I'd be embarrassed. It was high fat, high cholesterol, and on top of that, they used tracheotomized dogs and gave them supplements of carbon monoxide and high and low nicotine containing cigarettes. I think it's just terrible. And you expect to get meaning types of results out of that?

It just so happens that if anything, the comment was it looked as though some of the smoking dogs had a protection against any effects in the cardiovascular system. That was noted by the authors.

MS. SHERMAN: Did you read our Preamble discussion of cardiovascular effects?

DR. NEWELL: No, I didn't. I focused merely on the animal studies related to potential carcinogenicity.

MS. SHERMAN: In our discussion here this morning, you've pointed out the distinction between active smoking and passive smoking several times. What is the difference in chemical composition between environmental tobacco smoke and mainstream smoke?

DR. NEWELL: I can't give you as I sit here a quantitative summarization of it. I wouldn't be able to because there's, according to what's in the literature, many more identified compounds that come out of mainstream smoke and a lesser number out of sidestream, as I understand it. Not a much lesser number, but a somewhat similar composition, but of different composition than what is considered environmental tobacco smoke. So I'm not quite sure what your question is.

MS. SHERMAN: What are some of the troublesome constituents in mainstream smoke that are absent in environmental tobacco smoke?

DR. NEWELL: I'd have to go back and give you something in writing on that. I think that's a question I can't answer to you. I can't say I can give you a list of all the different compounds that are present in ETS versus mainstream or sidestream.

MS. SHERMAN: Wouldn't you agree that some of the constituents in mainstream smoke that have been identified as being carcinogens are also present in environmental tobacco smoke?

DR. NEWELL: According to what's bene published in the literature, yes. Some are. But again, the dose determines the effect.

MS. SHERMAN: Do you know of studies that show a safe threshold level for these carcinogens?

DR. NEWELL: I can't quote them to you, though I know with certain of the chemicals, indeed that has been put into the literature.

MS. SHERMAN: If you happen to have that at your disposal I'd be interested in your opinion on it.

DR. NEWELL: May I rephrase your question by saying, can you provide us with threshold data of no effect of some of these purported carcinogens for animals?

MS. SHERMAN: Certainly.

DR. NEWELL: That's what you're asking for.

MS. SHERMAN: Earlier in this hearing, Professor Jeffrey Idle testified, and he also submitted a written comment in which he said that cotinine is not the principal metabolite of nicotine, but it's, rather, an intermediate.

As a toxicologist, could you explain the difference between a metabolite and an intermediate?

DR. NEWELL: I think the designation of a metabolite is pretty well established in the literature in that it, you start with an original compound and under the influence of whether it's enzymes or various body fluids, the chemical nature, the nature of the chemicals, the structure of the compound changes. While an intermediate, and again, I'm not quite sure exactly what this man means, but an intermediate means just what an intermediate means. It's halfway through or partway through a process. He's implying that, I don't know his testimony, I don't even know the gentleman you're referring to, but he's implying that there is another change which cotinine would go through before the final structure.

I'm not an expert in that area, so I can't....

MS. SHERMAN: So you don't have any basis of agreeing or disagreeing with them?

DR. NEWELL: No. He made a statement. I don't know if it's true or not. Did he have any data to back it up?

MS. SHERMAN: Well, I don't what to characterize his testimony before I've analyzed it.

Professor Idle also stated that it's incorrect to imply that the rat is a good model for man with respect to nicotine metabolism and disposition. Would you agree with that statement?

DR. NEWELL: I don't know enough about nicotine. I haven't really studied it. I wouldn't venture an opinion on it because it's not an area that I've studied.

MS. SHERMAN: Are you familiar with what the professional opinion is in this area? In other words, do you think that professionals in this field feel that the rat is or is not a good model to study nicotine metabolism? Have you read the literature on it?

DR. NEWELL: No, I haven't. Is there a criticism about it? You're implying that there is. I'm not in a position to make an informed judgment.

MS. SHERMAN: Professor Idle also testified that there can be no good animal model for human environmental tobacco smoke exposure. Do you agree with him?

DR. NEWELL: No, I don't. That's a very broad, absolute statement. Maybe we ought to use the ferret that has a long trachea and so forth, would be useful. I think that's an absolute type of position that's insupportable.

MS. SHERMAN: Are you familiar with any research done with ferrets on this subject?

DR. NEWELL: No, not on this subject, but the ferret is a well-used study test animal; particularly, my friend at U.C. Irvine has used it in air pollution studies.

MS. SHERMAN: I think you also stated in your written comments that it's recognized that non-human primates represent a valuable model for predicting human carcinogenic risk due to their close philogenic relationship to humans, low spontaneous tumor rate, relative longevity, and large organ size. Is that correct?

DR. NEWELL: That's not only just my comment, but that's pretty well generally accepted in the scientific community.

MS. SHERMAN: Do you believe that the non-human primate is a better animal model than rats to study the environmental tobacco smoke induced carcinogenesis?

DR. NEWELL: It might be, but it's very difficult to be able to afford to carry out studies of a significant size to get statistical significance using the non-human primate.

MS. SHERMAN: Do you know anything about the metabolism of nicotine in non-human primates?

DR. NEWELL: No, I haven't studied that.

MS. SHERMAN: So you don't know whether it's similar to humans or not?

DR. NEWELL: No, I don't.

MS. SHERMAN: There has been a lot of discussion in the record about the advisability of OSHA setting a permissible exposure limit for environmental tobacco smoke. As a toxicologist, would you have any advice to OSHA as to how they should set one?

DR. NEWELL: It would be presumptuous on my part to give you advice. I believe I would recommend to you and to ask get in touch with the people at the National Toxicology Program, Dr. Richard Griesemer, currently of the NTP, and Dick would be more than happy to provide you guidance and advice. They carry out inhalation studies or they support inhalation studies on a regular basis.

MS. SHERMAN: I believe that you submitted many documents to us in response to our request for information in 1992?

DR. NEWELL: Yes. That was a review of the literature on animal studies, as available at that time.

MS. SHERMAN: Well, I'm more interested now in the submissions you made to the record on Legionella. Do you remember them?

DR. NEWELL: Not specifically, but go ahead.

MS. SHERMAN: Well, I was going to ask you a series of questions concerning the mitigation of Legionella contamination of water systems and something about the disease.

This Legionella bacteria occurs naturally in water. Do you know under what conditions it becomes a problem?

DR. NEWELL: Yes and no. In my experience, we at EPRI supported some work and followed up on some work that was done in Canada on this. One of the rather acute areas and problems are on the back side of the showerheads, and actually the organism tends to be able to grow there.

Also, in the water tank, the heating tank, in homes, would be a source of contamination also, and that is difficult to control, but if you change the structure of the tank itself, you can minimize those sorts of problems. Those are probably my main contribution to that. There's been a lot of work done by people at the Department of Public Works, the City of Philadelphia, which if you and OSHA have not contacted, I would recommend them to you.

MS. SHERMAN: Well, are you familiar with any of the literature linking Legionella outbreaks to modern HVAC systems which allow it to develop and proliferate?

DR. NEWELL: I haven't really read the literature so I don't think I could make a meaningful comment on that.

MS. SHERMAN: Do you know whether certain groups of people are more susceptible to Legionella infection than others?

DR. NEWELL: No, I really don't. Interesting question.

MS. SHERMAN: Do you know if there's an optimum temperature for a Legionella growth?

DR. NEWELL: Now you're getting into technical aspects, and I really wasn't -- I know that it's difficult to culture the presence of Legionella, and what I was told by an investigator in Canada, that you had to have a minimum number of organisms per cc, otherwise you wouldn't get results that you could count on, even though the organisms were present.

MS. SHERMAN: And sometimes even when you have them, you don't get results, apparently.

DR. NEWELL: That's what I'm saying.

MS. SHERMAN: Have you had an opportunity to read the OSHA proposed regulation on indoor air quality?

DR. NEWELL: Not completely. I focused pretty much on the area that we talked about here concerned with the animals. You know, the problem of bacteria and the like of Legionella is part of the issue that OSHA feels needs to be addressed.

