Document OzVEjR1dg8x49mEED51E48n4v
ST0095765
f Reprinted from Biological tfftctt of Aihcstos, 1973, Lyon, International A*ency for Research on Cancer, pp. 238-212
Are ferruginous bodies an indication of atmospheric pollution by asbestos?
J. M. G. DAVIS & P. GROSS
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Are ferruginous bodies an indication of atmospheric pollution by asbestos?
i J. M. G. DAVfS 1 4 P. GROSS *
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The discovery that there was an association from the community in question and not with air between asbestos inhalation and the occurrence of from other sources or locations.
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mesotheliomas led to the first detailed studies on
atmospheric pollution by asbestos. Since- it ap
peared that very short exposures to asbestos in low
THE SPECIFICITY OF FERRUGINOUS BODIES
concentrations could produce these tumours, it was
suggested that the use of asbestos-containing goods, Ferruginous bodies are composed of iron-contain
from ironing boards to brake-linings, might be caus ing protein and apatite deposited upon and around
ing sufficient atmospheric pollution to endanger inhaled or injected particles of microscopic dimen
(1 members of an urban population. In order to test sions. The common feature as seen optically is the
this hypothesis, groups in different parts of the world colour of the ferruginous bodies, ranging from pal-
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examined lung tissue from autopsy specimens taken straw to deep gold to red brown, contributed by their
at random; ho-.vever. since uncon ted asbestos dust is iron content; and they therefore stain deep blue for
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extremely difficult to detect in tissues by normal light iron with acidified potassium ferrocyanide. De microscope methods, a count of asbesto*- bodies was pending upon the shape of the particle which forms
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used as an- index of asbestos contamination. As its nucleus, these bodies may be elongated, rounded,
I methods of tissue examination became more critical, ovoid or irregular. The nucleating particles may
an increased percentage of lungs was found to con consist of fibres, such as those of asbestc-s, glass or
tain bodies; and reports ranged from that of mineral wool, or of nonfibrous material (Gross ct a!.,
Thompson ct at. (1963) in Capetown, who found 1968; Davis ct at.. 1970); and these particles may be
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bodies In ultimo to* ,, of it ser i.-s ofltinns, In the find optically transparent or opaque. It is. therefore, ings of Gross ct nl. (19691 who reported that 97; , of obvious that, from a theoretle.il point of view, fer
lungs from a Pittsburgh series contained bodies.
ruginous bodies arc not specific indicators of asbes
However, it soon became obvious that ferruginous tos.
bodies could only be used a* an index of the degree Whether, from a practical point of view, a su'Tt-
of atmospheric pollution by asbestos in a given com cicntly large percentage of ferruginous bodies found
munity providing the following criteria were met, i.c., in the lungs of persons not occupationally exposed to
that;
asbestos are nucleated by asbestos fibres to allow on
to ignore those ferruginous bodies nucleated h>
(1) ferruginous bodies are specific for asbestos; (2) a quantitative relation exists between ferru ginous bodies and asbestos fibres; and (3) the ferruginous bodies found in a lung arc nudepted only by asbestos fibres inhaled with air
fibres other than those of asbestos has not been de termined. Some studies on this problem have been published, hut the results arc conflicting. Thus Gross ct at. (1969) examined ferruginous bodies from IS cases and concluded that none contained chi><o-
* Institute of Ov.'-'i'i'.ittoiul \tiM:kine, rdinburaS. UK. Dffvirimcnf of >\:l <!<vcr:i> of South Clfolmj, Cl.arkxtvin, South Cjroluu, USA.
tile asbestos. However, Larger ct al. (19701 repined that chrjsotile was present in most of the ferrugnvai bodies found in a scries of cases they examined from
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au ferruginous booies an indication of atmospheric pollution by asbestos?
239
New York City. More attempts to establish the asbestos loud in the lungs of urban dwellers were made by Pooley et a! (1970) and Lnnger </<7/. (1971): the latter reported that chrysotilc was present in 24 out of 28 cases from New York City, and Pooley and his colleagues found chrysotilc in 70% of a scries of cases in London. These studies were, however, not quantitative and could not clarify the relationship between uncoatcd fibres and ferruginous bodies.
a quantitative relation between ferruginous
BODIES AND ASDI STOS IN THE LUNGS
In order to evaluate this criterion, meaningful quantitative methods based on adequate sampling of dry lung tissue bv weight (10 g or more) must be employed. Methods based on the examination of only one or even of several blocks of lung tissue arc inherently inaccurate and may lac misleading, since the state of distension of the lung tissue ts variable, and because the sampling is inadequate in terms of the total lung volume.
