Document GmVw3nVRYreg73bEgNqxnv9JN
ASBESTOS BIOEFFEGTS RESEARCH FOR INDUSTRY
Medical Series, Bulletin No. 11
4400 Fifth Avenue Pittsburgh. Pennsylvania
1966
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FOREWORD
During the past year, a number of industrial materials have come under attack in public news media as a result of heightened public interest in the environment. The potential of such materials to adversely affect the health of the general population through environmental contamination has been raised,
One such material is asbestos. There have been articles in the profes sional literature** ^ and in the lay press which present highly exaggerated views
of the nature and extent of the potential problem. Prompt criticism has followed pointing to erroneous interpretation of existing facts and publication of misinfor mation.
At the suggestion of several of its members. Industrial Hygiene Foundation held a meeting on July 19. 1966 to summarize what industry is doing to develop information to protect the health of its employees and the public from potential environmental hazard. Such information should be of considerable value to all those responsible for planning of environmental and occupational health research, whether in industry, universities or government.
it is appropriate that Industrial Hygiene Foundation, a nonprofit research association of industries for advancement of health conservation in matters related'to industry's operations, products and wastes, should assist in development of national environmental and occupational health research to help insure that industry's needs are provided for at all stages of program development.
-------------------------
1. Thomson, J.G. and Graves, W.M, "Asbestos as an Urban Air Contaminant. '*
Arch. Path. 81:458, May 1966.
%
2. Thomson, J.G. and Graves, W.M. "Asbestoais in Urban Populations."
JAMA 196:732-733, May 1966.
3. Anonymous. "Asbestos: Awaiting 'Trial*." Chem. Week, p. 32, Sept. 10, 1966.
4. Gross, P. Letter to Editor "Today's Pressing Question--How Safe is Urban
Air." Arch. Path. 2:195, Aug. 1966.
5. deTreville, R.T.P. Letter to Editor. Arch. Path, (to be published)
6. Gross, P. Letter to Editor. JAMA, (to be published)
7. Hackney, R. Letter to Editor. Chem. Week, p. 7, Oct. 8, 1966.
8. Brown, M. C. Letter to Editor. Ibid.
9. Editorial Note (following refs. 7 and 8). Ibid.
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1.
Subject; Summary of Needs and Plana for Asbestos Research
The purpose of this session of the Industrial Hygiene Foundation
Management Planning Meeting, held in. the Hunt Room of the Webster Hall
Hotel on July 19* was (l) to help develop a better concept of the asbestos
industry's environmental and occupational health research needs and what
ms being done to meet them and (2) to provide the U. S. Public Health Service
Surgeon General with a summary report and any recommendations which may
be developed from the meeting to aid in setting, clarifying, and reaching
sound and realistic health conservation goals in the national interest.
The meeting was sponsored by the Foundation's Policy and Plan
ning Committee,
Those attending the meeting were:
Name
Company
Bowman, H*M. Colwell, M.O. Cralley, L. J. Davison, E.K. deTreville, R..T.P. Edwards, F.H. Grant, L. B. Groaa, Paul Hatch, T.F. Hazard, W,G. Minard, David Schrenk, H.H. Smith, F.W. Smith, K.W. Smyth, H. F. Wright, G.W.
*.
Thiokol's Reaction Motors Division Aluminum Company of America U.S* Public Health Service Daviaon Sand in Gravel Company Managing Director of IHF Owena-Corning Fiberglaa Corporation Pittsburgh Plate Glass Company Director of IHF Research Laboratory University of Pittsburgh Owens-Illinois Glass Company University of Pittsburgh Secretary, IHF Board of Trustees Mine Safety Appliances Company Johns-Manville Corporation Mellon Institute
St. Luke's Hospital
t
.*
15
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Mr. Bowman opened the meeting and asked Dr. deTreville to conduct
the session on Asbestos. Dr. deTreville, who had asked several of those
present to be prepared to discuss their areas of special interest and research
needs, first called on Dr. George W. Wright to report briefly on his activities
of the past year in behalf of the Quebec Asbestos Mining Association (QAMA).
Dr. Wright said that he had been aware of industry's interest in asbestos
since about 1940, as a result of his work at Saranac Laboratory for QAMA. At
that time no question was raised concerning possible malignancy. At a meeting
in Antigua in 1965, QAMA expressed its intention to learn, "What is known,
what we need to know, and what is unknown" concerning the bioeffects of asbestos.