MS. SHERMAN: Do you think that the requirement in the proposal to maintain water treatment logs and to include information on potable hot water storage and delivery temperature in a compliance plan would reduce Legionella concentrations in both the potable and HVAC-related waters? DR. NEWELL: I just don't feel I'm much of an expert on that. I know it's difficult to get people to continually fill out forms they're asked to fill out.

MS. SHERMAN: Thank you very much for your time, Dr. Newell.

DR. NEWELL: Thank you.

JUDGE VITTONE: Thank you, Ms. Sherman.

Let me have a demonstration of who has questions.

(Responses.)

Mr. Weinberg. Okay. Give me an estimate.

MR. WEINBERG: 20 to 30 minutes.

JUDGE VITTONE: 20 to 30.

Mr. Andrade.

MR. ANDRADE: About the same, Your Honor.

JUDGE VITTONE: 20 to 30.

VOICE: 10.

VOICE: 20.

JUDGE VITTONE: What would everybody like to do? Would you like to go ahead and try to finish? It seems to me it's going to take us maybe an hour, maybe a little bit more. Would you like to go forward for a little bit and then break for lunch or break for lunch now? What would be your preference?

DR. NEWELL: I would like to go through it and get it over.

JUDGE VITTONE: You would prefer to go through it and get it over with. Okay. Anybody have a problem with that?

(No response)

JUDGE VITTONE: Okay.

Who wants to go first? Go ahead.

I will plan to break about 12:30, just to take another short recess.

MR. KLOK: Good afternoon, Mr. Newell. My name is Rhett Klok, and I'm here on behalf of Docket No. 24 and 10, and I work for Sibley law firm.

I would also like to make it clear for the record that my firm is involved in the Costano tobacco litigation and are members of the PLC Committee.

Mr. Newell -- and I'm not sure if I listened correctly -- you stated the name of your organization, of which you are the sole member, named, Consultants in Toxicology. Is that correct?

DR. NEWELL: That's correct.

MR. KLOK: Are there any other members, besides yourself, in that organization?

DR. NEWELL: I stated that I was the only member.

MR. KLOK: Is there any particular reason why you called it Consultants?

DR. NEWELL: Sure. I thought it was an appropriate name.

MR. KLOK: Okay. I was just curious.

DR. NEWELL: I thought somebody would raise that.

MR. KLOK: Yes. You stated earlier that you have over 80 scientific papers that you published; is that correct?

DR. NEWELL: That's correct.

MR. KLOK: Did you provide your c.v. to the record?

DR. NEWELL: I will. I don't have an update one. That will be sent.

MR. KLOK: Could you please provide a list of those publications?

DR. NEWELL: It's in the c.v.

MR. KLOK: Okay. Thank you.

Out of those publications, how many have been published since 1988?

DR. NEWELL: Peer reviewed, I don't know. I mean, you're asking --

MR. KLOK: Ball park.

DR. NEWELL: -- a question --

MR. KLOK: Ball park.

DR. NEWELL: Peer reviewed papers, probably very few because, as I stated to someone here, I've been out of the laboratory for 15 years, and you don't get a chance to develop new information. You make written reviews and commentaries and so forth.

MR. KLOK: Have any of those papers been co-authored?

DR. NEWELL: I don't know. I'd have to go back and look what's in the CV.

MR. KLOK: You don't remember if any of them have been co-authored?

DR. NEWELL: No, I don't, at the moment. Probably not. The later ones.

MR. KLOK: How many of those have been authored in the name of your Consultants in Toxicology group?

DR. NEWELL: Not really. They've been under my personal name.

MR. KLOK: Have any of these studies been sponsored, financed, by the tobacco industry, agents, or trade organizations?

DR. NEWELL: I really don't know at the present time. You're asking me questions in detail that is not appropriate for me to try to address when I don't have it in front of me.

MR. KLOK: You mean to tell me you don't remember any, correct?

DR. NEWELL: I don't, at the present time.

MR. KLOK: Okay. In preparation for the hearings, have you spoken to any lawyers, particularly any lawyers associated with Philip Morris?

DR. NEWELL: Sir, the way I conduct my business, I consider it a private and confidential, and I've stated for the record here that I have appeared on behalf of Philip Morris, and that's as far as I plan to go.

And, Your Honor, I have nothing further to say on that subject.

MR. KLOK: Your Honor, I think it's important for the record, since there seems to be a recurring pattern with the tobacco witnesses or witnesses that have been invited here by tobacco people.

There has been a recurrent statement made by my colleagues in the back that these witnesses are independent, and I think it's pertinent for the record and for the public in general and for the posterity of this record, after these proceedings, that it be established whether or not these witnesses have any links that go beyond and have a history or pattern or recurring pattern of involvement with the tobacco industry and their attorneys.

DR. NEWELL: Your Honor, I'd like to make a comment, if I may, please.

JUDGE VITTONE: All right. Go ahead.

DR. NEWELL: I came here, basically at the request of OSHA, to provide information, and I did it willingly and actually I wanted to be a part of this even before anybody at Philip Morris asked me to participate, because I've been concerned, as I told you, Ms. Sherman, about the quality of government research, in some cases, and in the way procedures and practices that the regulatory agencies require of others, they don't follow themselves. And that's in the literature. It's well known.

And, sir, I resent thoroughly your intimidation that I can be bought. It is not so. You may think that's not so.

I am not here, sir, to take this kind of -- don't let me start to swear -- but I don't think this is proper. This is not a court of law, and I don't want to be sitting up here trying to defend myself against a technically assumed prosecuting attorney.

JUDGE VITTONE: Okay. Excuse me a second.

It seems to me he has identified himself as being here on behalf of Philip Morris. While some people

have -- we've gotten into this in detail in the past, I don't see that this is crucial, detailed inquiry.

If they want to provide that information, that's fine, but if he objects to it, I'm going to sustain his objection. He has identified himself as a witness for Philip Morris on behalf of them and, for the purposes of the record for the Occupational Safety & Health Administration, I think we have adequate information in that area.

MR. KLOK: Thank you, Your Honor.

JUDGE VITTONE: Okay.

MR. KLOK: Mr. Newell, you were retained, as you stated, by Philip Morris, and I'm just curious whether or not you asked them about any of this CTR Special Project funding or whether you were involved in any of their CTR Special Project funding in your work with them?

DR. NEWELL: I think, Your Honor, I've already answered that question, and the answer is no to your question.

MR. KLOK: Your Honor, I'm only trying to establish whether or not --

DR. NEWELL: You're impinging my credibility, sir, and that's what I resent.

MR. KLOK: I don't think I'm doing that, Your Honor.

JUDGE VITTONE: We have an answer. He said no.

MR. KLOK: Thank you, Your Honor.

JUDGE VITTONE: Okay.

MR. KLOK: I think what I'm trying to establish, if I may just say this, is if he has access to other information that may be helpful for OSHA in determining its regulations, through special projects that Philip Morris has conducted, I just want to know whether or not he could help OSHA in acquiring that information. I don't think my request is unreasonable.

JUDGE VITTONE: You could ask him if he has access to that information.

MR. KLOK: That's all I was asking, Your Honor.

DR. NEWELL: I'm very happy to answer your question to the best of my ability.

The only information I have is what is in the published literature, and what you're talking about, assumed other studies, I know nothing about.

MR. KLOK: Okay. That's all I was asking. Thank you, Mr. Newell.

If I may ask, again, for something further here.

If you knew that your employer did have these studies and would have helped you in providing information for this statement, is that something that you think would be important for you in helping you determine whether or not there is sufficient animal studies evidence?

DR. NEWELL: That's a hypothetical question, sir, and I just don't get into those kind of situations.

MR. KLOK: But you would be interested if that information existed?

DR. NEWELL: I don't know what kind of information you're talking about.

JUDGE VITTONE: Dr. Newell, I think you're turning away from the microphone.

DR. NEWELL: I'm sorry. I don't know the kind of information you're asking for.

MR. KLOK: Well, let me retrack maybe here.