Method
By digesting a known weight of dry lung tisjue with sodium hypochlorite, all ferruginous bodies and mineral fibres arc set free. These are washed and suspended in specific volumes of water, usually so that I ml of suspension is equivalent to I g of dry lung tissue. Measured amounts arc placed on cover slips, dried, and then fixed; and counts are made of the ferruginous bodies and fibres. Simple calcula tions convert the counts into numbers of ferruginous bodies and fibres per gram of dry lung.
Recently, this method has been adapted for enu merating submicronic fibres. The adaptation con sists of adding a known number of latex spheres to a known volume of standardised lung-sediment sus pension. A droplet of this mixture is allowed lo dry on an electron microscope grid. All fibres and fibrils, as well as latex spheres, are counted on each grid, and these data arc similarly converted into fibres per gram of Jry lung.
Using this electron microscope technique, fibres have been grouped into three categories: those fibres over 5 jim in length; those fibres less than 5 |im in length; and those fibres which, from their general
TeNe 1. Oust end ff*rruflinou* body count* from people not industrially ntpos*d to ethetfot
Fibres* viable
s Age Total duir4
with light
microscope
F 71 F 7? t 78 F 45 F 60 M 77 M 89 M 59
M 62 F 25 FO M 61 F 40 M 55 F 70 F 79 M 70 M 62 f 48 r 39
Avvrte*
85
66
26 65 '0 33 16
10 9
05 42 06 74 08 oe 30 17 07 04 93 05
26
6.000 53.000 34.000
8.000 20.000 49,000 170.000
8 7,COO
53.400
2.700 48.800
2.800 4.400
700 900 1 800 800 900 BOO 400 500
5.600
Ferruginous bodies*
153 90
309 258
53 60 392 ni
178
1.020 31.500
103 51 59 27
188 357 400 160 140
--
3.090 (250)
Fibres vmblt m ek :tron microscop*'
over S urn
below 5 um
Similar to cbrysoti'e
1940
575 154
220
630 97
318 235
4810 683
875 635 755 373 778 963
800 70 O 35 oc 65 60 lA 27 t
187 a.
39
522
1234
ISO
220 1950
140 120 716 157 140 1C5
58 890
47 57
550 4850 '
700 380 1083 555 ` 306
535 311 1671
108
110
55 1100
55 40 74
23 21 47
6
104
7
9
%* <
389 913 128
Total dutt it nr'C.'i'rf at m-c.qr.iTis of
rer cam of df'C * V-'l
% FeuC'f>0u* T-iM ` *.ve% run't >'h the rv^c scope a*e uni s*ed
M<u*
nufrvfAfound per pram ol dried Igng
f f .txvs vs<Ne Or'v * t*' iVctro n microscope e*prens*d I'P'es per miM.g#,im of dried tun t>Mwt.
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ST0095769
AM FERRUGINOUS BODIES AN INDICATION Of atmosthuuc pollution by asbestos?
241
appearance, look like chrysotile (Figs. 1-41. The structure of chrysolite as seen in the electron micro scope is characteristic; but such recognition cannot be considered completely diagnostic, and specific characterisation of the chrysotilc fibres is therefore necessary. This is possible with electron diffraction techniques, but the process is too time-consuming to be used on ail fibres that look like chrysolite. Several hundred electron diffraction patterns arc, however, being collected from a random series of such fibres, and the analysis of the patterns should give an indication of the percentage of the counts that represent true chrysolite.
lung. Fibres similar to chrysotile were therefore found in all the cases examined, but they made up only a smalt percentage of the total mineral fibre. The highest percentage found was 17, but the average was only 9*/,.
One can, therefore, draw the preliminary conclu sion that there is no quantitative relation between the number of ferruginous bodies and the number of fibres, whether optically visible, submicronic. or those similar to chrysotile. Occasionally, we have examined lungs of people living in scacoast com munities relatively free of industrial pollution in which there were high fibre counts but in which few ferruginous bodies have been found.
Results
Studies were undertaken on the lungs of members of a normal urban population in both Pittsburgh, Pennsylvania and Charleston. South Carolina who had had no known industrial exposure to asbestos. Although the number of lungs on which optical counts, as well as electron microscope counts, base been completed is not large, the range of values obtained far both optical and submicronic fibres, as well as for ferruginous bodies, is extremely w ide. In light microscope studies it has been found that the total number of mineral fibres in the lungs examined ranged between 15,000 and 400,000 per gmm of dried lung. It has also been found that the fibre content of the lungs bears no constant relationship to the total
FERRUGINOUS BODIES IN A LUNG NUCLEATED BY ASBESTOS riBRtS CARRIED BY THE COMMUNITY IN QUESTION
This criterion could pci haps be satisfied in isolated, small, stable communities in which the inhabitants are immobile. Since such communities arc few in industrialised nations, there would be xery few re gions in which the ferruginous bodies in the lungs of the residents could serve as an index of atmospheric pollution by asbestos, even if the other two criteria could be met.
lung dust content; some specimens with a very high
total dust content contain relatively few fibres. The number of ferruginous bodies present in the lungs has been found to range between 28 and 4000 per gram of dried lung tissue, and the ratio of ferruginous bodies to uncoated fibres has ranged between 5 : and 11,000:1.