Concerning what is known, Dr. Wright listed the following scientists
who were present in Antigua:
Dr. John Beattie Cambridge, England
Dr. H. Bohlig Ludenscheid, W. Germany
Dr. John C. Gilson Penarth, Glamorgan, Wales
Dr. Roger Grainger Asbestos, Quebec
Dr. Paul Cartier Thetford Mines, Quebec
Dr. Fernand Gregoire Montreal, Quebec
Dr. A. Claass Luxembourg, Belgium
Dr. Paul Gross Pittsburgh, Pa.
Dr. L. J. Cralley Cincinnati, Ohio
Dr. A. J. deVilliers Ottawa, Ontario
Dr. Roland Guy Cartierville, Quebec
Prof. A. Houberechts Hasselt, Belgium
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Dr. J. C. McDonald Montreal, Quebec
Dr. Leo Noro Helsinki, Finland
Dr. Sherman S. Pinto Tacoma, Washington
Dr. Arthur J. Vorwald Detroit, Michigan
Dr. J. C, Wagner Penarth, Glamorgan, Wales
Dr. George W. Wright Cleveland, Ohio
Prof. Paul Sadoul Nancy, France
Dr, K. W,. Smith New York, New York
Dr. Philip Enterline Montreal,Quebec
Dr. Philippe Duval Noranda, Quebec
Dr. J. A. Vidal Montreal, Quebec
Dr, Eugene Pendergrass Philadelphia, Pa.
Prof. E. C. Vigliani Milan, Italy
Mr. K*. W. Nelson Salt Lake City, Utah
In the course of the QAMA Meeting, much of "what is known" was
reviewed and discussed. Dr. Wright found the meeting very valuable from
a personal standpoint, chiefly regarding discussions of the very pertinent
questions,'`What we need to know" and "what is unknown. "
For example, he stated that the word "asbestos" is as general a
term as "bacteria" and that it is not possible to translate data from one type
to another. The types vary with origin and chemical composition and almost
never exist in a "pure" form. It is very difficult to categorize an exposure
environment because of the need to capture, identify, recognize, and quantitate
the material we now call "asbestos". During processing, asbestos, which is
not indestructible, may undergo dissolution or change in form. Is the material
redisseminated identical to the original, or does it differ?
Dr. Wright indicated that it had been sobering to realize the extent
to which asbestos is distributed in various forms in the general population,
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4. and we must have better knowledge of where asbestos may come into contact with humans and better recognize any adverse bioeffects which may have resulted.
Dr. deTreville next asked if Dr. Kenneth W. Smith had any comments concerning the Asbestos Textile Institute program. Dr. Smith related that the Asbestos Textile Institute is cooperating in an extensive investiga tion with the asbestos textile industry by the U. S. Public Health Service under the direction of Dr. Lewis J. Cralley. The ATI has felt the impact of adverse criticism in the form of press releases, radio, and television appearances concerning asbestos. Aside from knowing the facts concerning the true effects of asbestos upon man, the industry must be increasingly concerned with preservation of its markets as a matter of survival. All the individual company can do to help solve this pressing problem is to provide funds, environments, and individuals for study.
The basic research needs will have to be "farmed out'1, but studies are already being conducted on insulation workers on the West Coast and in the Midwest. In Canada, Johns-Manville Company is studying all insula tion workers who have permits, and this study has government approval. The ATI, as mentioned, is cooperating in an extensive survey by the U. S. Public Health Service, Division of Occupational Health. The National Insulation Manufacturers Association is vitally interested in developing information to pass on to insulator employer groups.
As he has pointed out repeatedly. Dr. Smith feels that the primary need is better definition of asbestos exposure, especially important in epidemiological studies. What is an asbestos worker? hi this regard
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5. he said, the loose thinking concerning asbestos exposure was demonstrated recently in Pennsylvania when the occurrence o mesothelioma in a three* year old child was attributed to the father's working in industry under the union category of an asbestos worker. Actually, this union category title covers many individuals who have no occupational exposure to asbestos.
At this point Dr. deTreville called on Dr. Lewis J. Cralley to pro vide a brief report on U.S. Public Health Service, Division of Occupational Health plans.