You did state earlier that your reason for being here was that it was important for scientific research, and you were concerned about whether or not there was sufficient scientific grounds for passing the regulation, whether the animal studies themselves, in particular the ones you addressed in your statement, were conducted appropriately.

My question really is, if there was additional information that would help you come to that conclusion or give any guidance to OSHA, do you think that's information that you would have liked to have had access to?

DR. NEWELL: I don't know that there is any further information conducted; what I think is a rather extensive survey of the literature and went through MedLine and all the rest, and this included international publications as well as domestic, and that's the extent of the information I have and which I worked from. It's in the published literature, and nothing else.

MR. KLOK: All right. Were you aware that there's over 1000 CTR Special Project documents that are under confidentiality order?

MR. ANDRADE: Your Honor.

JUDGE VITTONE: Mr. Andrade.

MR. ANDRADE: D. Newell -- and it is Dr. Newell -- has testified that he is not aware of CTR Special Projects and that he has not been the recipient of a CTR Special Project.

Now, once again, we are here discussing an issue that is relevant to the litigation that these gentlemen are involved in that has no place in this OSHA proceeding. This is an attempt to try to gain whatever information they can, that might further their interest in private litigation.

Now, Dr. Newell made it perfectly clear from the outset that he was here at the request of Philip Morris. I submit that the only recurrent theme that we're seeing in these proceedings is an attack on the integrity of distinguished scientists who come here with well thought out scientific opinions to assist OSHA in evaluating the scientific evidence on environmental tobacco smoke, and we have questions that are only designed to attack the individual and to obtain information that can be useful in some way, shape, or form in private litigation.

I think Dr. Newell is ready to answer any questions on the subject of environmental tobacco smoke and lung cancer in animal experiments. That's what he's here to do today, and I submit this is just very inappropriate.

MR. KLOK: Your Honor, if I may. No disrespect to Dr. Newell, it was the tobacco attorneys, and specifically Mr. Rupp, stated that these scientists were here as independent scientists. All we're trying to establish is whether or not there are any grounds for bias. I think it's important for the record to establish that.

JUDGE VITTONE: Okay. Well, he says he hasn't seen any of these; he doesn't know and hasn't seen any information from CTR.

MR. KLOK: I'll move on.

JUDGE VITTONE: Okay. So you'll move on.

MR. KLOK: Thank you, Dr. Newell. I do not mean to be in any sense derogatory to you or your work.

DR. NEWELL: Thank you.

MR. KLOK: One minute, please.

(Pause)

MR. KLOK: I have nothing further, Your Honor.

Thank you, Dr. Newell.

DR. NEWELL: You're welcome.

JUDGE VITTONE: Mr. McNeely.

MR. McNEELY: Good morning, Dr. Newell. My name is Hugh McNeely, and I'm also an attorney involved in the Costano litigation in New Orleans, but here for the purposes of these hearings, on behalf of the AMA, ETS victims, witnesses 156, 1411, and some trade unions, witnesses 171 and 172.

In listening to your initial introductory remarks, I noted that you belong to a number of societies and associations, and I may have just missed it, but you also belong to an organization or Council called the American Council on Science and Health?

DR. NEWELL: No, I do not -- yes, I do. Yes, yes.

MR. McNEELY: Okay. That was omitted from your statement earlier?

DR. NEWELL: Well, I act only as 1 of some 200 people that are called scientific advisors. I wouldn't say I'm a member of it, no.

MR. McNEELY: Okay. Are you on the Board of Scientific and Policy Advisors?

DR. NEWELL: Correct.

MR. McNEELY: And you were so a policy advisor on that Board in June of 1962?

DR. NEWELL: No.

MR. McNEELY: You may want to get in touch with them because they certainly have you listed.

DR. NEWELL: You said '62.

MR. McNEELY: Yes, really, I did. I apologize. It's 1992.

DR. NEWELL: I believe so, yes.

MR. McNEELY: Okay. I was just interested. Could you tell me what is the American Council on Science and Health?

DR. NEWELL: Well, as you well know, have a list of the members, it's an organization that attempts to be objective in its evaluation of various issues, and I think you are probably also aware that it was resoundingly attacked by consumer's union unfairly and inappropriately, and I see the low means that they used to attack the group that has people everywhere from presidents of universities to professors, then a few people like myself, that are asked to provide opinions on mostly on manuscripts. Never been asked to take a position in a political matter, and I fully know what you're leading up to, but --

MR. McNEELY: Okay. Well --

JUDGE VITTONE: Doctor, Doctor, may I suggest that you don't anticipate the question.

DR. NEWELL: Okay.

JUDGE VITTONE: Okay? I think we might move a little faster.

MR. McNEELY: If I understand what you've described, it's a group of what you would consider prestigious scientists who are also concerned with quality research and sound science?

DR. NEWELL: Yes, in terms of interpretation of it, yes.

MR. McNEELY: Then I guess what you were anticipating was my questions concerning the American Council on Science and Health, publication in June of 1992, wherein it -- and I would like to know your participation in this and whether you agree -- where the American Council on Science and Health joins with the U.S. Public Health Service, World Health Organization, the American Cancer Society, the American Lung Association, the American Heart Association and countless other organizations, concerned with public health and condemning cigarette smoking as the major health hazard facing economically developed countries and a growing problem in the developing world.

Do you recall that being the pamphlet that is copyrighted by the American Council on Science and Health?

DR. NEWELL: I know the pamphlet exists. I have not seen it or read it.

MR. McNEELY: Okay.

DR. NEWELL: Most of them come out, but I know Elizabeth Whalen's position on this issue.

MR. McNEELY: Okay. But would you agree with that as far as a statement on policy by respected and distinguished scientist interested in quality research and sound science that that is a statement of policy that you can agree with and enjoin?

DR. NEWELL: Not necessarily. Sir, I'm here to discuss and talk about environmental tobacco smoke and not on direct smoking, and that gets into an entirely different issue.

MR. McNEELY: But there's another within the Executive Summary, which is also in the publication of June 1992, relative to the issues that we're here for today, there is a statement, quote:

"Non-smokers exposed to environmental tobacco smoke are also at greater risk for certain diseases." And the preface to that is, of course, discussing the exposure particularly of pregnant women and children as their health being jeopardized by exposure to ETS.

Is that something you can agree with?

DR. NEWELL: Not on the basis of what I know about ETS. I would say there's no scientific foundation for it.

MR. McNEELY: So you would put yourself outside in disagreement to the policy announcement of what you have described as an organization of distinguished scientists and people who are likewise interested in quality research and sound science? You put yourself outside of that?

DR. NEWELL: No, I don't necessarily put myself outside it. There's a group, as I told you, of some 200 people, and I'm sure there are others that are on that list that would agree with my position.

There's no reason that you have to be bound and sealed and be a member of the Ku Klux Klan in order to agree with Elizabeth Whalen's position on that.

MR. McNEELY: Do you equate Elizabeth Whalen in that organization with the Ku Klux Klan?

DR. NEWELL: No, I don't.

MR. McNEELY: Okay. I would like to get back to your comments. This is the comments, and I guess it's

3-18-92; your comments that you submitted.

DR. NEWELL: Yes.

MR. McNEELY: That was in response to the request for information on indoor air quality issues.

DR. NEWELL: Right. Right, right.

MR. McNEELY: I believe you were discussing the study by Nancy Jean Haley, et. al., 1987, Sidestream Smoke Uptake, by sealing golden hamsters in an inhalation bioassay.

DR. NEWELL: Yes. That's the one from the American Health Foundation, right?

MR. McNEELY: Yes, sir.

DR. NEWELL: In your brief critique of that particular study, I noted that you made the comment that there were no lung tumors reported, and I think you also commented on the fact that they did apply -- there was a grant renewal application; you also commented on that as well.

But my appreciation of the grant renewal application, in that application, they did state that at least one of the animals exposed to mainstream had an adenoma of the lung and that two of the sidestream exposed animals had this same lung tumor. Of course, none of the controlled or sham-treated animals presented lung tumors.

I did not see that in your critique, and I think, if I was to just read your description, at least I would understand that there were no tumors reported.

Was that an error of omission or was there some reason that you left that out?