Dr. Cralley stated that he would like to cover briefly three areas of U.S. Public Health Service, Division of Occupational Health interest.
(1) A prospective longitudinal epidemiological study is now under way in four industry exposure categories:
(a) Asbestos textiles (b) Asbestos friction products (c) Asbestos cement products (d) Asbestos insulating materials The aim is to cover at least 2500 workers in each category with a wide range of exposure from office to production worker and with built-in controls. Exposures are being defined in detail including factors other than asbestos. In addition, the past history of plants regarding asbestos exposure is being recorded in an attempt to develop retrospective studies designed to compli ment those of a prospective nature. Detailed information on each worker is being developed using a questionnaire approach, which includes occupations, hobbies, and smoking history. These studies will be carried out over the
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lifetime of these individuals whether or not they* stay in the industry. At inter
vals a follow-up will be made using Bureau of Old Age and Survivor's Insurance
records and State Department of Health death records from whicha trend of causes of death will be developed for each group. A designated number in each group will
have periodic medical follow-ups to establish health profiles. While the pro
spective study itself will require 25-30 years of workers* experience, it may be
possible to recognize trends as early as 5-10 years from the time of the base
line study.
(2) Concurrently, a study will be made of the lungs of individuals in
the cohorts who died of cancer. This will include complete mineral analysis
of trace metals including nickel, cobalt, chromium, etc. In this regard,
individuals will be categorized into two groups--those having significant
exposure before mid 1940 and those entering exposure after this period. Tech
nology has changed markedly since the 1930's, and contaminant fines of asbestos
have been reduced 30% or more. Exposure of workers is generally no longer
massive. Data collected should help provide insight in understanding past and
present worker health experience.
(3) The U. S. Public Health Service is also very interested In identi
fying the various types of pulmonary ferruginous bodies that have been observed
in a number of persons coming to autopsy in hospitals in urban areas. For
example, talc has been found to contain about 10% fibers. In veiw of the wide-
spread use of talc in cosmetics, etc., could some of the ferruginous bodies
be from this source? Also, just what does the presence of these bodies mean?
A U. S. Public Health Service records study begun by Dr. Philip Eater
line is designed to detect contrasting differences in trends in causes of death of
workers in different asbestos product cohorts. The importance of Knox's and
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vivor's Insurance
acha trend of causes of in each group will
While the prorience, it may be
ime of the base
f individuals in neral analysis is regard, ignificant s period. Tech: fines of asbestos 'ally no longer mdi*._ ^ast and
*sted in identire been observed treas. For iw of the widenous bodies : bodies mean? r. Philip Enterises of death of of Knox's and
7*
Doll's study is that early data indicates that industrial hygiene control of dust exposures will reduce the incidence of lung cancer in asbestos workers.
Dr. deTreville then requested Dr. Cross to provide a detailed des cription of IHF's Fibrous Dust Research Proposal.
Dr. Gross said that Thomson^) has found that about 30% of the people that had died in hospitals in Capetown (500 consecutive autopsies)
had "asbestos bodies" in the lungs. The same author^) had found a similar
prevalence of "asbestos bodies" among the hospital deaths in Miami, Florida. Cauna, Totten and Gross^^ examined the lungs of 100 non-selected hospital
deaths for which autopsy permission had been obtained and found that 40% of these had "asbestos bodies" in their lungs. Ian Webster^) recently reported a 47% prevalence in Johannesburg.
There is, at present, a reasonable doubt that "asbestos bodies" are specific indicators of the inhalation of asbestos fibers. Such bodies have been found in coal miners and talc workers where they have been called
(1) Thomson, J.G., et al. Asbestos as Modern Urban Hazard. S. Afr. Med. J. 37:77-81, 1963.
(2) Thomson, J. G., et al. Asbestos as an Urban Air Contaminant. Arch Pathol. 8J_:458-464, May 1966.
(3) Cauna, Dzidra; Totten, Robert S. ; and Gross, Paul. Asbestos Bodies in Human Lungs at Autopsy. JAMA 192:371-373, May 3, 1965.
(4) Webster, Ian. Report of progress quoted in the Annual Report of the Pneumoconiosis Research Unit of the South African Council for Scientific and Industrial Research, 1965.
s.
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8.
"pseudo-asbestos bodies.*1 Recently Davis ^ and Collet^ have demonstrated
the intracellular development of "asbestos bodies" secondary to amorphous material.
Asbestos occupies an anomalous position in its ability to produce lung damage, causing diffuse fibrosis and possibly also lung cancer. Xt is anoma lous inasmuch as no other silicate has been shown to possess this ability. The fibrosis encountered in talcosis is limited to the tremolite variety, which is asbestos-like. On the other hand, the pneumoconiosis associated with the mining of mica (another silicate) has not been investigated experimentally, and the fibrogenic activity of the dusts coexisting with the mica has not been evaluated. Other silicates may evoke either minimal or relatively slight inflammatory changes, and are incapable of producing lung cancer.
Inasmuch as certain polycyclic hydrocarbons and trace metals known to be potent cancer-producing agents have been demonstrated in asbestos, particularly nickel, chromium and benzopyrene, the possibility exists that the trace metals and/or the polycyclic hydrocarbons may be solely responsible for the observed pathogenicity.
This possibility is supported by two findings; 1. The report of Braun and Truan^ which indicated that the preva
lence of lung cancer among Canadian asbestos miners was no greater than that of the general population. This was in contrast to the report of Doll^ *
(5) Davis, J.M.G. Electron-Microscope Studies of Asbestosis in Man and Animals. Ann. N.Y. Acad. Scie. 132:98-111, 1965.
(6) Collet, A. Personal Communication, 1965. (?) Braun, Daniel C. and Truaa, T. David, An Epidemiological Study of
Lung Cancer in Asbestos Miners. AMA Arch. lad. Health 0:634-653, June 1958. (8) Doll, R. Mortality from Lung Cancer in Asbestos Workers. Brit. J
Ind. Health 12:81, 1955.
which it exposed to
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which indicated a greatly increased risk of lung cancer among British workers
exposed to asbestos dust while fabricating the asbestos.
2. In a recent investigation in the laboratory of the Industrial Hygiene
Foundation, lung cancers were found in rats exposed for 18 months to high
concentrations of chrysotile dust.
Because rats exposed to chrysotile dust
by other investigators failed to develop lung cancer, there is a good probability
that the chrysotile dust that produced lung cancer was significantly different
from that which did not have this effect. It is possible that this difference is
caused by a coating of nickel steel alloy applied to the asbestos dust particles
during the continuous hammer milling process used for rendering the dust
respirable. This method has not been used by previous investigators. Nickel
has been found capable of producing lung cancer in trace amounts.
Although asbestos and glass are both silicates, the industrial health
experience with workers of these two materials has been vastly different.
No pulmonary disease has been reported in workers exposed to glass dust.
Nevertheless, the dust of filamentous glass has been labeled as highly
dangerous in the lay press by association with asbestos. It is a fact that
although the effect of flake glass dust on the lungs of animals has been reported,
no similar study has been made of the dust of filamentous glass which does
not have an associated resin or fiUer.
It is proposed to examine the response of animals' lungs to different
inorganic fibrous materials of contrasting chemical composition, and to
characterize the differences and similarities in the response.
(9) Cross, P. and deTreville, R.T.P. Experimental Asbestosis: Studies on the Progressiveness of the Pulmonary Fibrosis Caused by Chrysotile Dust. To be published.
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10.
It is also proposed to investigate the influence of trace minerals and
polycyclic hydrocarbons (i.e. , benzopyrene) associated with chrysotiie ore
or the subsequent processing on the long-term response of the lung to the dust.
Another objective of this phase is to obtain definitive data on the long
term effect of dust derived from filamentous glass upon the lungs. Three
varieties of such glass dust wilt be investigated:
1. with the phenol-formaldehyde-type of binder 2. with the binders used in textiles 3. without binder
In addition, a comparative study of the three main types of asbestos
dust (chrysotiie, amosite and crocidolite) is proposed to attempt to pinpoint
the cause of biological activity-- i. e., whether due to silicates per se or the
associated trace metals or hydrocarbons. Positive findings would be a basis
for identifying any possible health hazards and for suggesting specific engineering or other process controls to eliminate such hazards.