DR. NEWELL: No, I didn't recall that particular issue. But I think, sir, you should realize this is a study with mainstream and sidestream, and it's cited here in this document because that's one of the few studies that are available.

I think you should also be good enough to also note that this experiment was discontinued 18 months because there's been so many deaths of the animals, which is a reflection on the quality of the way that work was done, which really completely vitiates the reliability of any of the data they have.

MR. McNEELY: Again, I don't have the advantage of your experience and education, so a lot of my questions, I hope that they make some sense to you in trying to understand some of your critiques.

Again, I'm referring to your comments of

7-15-94.

DR. NEWELL: Okay, yes.

MR. McNEELY: This is in reference to the Otto & Elmhurst.

DR. NEWELL: What page was that on? I guess they're not numbered. Yes, they are. What is the exhibit number?

MR. McNEELY: The exhibit number is 4-247.

DR. NEWELL: Okay.

MR. McNEELY: I'm sorry. I tried to mark your page and paragraph but I didn't do that on this one.

DR. NEWELL: Yes, okay. I'm with you.

MR. McNEELY: Also, I'm going to refer to the Lutenberger.

DR. NEWELL: Yes.

MR. McNEELY: Okay. The Otto & Elmhurst studies, I appreciate, have shown higher percentages of lung adenomas in smoke exposed mice as compared to the respective controls.

Additionally, in the Lutenberger study, results showing that the rate of tumors among mice exposed to the gas phase were greater than animals exposed to the whole smoke.

Yet, in your comments you state that the long-term exposure of mice to gas phase cigarette smoke had no effect on the spontaneous tumor rate while cigarette smoke caused an increase in spontaneous tumor rates.

The question is -- and I believe you stated that the authors noted that there was no significant difference in the spontaneous tumor rates between the smoke of exposed mice and the unexposed controls.

I'm just wondering, is there a contradiction there or can you explain?

DR. NEWELL: Well, first of all, the incidence was very low.

Secondly, the authors stated you did have the same kind of tumors occurring in the unexposed mice as you did in the exposed, but only the higher rate. I believe it's a difference between 2 and 4 percent, a very low level.

The point is, the same kind of tumors occurring in the unexposed as the exposed, and what you're getting is perhaps an extenuation of the incidence of these. The point is, there's no causation that could be demonstrated that someone might try to draw from this. There's only an increase what was going to occur with that strain of animals.

MR. McNEELY: So you would disagree that the enhancement in the Lutenberger study, caused by the chronic inhalation of gas phase, cigarette, you would disagree that that establishes a causal association between the tobacco smoke and the lung cancer?

DR. NEWELL: Definitely. Yes.

MR. McNEELY: Now, I understand you have termed most of your testimony, or tried to term all of your testimony, in terms to your review of the animal studies with regard to lung cancer.

This question may have been asked. If it has, I apologize. But with regard to the carcinogens, you do agree that there are carcinogens both in the mainstream and sidestream smoke?

DR. NEWELL: Certain studied have been done on that, but I also bring to your attention the carcinogenicity, if you will, of any particular material is related to its dose.

MR. McNEELY: Okay.

DR. NEWELL: There's a practical threshold of almost anything that we are exposed to. Some theoretical people don't agree with that, and they say particularly the EPA uses the straight line extrapolation, which I think is insupportable scientifically, but it makes for good theory. MR. McNEELY: So that I can understand what you just said, you believe that as far as the carcinogenicity is dependent on dose and as far as any threshold levels, if I understand your previous testimony, you do not know what that threshold level is?

DR. NEWELL: Exactly.

MR. McNEELY: In preparation and consideration of the animal studies with lung cancer, I was just wondering, did you review the Fontham, et. al., study on lung cancer and non-smoking women?

DR. NEWELL: No. My concentration has been entirely on animal studies.

MR. McNEELY: Are you familiar with the Fontham studies?

DR. NEWELL: No, I am not.

MR. McNEELY: These proceedings, as they relate to a rulemaking for the American worker, would you agree that if these proceedings and the evidence goes on the side of some of your colleagues in the American Council on Science and Health, that the weight of the evidence determines that non-smokers exposed to environmental tobacco smoke in the workplace are being exposed to significant risk for disease, you agree that it would be appropriate that this rulemaking go forward and be implemented?

DR. NEWELL: You just used the phrase that I do not support, and that is the general political position using the weight of evidence.

It is not a scientific term, actually. It's an attempt to try to bring often a lot of disparate data together and say that leads you in that direction; I'm sorry, I can't agree with you.

MR. McNEELY: But you will admit the possibility that you may be totally wrong in your opinion and that these scientists who have found a link, or at least a significant link, to ETS and disease through workers exposed in the workplace, you would admit the possibility that you're totally wrong and that the regulation should go forward?

DR. NEWELL: No, I wouldn't admit that I'm totally wrong, and I don't see that there's data in the literature to support it.

MR. McNEELY: My question: You would admit the possibility that you were --

DR. NEWELL: Sure --

MR. McNEELY: -- absolutely wrong?

DR. NEWELL: -- there's always a possibility. No. There's a possibility that something might happen would be different, but I wouldn't say I'm absolutely wrong until you can show me the data as such, and I'm waiting to see that.

MR. McNEELY: Thank you.

JUDGE VITTONE: Thank you, Mr. McNeely.

We're going to take a short recess.

JUDGE VITTONE: We're back on the record, please.

Mr. Andrade, as I understand it, Mr. Weinberg is not going to be asking any questions, so you can come on up. Let me ask you one question while he's on his way up, Doctor.

Talking about these dog experiments, and I noted that you said that in the experiments using rats and mice that you could have 50 to 70 in each group. How many dogs do you need, could you use?

DR. NEWELL: The number of dogs that have been used in any of these --

JUDGE VITTONE: I'm not a dog lover, by the way.

DR. NEWELL: I understand, but I'm not trying to be evasive. Basically, the size of your experimental group tends to be constrained by costs and the expense.

JUDGE VITTONE: Yes.

DR. NEWELL: I can recall there's some major studies that were funded by FDA on the essential carcinogenicity of certain dyes, and this goes back 10 or 20 years go. It went on for a long time.

No one outside the government could afford the extensiveness, the size of the studies that were done, and that also includes a lot of the radiation type studies that have been done with dogs at various universities.

I remember, particularly Utah and UC Davis both had 50 to 100 dogs in each particular treatment group, but for the most part you'll find 4 to 6 dogs per treatment group, and it's been generally accepted on the basis. Sure, you'd like to have more.

Ms. Sherman was asking, you're always looking to the potential of not getting an outlier that would otherwise show up if you had more animals.

JUDGE VITTONE: I know that -- I've been informed, anyway -- with respect to the mice you have to be careful about where they come from and their breeding and that kind of thing.

DR. NEWELL: Yes. Some of them carry inherently certain viruses, if they aren't careful, they die off before you get the study underway. The housing has to be right. That's one reason why you look carefully to maintain the humidity. You can get certain kinds of tail rot that some strains of mice are affected and just kills off the total experiment.

JUDGE VITTONE: Do you have to be that careful also with respect to an animal, like a dog?

DR. NEWELL: Not quite as much. Actually, I've run studies with dogs and outside runs at times, so you don't really need the temperature control that you get with the mouse or a rat. The environmental conditions under careful rates.

JUDGE VITTONE: But you can't go down to the pound and pick up a half dozen dogs?

DR. NEWELL: Not really. The use of pound-type dogs has dropped off considerably because of concerns by various animal activists, that you're taking someone's pet and using them for research and so forth.

In times past, the pound dogs were used particularly by pharmacologists for what we call acute studies, where they'd give them a particular drug and then maybe what affect it might have on the heart or respiratory system or something like that. Then the dog is sacrificed, and that's gone. So you don't have the concern about the quality of the dog.

Breeding dogs hopefully have had their conditions pretty well addressed, but as was pointed out this particular study that came out of Michigan, used dogs that not only did they have lung worms but I bought some from there one time, and they were just hyper-excitable and very hard to handle in a laboratory environment.

JUDGE VITTONE: Okay. Thank you.

Mr. Andrade.

MR. ANDRADE: Dr. Newell, I'm Tony Andrade representing Philip Morris. Let me start by asking you a couple of questions that relate to Mr. McNeely's examination.

Mr. McNeely was talking about adenomas when he asked you a series of questions on a number of animal experiments that are mentioned in your materials.

Now, as I understand it, these experiments were designed to answer the question: Does exposure to tobacco smoke, be it mainstream smoke or sidestream smoke or environmental tobacco smoke, cause lung cancers.

Was that the design of the experiment?

DR. NEWELL: That's my understanding, yes.

MR. ANDRADE: Now, Mr. McNeely asked you questions about adenomas occurring in those experimental animals. Are adenomas cancers?

DR. NEWELL: No. Adenomas are classified as a benign tumor.

MR. ANDRADE: They're non-invasive, benign growths?

DR. NEWELL: Exactly. Right.

MR. ANDRADE: They are not the disease endpoint that those experiments were designed to evaluate?

DR. NEWELL: That's correct. Certainly were not malignant type of tumors.

MR. ANDRADE: And adenomas are not relevant, biologically, to the question of whether or not environmental tobacco smoke exposure was as lung cancers in humans; is that correct?

DR. NEWELL: That's right.

MR. ANDRADE: There was also a discussion concerning the number of adenomas that were observed in various experimental groups. If you have 100 mice, say, that are exposed to tobacco smoke in some form, and you see two adenomas, but in the control group it is not exposed to tobacco smoke, you see one adenoma, is that difference enough for a toxicologist to come to the conclusion that exposure to tobacco smoke caused the adenomas?

DR. NEWELL: No. Certainly, when you get large experimental groups, such as you're mentioning here, you get 1 or 2, that is not statistically significant and necessarily be related at all to causation.

Of course, as we saw, they cited in the paper the kinds of tumors that were formed, pathological histology were the same, and it was only a matter of a slight increase, but the numbers are so small it's insignificant.

MR. ANDRADE: Those small numbers would most likely be attributable to the normal background rate of disease in those experimental animals?

DR. NEWELL: That would be my judgment, yes.

MR. ANDRADE: If you simply took the control animals and let them live out their lives happily on the shelf, you would still get a certain number of adenomas in those animals, wouldn't you?

DR. NEWELL: Apparently so. Various strains of animals, unfortunately, do carry the likelihood of developing certain kinds of tumors. That's well established in the literature. Not only in mice but in rats.

MR. ANDRADE: And it's also established for the various species of animals that you discussed in terms of the tobacco smoke, inhalation experiments; it's also true, isn't it, that those same animals will spontaneously develop certain background rates of lung cancers as well?

DR. NEWELL: Could be. Could be. I'd have to go back and look at the literature on that particular strain to be able to make a definitive statement.

MR. ANDRADE: Let me ask a general question about the value of toxicology to the OSHA panel.

We've had considerable testimony on the epidemiology with respect to environmental tobacco smoke and lung cancer. That epidemiology has been criticized for failing to control for a number of confounding factors.

I'd like to ask you a series of questions to delve, whether or not toxicology can perhaps be of more value to the OSHA panel with respect to evaluating the impact of confounding factors on the epidemiological studies.

In an animal inhalation experiment, using some form of tobacco smoke, do we know the genetic makeup of the animals that are being tested?

DR. NEWELL: Usually. Not always, but usually so. MR. ANDRADE: Generally, you can select an in-bred strain where the genetics are virtually identical?

DR. NEWELL: Right.

MR. ANDRADE: So any lung cancers that could be attributed to genetics, should be controlled for since all the animals have the same genetic make-up, correct?

DR. NEWELL: And if you have enough history on this, you could have some information about the potential, quote, "spontaneous", end quote, incidence of tumors.

MR. ANDRADE: So in that sense, the toxicological experiment, animal experiment involving tobacco smoke might be superior to an epidemiological experiment where every human in that experiment has a different genetic make-up and therefore different chance of developing lung cancer from genetic causes. Correct?

DR. NEWELL: Very much so. Certainly, it's been cited by various key people, particularly at the NIH, that there is no one human. We are a whole series of different individuals because of the variability and genetic make-up and background, and so on, and some people are much more susceptible, others are more resistent to a stress situation.

MR. ANDRADE: We've had a lot of testimony in the ETS and lung cancer epidemiology area that it's very difficult to assess a dose; that is, how much of environmental tobacco smoke non-smokers may have been exposed to. That is a problem with those studies.

But in an animal inhalation study, you can carefully measure dose of cigarette smoke that the animals are being exposed to. Isn't that correct?

DR. NEWELL: Yes, certainly.

MR. ANDRADE: That's measurable, it's controlled for, and it's quantitated to a very high degree?

DR. NEWELL: That's correct.

MR. ANDRADE: So, again, that would be a strength that the animal studies would have, that the epidemiology in this area does not have?

DR. NEWELL: That's correct.

MR. ANDRADE: With respect to other confounding factors that are thought to cause lung cancer in humans, such as diet, things such as environmental exposures, where you live; workplace exposures, for instance, each of us, we were in ETS and lung cancer epidemiology study would have different diets, would have different occupational exposures based on where we lived our lives. We would have different occupational exposures, and that might account for lung cancers.

In an animal experiment, we control the environment, don't we?

DR. NEWELL: We control the environment. And, also, Mr. Andrade, an important other factor is that with the animal experiments you know how much these animals receive in terms of dose for how long a period of time.

When you get into epidemiology studies, and particularly retrospective ones, confounders can be very extensive and weakens the results that people try to draw from those kind of studies.

MR. ANDRADE: And the diet is controlled? All of the animals receive the same diet?

DR. NEWELL: Sure.

MR. ANDRADE: Unlike the human epidemiology. All of the animals live their lives in the same laboratory so they're not subject to environmental occupational exposures that humans are, obviously?

DR. NEWELL: Certainly.

MR. ANDRADE: Would you agree, again, that those are strengths that we have in an animal inhalation study that are lacking in a human epidemiology study?

DR. NEWELL: Certainly. They minimize the number of confounders, if you will, or the questions of other aspects of stresses that might affect the outcome or attempt to interpret the outcome.

MR. ANDRADE: Would it be fair to say that, in essence, an animal inhalation study involving environmental tobacco smoke or mainstream smoke, where all of these variables are controlled for and the only question left is one group receives the agent tobacco smoke, the other group is not exposed, in essence, is a pure inquiry into the question of whether or not tobacco smoke causes lung cancer, we would have in an epidemiological study that has all of these factors uncontrolled?

DR. NEWELL: Certainly. The more that you can control the environment and all of the other factors you just listed, the lesser the probability it questions the reliability of the information.

MR. ANDRADE: Dr. Newell, you mentioned in your testimony this morning I think at least two government-funded or government-conducted animal inhalation studies involving tobacco smoke that failed to show a relationship between exposure to tobacco smoke and the development of lung cancer, and in one case the exposure of the animals to environmental tobacco smoke -- tobacco smoke, excuse -- in the development of heart disease.

These you would characterize as negative studies?

DR. NEWELL: Very definitely.

MR. ANDRADE: I think that you testified these studies were not published in the peer review literature?

DR. NEWELL: They haven't been, that I have been able to find out. In fact, as I mentioned in my testimony, it was necessary to go through the various processes of trying to get information from the government records, which they didn't readily give up until we used the Freedom of Information Act process.

MR. ANDRADE: Would you consider this to be some evidence of publication bias?

DR. NEWELL: You said it, I didn't. Certainly, it raises a question about why there are a number of studies that have been undertaken that have not appeared in the scientific literature. Certainly, even the Hoffman study with the hamsters was not readily published in the open literature.

I believe, though, there's information we got on that, came out of a meeting that was held in Paris, and Dr. Haley presented some information, but it was not a full-blown type of a report as you would expect from a long-term type of study.

MR. ANDRADE: But having access to the complete data from these animal inhalation experiments, which were negative, would be helpful to you as a toxicologist in reading the question as to whether or not ETS has health effects in humans?