1. The following fibrous materials will be reduced to respirable
particle size (<3|i) and will be injected in amounts of 3.S mg. to 30 mg. as
aqueous suspensions:
1. chrysotiie dust {prepared by milling in Wright mill and with demonstrated carcinogenic potential)
2. chrysotiie dust (unmilled synthetic)* 3. aluminum nitride 4. tricalcium phosphate (filamentous) 5. fibrous glass
a. with phenol-formaldehyde-type binder b. with binder used for textiles c. without binder 6. magnesium hydroxide (brucite) 7. mineral wool 8. zinc oxide (filamentous)
* Synthetic chrysotiie has been prepared at Mellon Institute by Dr. William Granquist. Electron photomicrographs show the characteristic tubular crystals.
Thest ether anesthesia, will form in reap therefore be helc sought in lung ju:
The lungs 10 cm. of water, after paraffin im methods and pho: completely the t: so-called asbest sections stained examined under ' when examined i
The diffe dust and thaC point to the cont trace substances result of process
The deve bodies, to dusts these structures from human lung
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These materials will be injected intratracheally into hamsters under ether anesthesia. Previous experience has demonstrated that asbestos bodies will form in response to chrysotile dust within five months. The animals will therefore be held for six months and then kilted. Asbestos bodies will be sought in lung juice as well as in. the lung tissues*
The lungs will be expanded with buffered formalin under a head of 10 cm* of water. Blocks removed from these lungs will be sectioned at 6 n after paraffin impregnation. These sections will be stained by different methods and photographed sequentially to provide means for studying more completely the tissue reaction to these various materials. Search for the so-called asbestos bodies will be made using routinely stained sections, and sections stained for iron. In addition, unstained cleared sections will be examined under dark-field conditions for asbestos bodies. The latter glow when examined in this manner.
The difference in tissue reaction between the synthetic chrysotile dust and that which is known to be fibrogenic as well as carcinogenic will point to the contribution to pathogenicity made by one or more of the various trace substances which may be associated with chrysotile asbestos dust as a result of processing.
The development of "asbestos bodies, " better termed Ferruginous bodies, to dusts other than asbestos would point to the non-specificty of these structures and to the desirability of collecting such "asbestos bodies" from human lungs in order to subject them to electron-probe analysis. Such
V.
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analysis could give information in regard to the chemical make-up of the dust
responsible for the development of the Ferruginous ("asbestos1') body.
II. In order to explore the etioiogic role of the various components of
chrysotile asbestos in the production of lung fibrosis and lung cancer, six
series of rats will be injected intratracheally with the following:
1. chrysotile dust known to be carcinogenic^) 2. synthetic chrysotile 3. synthetic chrysotile plus nickel 4. synthetic chrysotile plus chrome 5. synthetic chrysotile plus nickel, chrome and benzopyrene 6. nickel alone or with carbon as carrier 7. chrome alone or with carbon as carrier 8. benzopyrene with carbon as carrier.
These rats will be held for two years and then killed. The lungs will
be prepared for examination and sections cut in the same manner as in
Phase 1.
Three other series of rats wilL be injected intratracheally with the
following dusts:
1. filamentous glass with phenol-formaldehyde-type binder 2. filamentous glass with the binders used for textiles 3. filamentous glass without binder.
These animals will also be held for two years and then killed. The Lungs
will be prepared and studied as in the preceding groups, with special attention
to asbestos bodies in Iting tissues or juice.
The number of animals per series will be such that there will be
no doubt regarding the statistical significance of the results.
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III. Because of the interest of a number of companies in biologic investigations similar to those planned for chrysotile asbestos, but using instead, amosite and crocidolite, an additional investigation is proposed to be undertaken concurrently.
As in the proposal dealing with chrysotile asbestos, the purpose of this supplemental, concurrent investigation is to attempt to pinpoint the cause of the biologic activity of all three main types of asbestos dusts; whether this lies in the silicates per se, in the associated trace metals, or in the associated hydrocarbons.
Because neither amosite nor crocidolite is available as a pure synthetic material, the investigation proposed for these two types of asbestos is necessarily different from that proposed for chrysotile. Nevertheless, in order to make the investigation complete, it is desirable to include also chrysotile in the new investigation since different methods are involved.
A Inasmuch as the biologic activity of asbestos seems to have two components: (a) inflammatory--responsible for asbestosis, and (b) neo plastic-- responsible for lung cancer and mesothelioma, it is advisable to investigate both of them. This can readily be accomplished within the four year span contemplated for this investigation.
In order to determine whether the biologic activity of asbestos resides in the silicate, in the associated trace metals, or in the associated hydrocarbons, attempts will be made to remove the trace metals and the hydrocarbons from their respective silicates and to compare the biologic activities of such "purified11 asbestos samples from which these associated materials have been removed.
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14.
As a prerequisite to any biologic testing (insofar as the lungs are
concerned), it is necessary to reduce the asbestos to a respirable particle
size. This will be done in the following manner; the amosite and crocido-
litc will be ball-milled and then fed into continuous hammer mills modified
from a design by Holt and Young.
The dusts emerging from the hammer
mills will be collected in electrostatic precipitators. This method has been
used successfully by us to reduce chrysotile asbestos to a particle size,
70fo of which was respirable. A sufficient quantity of finely divided chryso
tile dust is available for the purposes of this investigation.
All three types of asbestos dust will be deprived of the greater
portion or of all of their hydrocarbon content in one of two ways:
1. by continuous extraction with various solvents 2. by heating beyond the decomposition point of the
hydrocarbons
The trace metals will be removed from the three types of asbestos
dust by treatment with aqua regia followed by treatment with EDTA (ethylene
diamine tetraacetic acid, a chelating agent).
One batch of each type of asbestos dust will be subjected to both
procedures, i.e., removal of trace metals and removal of hydrocarbons.
Accordingly, each of the three types of asbestos dust will consist of
five batches, each with a different composition:
1. the unaltered dust as collected in the precipitators 2. the dust minus the hydrocarbons (heat-treated). Here,
it is anticipated that there may also have been some change in the chemical structure of the asbestos through loss of some molecules of water of hydration.
(10) Holt, P.S. and Young, D.K. A Dust-Feed Mechanism Suitable for
Fibrous Dust. Ann. Occ. Hyg. _2:245, I960.
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it is anticipated that the extraction may not be 100% complete. 4. the dust minus trace metals 5. the dust minus trace metals then subjected to solvent extraction
to remove most of the hydrocarbons Zn order to investigate the inflammatory component of the various (15) batches of asbestos dust, these will be injected intratracheally into rats and hamsters. The lungs of these animals are expected to show definitive changes within one year after the intrapulmonary introduction of the dusts. In order to explore the lung cancer aspect of the neoplastic com ponent of the biologic activity of asbestos dust, additional rats will be injected with the same batches of dust as above and allowed to live out their lives. Most of the animals, however, will have died before the end of the third year. The other (mesotheliomatous) aspect of the above neoplastic com ponent will be investigated by injecting the 15 different batches of asbestos dust within the pleural cavity of rats and hamsters and allowing them to live out their lives. Most of these animals will also have died before the end of the third year. For the investigation of the inflammatory component of asbestos dust, a large enough number of animals will be put on test to allow sampling at intervals throughout the year and still have an adequate number remain ing to represent the 12 month old lesion. The final report covering the entire investigation will be issued toward the end of the fourth year. This report will probably be in the form of several manuscripts suitable for publication.
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K 16. In the discussion which followed. Dr. Dee B. Grant asked if chrysotile asbestos was soluble in acid and Dr. Gross replied affirmatively, indicating about 5% in 8 hours. Dr. deTreville inquired concerning the status of support which the U. S. Public Health Service has developed through congressional appropria tion. Dr. Craltey indicated that the present budget was very minimal but there was hopeful indication that increased support in the future would permit research of a higher level of effort. Dr. deTreville asked concerning the status of the extension of the IHF's five-year epidemiological study reported by Braun and Truan in 1958. Dr. Wright said this was one of the areas under consideration within QAMA. In answer to Dr. deTreville's question regarding possible areas of IHF-QAMA coordination. Dr. Wright indicated that he would certainly be interested in assistance in funding any projects recommended by the Scientific Council which could not be funded by the Administrative Council of QAMA. There being no further discussion. Dr. deTreville indicated that a report of the minutes of this session would be prepared. There was no objection or further discussion and the Chairman asked Dr. deTreville to perform such follow-up as seemed appropriate to carry out the intent of the meeting, as previously stated in the purpose.
Note: At a meeting of the Foundation's Board of Trustees on October 18, 1966, approval was given to publish these minutes for the benefit of the Founda tion's membership and that an information copy be sent to the U. S. Public Health Service Surgeon General.
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