DR. NEWELL: Certainly. I think it's appropriate to have a broad balance in the literature, for both positive and negative information. Then you can better make a realistic judgment.

MR. ANDRADE: I wanted to ask you a few questions about, quote, "carcinogens in cigarette smoke," because I think there's some confusion in the record. Many times questions are asked that just refer generally to carcinogens in cigarette smoke.

As a toxicologist, when someone asks you if there are carcinogens in cigarette smoke, do you interpret that to mean that there's evidence that the compound is carcinogenic under the specific circumstances of a particular experiment or set of experiments?

DR. NEWELL: Yes. You've got a material that's been designated as a carcinogen, it's usually as a result of the particular study, and for the most part the chemical as such has been studied in its pure state, if you will; been added to a diet or inhalation, injection, or whatever. So that may have a response under those particular conditions, which are specific to the test for which you've obtained the data.

MR. ANDRADE: So if we take a compound -- we don't have to focus on a particular compound, but just one compound from tobacco smoke, mainstream smoke, as reported to be a carcinogen, means that in some experiment that compound was observed to be a carcinogen at some dose level. Correct?

DR. NEWELL: Yes. Certainly, the response that you're going to find is going to be based on dose, and the dose determines the dose, quote/end quote. It's getting to be a cliche.

And so that many people are exposed to chemicals wherein there is no response of the carcinogenic effect, and that goes on through many materials, and not necessarily in environmental tobacco smoke. Because if, indeed, everything is listed as a carcinogen and we accepted that as a real hazard, there wouldn't be anybody sitting in this room today because we've all been exposed to those by definition, on those specific studies.

So, indeed, you have to note what kind of concentrations people are exposed to particular material, to really define it. Is it a carcinogen under those circumstances.

MR. ANDRADE: The dose of that compound, in this particular experiment that we're discussing, could be tens of thousands, indeed, hundreds of thousands of times higher, and the concentration of that compound in mainstream smoke or environmental tobacco smoke.

DR. NEWELL: Could be.

MR. ANDRADE: And the route by which that animal receives that compound, it could be added in their food, it could be given to them in their drinking water, it could be injected directly into one of their systems, but isn't necessarily --

DR. NEWELL: Or inhalation, or whatever.

MR. ANDRADE: Or inhalation. But the experiment could have come to the conclusion that the compound is a carcinogen, not via the inhalation group; isn't that right?

DR. NEWELL: Oh, definitely. Certainly.

In fact, it's important to define the manner in which the material produces an effect.

MR. ANDRADE: And if a compound that's found in cigarette smoke were deemed to be a carcinogen, based on an experiment where it was fed to the animal or injected into the animal, that wouldn't necessarily have any relevance to that compound as found in environmental tobacco smoke as inhaled potentially by humans.

DR. NEWELL: It's possible. Certainly, it's possible.

MR. ANDRADE: And when someone says that a compound in cigarette smoke has been demonstrated to be a carcinogen in an animal test system, it doesn't necessarily mean that it's been demonstrated to be a lung carcinogen, does it?

DR. NEWELL: That's right.

MR. ANDRADE: That compound can be taken in a dose that's not representative of how it's found in environmental tobacco smoke, given to the animal through a route of administration that's not inhalation, and it could cause cancer in an organ other than the lung; correct?

DR. NEWELL: Well, yes, and that relates back to my earlier comments of this morning; and that is that chemicals, particularly using the NTP design, are the highest level that's used, often as bad as what we call the maximum tolerated dose.

And that could be many, many fold above the concentration that you'd find that material be it in food or water or tobacco smoke or environmental tobacco smoke.

The objective, of course, as I've said, and the people in the field well know, the defense of it is that you want to make sure you don't miss anything; let's shove it to the animals and see whether or not you can produce any adverse effects.

Of course, that's part of the way the drug studies are done, also, looking at -- devising side effects. But that doesn't necessarily relate to what we're going to have to be confronting when you get into materials that you have on a day-to-day basis.

MR. ANDRADE: Just because a compound that may have been identified environmental tobacco smoke, at some dose, through some administration, causes some cancer in some organ or some species, doesn't necessarily mean that that compound is carcinogenic to humans as it's found in environmental tobacco smoke?

DR. NEWELL: Very definitely so.

MR. ANDRADE: You were also asked a couple of questions by Ms. Sherman regarding hyperplasia.

A hyperplastic response, or hyperplasia, as seen in an animal experiment, that is not a response as specific to exposure to tobacco smoke, is it?

DR. NEWELL: Not at all, no. For the most part, it's usually considered a result of an irritation process.

MR. ANDRADE: As a general response to any inhaled irritant?

DR. NEWELL: That's right.

MR. ANDRADE: You could see hyperplasia just by breathing in perhaps polluted urban air?

DR. NEWELL: Very much so. Hot air, for instance, certainly would be an irritant that would cause those kind of changes.

MR. ANDRADE: If laboratory animals are just exposed to hot air, you would see hyperplastic changes?

DR. NEWELL: Depending on what temperature and how long and so forth, sure.

MR. ANDRADE: And on the dose and the duration.

And these types of changes are not thought to be distinct steps and inevitable progression towards the development of cancer, are they?

DR. NEWELL: No. Certainty not distinct steps. You allow that process to continue on over a long period of time, you see a non-genotoxic materials that, indeed, tumors do develop, but they're not DNA related where you get a change in the DNA structure.

For the most part, these are all reversible. You take the stress away, even where some of the tumors have occurred, you let them go on a long enough period of time and they regress.

MR. ANDRADE: So it's fair to say that hyperplasia is a normal response to an irritant that's reversible that has no clinical significance?

DR. NEWELL: It's an attempt at an adaptive process by the organism.

MR. ANDRADE: But you would agree that it has no clinical significance?

DR. NEWELL: No, I don't believe so.

MR. ANDRADE: Also, Ms. Sherman asked you a couple of questions concerning the appropriate size of animal groups and animal inhalation experiments.

Are you generally satisfied if the size of the various experimental groups meets the criteria that you showed us this morning for the national toxicological program protocol?

DR. NEWELL: That design is pretty well accepted by the scientific field that has to do those kind of studies, yes.

MR. ANDRADE: I believe the number --

DR. NEWELL: It always could be better.

MR. ANDRADE: I believe the number was approximately 40 to 50 animals per group.

DR. NEWELL: Per sex.

MR. ANDRADE: Per sex per group.

But there have been animal inhalation experiments using cigarette smoke that have used much, much larger groups; indeed, some that have used groups on the order of hundreds, or perhaps even thousands; isn't that correct? And I'm specifically referring to the Microbiological Associates' experiment.

DR. NEWELL: Yes, that was a large one, but that's unusual to have a study that size.

MR. ANDRADE: But the evidence you relied on today was not limited to animal experiments that had groups only on the order of 40 to 50 animals per sex per group?

DR. NEWELL: No. There's one study that I think I cited, whether or not I mentioned it, that had only five rats in the total experiment, and it went on for over a year.

MR. ANDRADE: Would you please take out your

July 15th, 1994 filing to OSHA, Doctor?

DR. NEWELL: Yes.

MR. ANDRADE: If you could turn to the second page. I think it's DX4-226, Moore & Resnick.

DR. NEWELL: Yes.

MR. ANDRADE: Ms. Sherman asked you a series of questions about this particular experiment, and I think there may be some confusion in the record.

This experiment involved mice that were exposed 300 times, or 15 minutes each time, to cigarette smoke? Is that right?

DR. NEWELL: That's what the literature said, yes.

MR. ANDRADE: This does not necessarily mean it was a total of 300 cigarettes, does it?

DR. NEWELL: No, no.

MR. ANDRADE: In fact, in most of these experiments, many cigarettes are smoked by machine, and the smoke is pulled, if you will, for each exposure, so that each exposure is the equivalent of receiving the smoke from numerous cigarettes. Isn't that right?

DR. NEWELL: That's correct. Again, the process and the method of exposure varies. Certainly if you get a large number of animals, there will be a number of cigarettes that are smoked all at the same time.

MR. ANDRADE: Okay. Now laboratory mice that are involved in these inhalation experiments only live 18 months to 2 years? Is that approximately correct?

DR. NEWELL: Two to 2-1/2, yes.

MR. ANDRADE: So if they received an exposure 300 times every other day, that would come pretty close to a lifetime exposure, wouldn't it?

DR. NEWELL: Yes, yes.

MR. ANDRADE: So in that sense, one cannot draw a comparison between these experimental conditions and the example Ms. Sherman gave you of a 1-pack per day smoker, smoking 300 cigarettes, 20 per day, for 15 days? That wouldn't be an appropriate comparison, would it?

DR. NEWELL: Not really. Again, the details,

Mr. Andrade, of the study itself are not there in order to really make a definitive statement for what Ms. Sherman was attempting to design, or your comment. I would have to go back and look at the literature and see what it is.

MR. ANDRADE: But even without having the study in front of us, you would agree, would you not, that being exposed 300 times for 15 minutes for a mouse at a certain body weight and a certain lung surface area is much different than the human smoking 20 cigarettes a day for 15 days?

DR. NEWELL: Sure. Sure.

MR. ANDRADE: Because the key concept is, is it not, concentration?

DR. NEWELL: Concentration and time.

MR. ANDRADE: We'd have to look back at the 300 exposures, we know for 15 minutes each, and see what the actual concentration was?

DR. NEWELL: Exactly.

MR. ANDRADE: In many of these experiments --

DR. NEWELL: They never measured them.

MR. ANDRADE: -- in many of these experiments, the concentration of the actual dose of tobacco smoke that the animals are exposed to, greatly exceeds what humans are routinely exposed to. Active smoking or, certainly, so-called passive smoking? Isn't that right?

DR. NEWELL: Could be. Yes.

JUDGE VITTONE: How much longer, Mr. Andrade?

MR. ANDRADE: Three more minutes.

If you could also turn in that same document to your note on the Dalby experiment, please. It's page three, the EX-4-77.

DR. NEWELL: Yes.

MR. ANDRADE: I think there may be some confusion in the record here as well. I think Ms. Sherman may have asked you whether the authors found that pre-neoplastic changes may represent carcinoma. But if you'll look at the last sentence, the next to the last sentence, I think it reads, "The author's comment that squamous nodules were observed in nine percent of the smoke-exposed animals and may," the underlined emphasis is mine, "represent pre-neoplastic changes."

Isn't the point here that these may represent some of these non-specific pre-neoplastic changes, and not necessarily that these pre-neoplastic changes may represent carcinomas?

DR. NEWELL: That's true. The way the histologists, pathologists have used in grading these tissue changes and I think anyone that's been close to this field realizes that pathology is an art and not a science. It's very difficult to get half a dozen pathologists together to look at the same slide and get everyone to agree on it.

MR. ANDRADE: Was this experiment a life time study?

DR. NEWELL: I would say so on the basis that these were rats, and it was for two and a half years. That pretty well approximates a reasonable duration of life for rats.

MR. ANDRADE: So Ms. Sherman's question about whether or not so-called pre-neoplastic changes might progress to cancers, one would expect to have seen that progression when you have a life time study and the animals are exposed for their natural life time to tobacco smoke, is that right?

DR. NEWELL: Certainly. You can only go on so long. After awhile your animals are just dying off because of old age and you still may not see any difference in tissue changes.

MR. ANDRADE: You were asked some questions about the Auerbach and Hammond beagle study.

DR. NEWELL: Yes.

MR. ANDRADE: You testified this morning that there was a National Cancer Institute study, I think, conducted at Hazelton that also used beagle dogs that were exposed to tobacco smoke.

DR. NEWELL: Right.

MR. ANDRADE: Did the results of that study, no demonstration of the production of lung cancer in those dogs, confirm your interpretation of the earlier Auerbach work?

DR. NEWELL: Confirmed it on the basis that there were no lung tumors established. The experimental design was much different in the two of them, but the outcomes were the same in terms of no lung tumors.

MR. ANDRADE: One final question. Isn't there a possibility that you are absolutely correct in your view that the animal data do not support the theory that ETS causes lung cancer in humans?

DR. NEWELL: Would you repeat that? That I am absolutely... As a scientist you've always got to quality your position.

MR. ANDRADE: Let me rephrase it. Isn't there a possibility that your opinion, based on the animal evidence that ETS may not be a cause of lung cancer in humans is a correct opinion?

DR. NEWELL: That's the way I feel.

MR. ANDRADE: Thank you very much.

JUDGE VITTONE: I think he's already answered that.

Thank you very much, Mr. Andrade.

MS. SHERMAN: Your Honor, I have a couple more questions if I might.

JUDGE VITTONE: Okay.

MS. SHERMAN: Referring back for a moment, Dr. Newell, to the Moore and Reznick study.

DR. NEWELL: Where are you?

MS. SHERMAN: It's on page two of your comments.

DR. NEWELL: July 15th?

MS. SHERMAN: Yes.

(Pause)

MS. SHERMAN: Look in the middle of the page, Exhibit 4-226.

DR. NEWELL: Okay. The review that they did, yeah.

MS. SHERMAN: Did I understand you correctly, that you do not know how many cigarettes were smoked in the 15 minute period?

DR. NEWELL: No, I don't.

MS. SHERMAN: I believe that Mr. Andrade discussed some epidemiological studies with you. Have you reviewed the epidemiological studies on environmental tobacco smoke and lung cancer?

DR. NEWELL: No, I haven't.

MS. SHERMAN: So you don't really have a basis for having an opinion on these studies, do you?

DR. NEWELL: Not the specific studies. I do have a feeling about the usefulness of epidemiology studies and their limitations because of the many confounders that can occur -- not always, but can.

MS. SHERMAN: But your remarks were not generally addressed to the specific studies at hand.

DR. NEWELL: No, because as I say, I have not reviewed them.

MS. SHERMAN: Did you do a literature search for all the animal studies on ETS and lung cancer or heart disease?

DR. NEWELL: On cancer, not on heart disease.

MS. SHERMAN: But you did a literature search for all the animal studies on ETS...

DR. NEWELL: That were available between the period... I think I stated somewhere between '86 and '92. I believe that was in my earlier submission. It was an attempt to try to be as comprehensive as possible on what was in the literature at that time.

MS. SHERMAN: There's been some discussion here of publication bias. You're familiar with the concept, I assume.

DR. NEWELL: Yes.

MS. SHERMAN: Have you ever had a negative study which you've tried to publish and which has been rejected?

DR. NEWELL: No, I can't recall such, although there, as you may know, there is a journal called the Journal of Negative Results...

MS. SHERMAN: No, I didn't know that. I know that...

DR. NEWELL: Most of it is tied in with acute studies rather than any long term type of work.

MS. SHERMAN: Is this a well established journal, this Journal of Negative Results?

DR. NEWELL: It's had difficulty in being very effective because the author was not able to get too many manuscripts of people willing to submit. They are just sort of embarrassed about coming up with negative studies and the like. Dick Perrot is the editor of that journal.

MS. SHERMAN: Is it considered publication bias if the researcher chooses not to submit a negative study for publication? Or is it considered publication bias if a negative study is rejected?

DR. NEWELL: Because it's negative in terms of results?

MS. SHERMAN: Perhaps because it's negative.

DR. NEWELL: I would support the latter view.

MS. SHERMAN: Getting back for a moment to our discussion on hyperplasia and metaplasia, do we know when hyperplasia is transformed into metaplasia?

DR. NEWELL: I would not feel competent to be able to give you that kind of... That's really a pathologist area. The big thing is we do know that usually those kinds of conditions are reversible if you take the stress away. The tissue effect you've seen disappear is when you take the stress away.

MS. SHERMAN: Under continued stress, what would happen, if you don't take the stress away?

DR. NEWELL: You're asking for a hypothetical question and I don't think it's appropriate. You have to look at each particular material. Some materials will just cause that alone. Others you may have, as I've said before, if you've got a stress and it's a non-geno type of stress, often... There are numerous examples in the literature. In fact I was involved in long term studies myself where you get only effects at the highest level and there's no dose response. That's another important reason for trying to categorize and better understand the material that you're working with.

MS. SHERMAN: One last question. Is hyperplasia induced by chronic exposure always reversible?

DR. NEWELL: To the best of my knowledge, yes.

MS. SHERMAN: Thank you.

JUDGE VITTONE: Doctor, thank you for coming today.

The one slide that was used by Dr. Newell in his presentation will be identified as Exhibit No. 221.

(The document referred to was marked for identification as Exhibit No. 221, and was received in evidence.)

Thank you, doctor.

DR. NEWELL: Thank you, sir. I appreciate the opportunity.

JUDGE VITTONE: Tomorrow, we will resume at 9:30. Our witnesses are Henry Beale, is that Dr. Beale?

MS. SHERMAN: Dr. Beale.

JUDGE VITTONE: A panel from the American Federation of Government Employees; Mr. Joseph King; Mr. Tom Pharr; and I guess one walk-on, Robert Edgar.

Ms. Sherman, is Dr. Beale going to be the first witness?

MS. SHERMAN: I believe that's fine with me. I have not checked with Dr. Beale.

JUDGE VITTONE: He's planning to be here at 9:30 then?

MS. SHERMAN: I hope so.

JUDGE VITTONE: If there are any other changes I don't know about them, but that's what I have on my list.

MS. SHERMAN: Do you want to call the audience attention to this puzzling letter from the Vermont Business and Restaurant Association?

JUDGE VITTONE: Apparently they believe they are coming on January 23rd. We have them listed as coming on January 20th.

MS. SHERMAN: Let me just mention for the record that Susan Kaplan of my office spoke with them yesterday afternoon, and they agreed to come on January 20th. However, the letter that we have from them is dated, well it was faxed, and it was dated 11:09 a.m. yesterday.

JUDGE VITTONE: Yes.

MS. SHERMAN: So it is unclear when they really are coming.

JUDGE VITTONE: Let me ask you this.

I understand they have a very short presentation.

MS. SHERMAN: Who?

JUDGE VITTONE: The Vermont people. I was just wondering, do you have any questions for them?

MR. McNEELY: I have questions for them.

JUDGE VITTONE: Anybody else have questions for them?

MS. SHERMAN: I believe that there will be questions for these people, Your Honor.

JUDGE VITTONE: All right. That takes care of my hope that maybe we could tell them they didn't have to come from Vermont, they could stay skiing or whatever they're doing.

(Laughter)

JUDGE VITTONE: We've got to clarify when they're coming, though.

MS. SHERMAN: I'll try to resolve this issue, but we seem to have two conflicting ideas here.

JUDGE VITTONE: Because Monday the 23rd we've got Dr. Steven Bayard, Dr. Daniel Ford, and also ICF Kaiser, Dr. Stanley Greenfield. I assume that's going to be a very full day.

MS. SHERMAN: Yes, it will be.

JUDGE VITTONE: The 20th, we have this Association for Commercial Real Estate, AFL-CIO, United Steelworkers, Dr. Benda from the Chelsea Group, and AIHA.

MS. SHERMAN: American Industrial Hygiene Association.

JUDGE VITTONE: Okay. That's going to be a pretty full day too, even if the Vermont people do show.

MS. SHERMAN: Yes. I agree with you.

MR. RUPP: Your Honor?

JUDGE VITTONE: Yes, Mr. Rupp.

MR. RUPP: With apologies if I become an agent for prolonging these festivities, but particularly as the Monday, July 23rd is now starting to break out, I really...

MS. SHERMAN: July 23rd, Mr. Rupp?

MR. RUPP: January 23rd.

(Laughter)

JUDGE VITTONE: You really do want to extend these festivities!

MR. RUPP: Your Honor, January 23rd. I just don't think that day is going to end on the 23rd. That is, as with many of the very important substantive witnesses who have appeared at our request whose examination has taken most if not all of the day, and occasionally all of the day, which we do not regret, we welcome. The examination of Drs. Ford and Bayard who are OSHA witnesses, I think could quite easily each take the better part of a day.

Now it may be that the solution to that would simply be to ask either Mr. Bayard who is local and who often appears here for his own information; or Dr. Ford, and I'm not sure where Dr. Ford is from; to be at the ready so that they can appear on the next day. But I think it would be a disservice to the record if the parties to the proceeding were unable to ask the kind of questions that I think the record deserves to have asked of these two gentlemen.

MS. SHERMAN: I think we're going to have to do the best we can, Mr. Rupp. We can try to start the hearing earlier that day, but I believe that there are scheduling problems with Dr. Ford, and I believe that Mr. Bayard, he may be a doctor, I don't know, will be out of the city after that day.

MR. RUPP: If we could ask you to check on that specifically, but if we are going to be going on for at least a couple of week period after the 23rd, rather than be the hostage of happenstance here as this day has begun to fill, and not be able to have the kind of discussion that Mr. Martonik and others asked that we have here, I think we ought to reschedule these important people if that proves to be necessary, rather than compromise the record itself, which we have gone to great lengths to try to void in this proceeding. So if Dr. Bayard, who has come repeatedly to the hearings, and indeed has taken the chance to examine others, has a day trip on the 24th, we could visit his testimony on a later occasion.

All I'm saying is, I think the last option we should pursue or let ourselves get in the position of having to accept is one in which examination of Dr. Bayard or Dr. Ford is artificially limited, particularly when Dr. Bayard is local and can easily be here on most days.

JUDGE VITTONE: Will you explore that with him?

MS. SHERMAN: I will explore it. I don't know how we're going to come out.

JUDGE VITTONE: With respect to that day, ICF Kaiser is also listed as a potential witness. I know nothing about what they're going to testify to. Do you have questions for them?

MS. SHERMAN: Yes.

JUDGE VITTONE: Does anybody else know anything about ICF Kaiser at this point, that they may be asking questions?

MR. McNEELY: We don't really contemplate asking significant questions.

MR. RUPP: Your Honor, I have not looked at their testimony yet, so I assume that we will have questions, but I can't tell you how lengthy they will be.

JUDGE VITTONE: What are they testifying about?

MS. SHERMAN: I believe models. I think it's exposure models, Your Honor.

MR. RUPP: In the past, those examinations have tended to take several hours.

I'm really just urging that we not walk up to this day, put people at great inconvenience because they have prepared, people coming in from out of town who have expectations, and then we realize that we have a dilemma that we all should have been smart enough to see in advance and resolve for the convenience of everybody who's participating.

JUDGE VITTONE: Mr. Rupp, you've raised the issue. I think she's going to look into it. Thank you.

We might as well go over the rest of the schedule because the only remaining part of the schedule after tomorrow is next Tuesday, Wednesday, Thursday, we have the R.J. Reynolds Panel. Also on Thursday we have Professor Hedge returning for examination, and also a Gene Davidson?

MS. SHERMAN: I don't know anything about that.

JUDGE VITTONE: That's what I have listed here, a Gene Davidson.

MS. JANES: He's a citizen.

MS. SHERMAN: A walk-on?

MS. JANES: No.

JUDGE VITTONE: He's got a docket number.

MS. JANES: We had a valid notice he was going to appear. He was supposed to be here on Monday and he called said that he would have to appear later in the hearing.

JUDGE VITTONE: Do you know anything about him? what is he testifying to?

MS. JANES: I don't recall. I believe he's a citizen. I can get his notice.

JUDGE VITTONE: I can't remember Professor Hedge. What is he going to talk about? I remember the name and everything, but...

MS. SHERMAN: Exposure studies, Your Honor.

JUDGE VITTONE: Okay. So his examination could be substantial also.

MS. SHERMAN: Yes, but don't forget, that's going to be the third day of R.J. Reynolds.

JUDGE VITTONE: You expect everybody to peter out, huh?

MS. SHERMAN: Well, I don't know. Ms. Ward seems to think that we have allotted more than ample time for them.

JUDGE VITTONE: Friday is when we get into the AFL-CIO and the Steelworkers and that group. Okay.

We will resume tomorrow morning at 9:30 in this location.

Thank you.
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