In electron microscope examination of the dust
The answer
Thus, the answer to the question as given in the title of this paper is that ferruginous bodies do not qualify as an index of atmospheric pollution by asbestos, for the following reasons:
(1) Ferruginous bodies arc not specific for asbes tos.
samples the following figures have been obtained (2) There is no quantitative'relation between the (Table I); the number of fibres more than 5 :im long number of ferruginous bodies and the number of
ranges! between 47 and 1950 per milligram of dried asbestos fibres in a lung.
lung; the number of fibres under 5 urn in length ranged between 106 and 4810 per milligram of dried lung; w hile the number that looked like ehry so tile ranged between 7 and 1100 per milligram of dried
(3) The mobility of people in industrialised com munities precludes the likelihood that ferruginous bodies found in a lung are nucleated by fibres in haled in only one community.
Figs. 1-4. fteetron-microseone photo<ir*ph* ol mineral Lares isolated (ram the tunrjs of human* not industrially exposed to asbestos. In each ease the Lino consul* of a bune'e of cxjta's cf * *-- 'ai Oiamctcr fo ft cse of chrysotile. jnd the brcen
end of the fibre shows that the crystal* break luerju'arfy m a senes of steps. In each case some of the crystals show the
tubular structure that it characteristic of chrysolite (arrowed).
Mtgmficsiiont: F.g. 1 12.599--Figs. 2-4 * 45,000
ST 0095770
242 MOLOGIOU. EFTTCTS Of ASBESTOS
OOMVTVTS
Largely because of this answer, we base concen trated our attention on examination of the uncoated or naked fibres in lung tissue. One of the more signi ficant aspects of our findings is that a sizeable per centage of the fibres found in the lungs of adults are less than 5 pm long and, on the average, about 10% of these short fibres can probably be identified as chrysotile. This, of course, docs not necessarily classify the other 90% of short fibres as non-asbestos.
Short crocidolitc asbestos fibres less than 5 urn long were found by Webster (1970) to be non-fibrogenic. Hilscher et at. (1970) came to a similar con clusion, not only with short crocidolite, but also wiih short chrysotile fibres. In our own studies, the pre liminary results of an experiment in which 2-1 me of short-fibred chrysotile was injected intratracheally showed not only that this large amount of asbestos was well tolerated by the animals, but that the tissue response was a macrophage reaction without signi ficant stromal proliferation. This is i.i contrast to experience with intratracheal injections of longfibred asbestos, w here doses greater than 2 mg were regularly associated with mortality, and where a fibrosing tissue response was later demonstrable in surviving animals.
Another pertinent observation with regard to
short-fibred asbestos was made several years ago during studies of ferruginous body formation (Das is. 1970). It was found that fibres which could be com pletely ingested by macrophages, i.e., those shorter than 5 urn. did not become coated with ferruginous material.
Thus, a degree of uncertainty exists with regard to the health hazard posed by asbestos fibres shorter than 5 um long. This uncertainty is reinforced by a failure to associate specific pulmonary disease v. iih the presence of asbestos dust in the lungs of people not occupationally exposed to (his dust. The wide range of loads of asbestos dust encountered in such subjects, where there is no evidence of specific pul monary disease, suggests that there is a dose-response relaii. isnip and that the level at which there is a demonstrable response has not been reached in those examined.
It is obviously necessary to determine at what level of asbestos dust in human lungs the earliest fibrogenic response can be demonstrated; this determina tion so far appears to be feasible only for people who have a history of occupational exposure to asbestos.
It is even more important to determine whether the carcinogenic elTect of asbestos is also dose related, and at what level of atmospheric contamination a danger of tumour formation is fou.id. So far there arc no data on this subject.
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Davis, J. M. (1970) Further observations on the ultra structure and chemistry of the formation of asbestos bodies. Experimental and Molecular Pathology, 13, 346-358
Davis, J. M. G.. Gross, P. A D Trcville. R. T. P. (19701 Ferruginous bodies in guinea-pigs. Archives of Patho
logy. *9, 364-373 Gross, P., De Trcville, R. T. P., Cralley, L. T. A Davis. }. M. G. (1968) Pulmonary ferruginous bodies.
Archives of Pathology, 85, 5.19-546 Gross, P.. De Tresille. R. T. P. A Haller, M. V (196))
Pulmonary ferruginous bodies in city dwellers. A study of their central fibre. Archives of Enr ironmvntal Health, 19. lRfi-IXS Hilscher, \V,, Scihi, S., Friedrichs, K.-II. A Pott, F.
(19(0) Zus.imnienhanp.c /wischcn A-besto-.' unJ FaserUnge. Die \tutr > inriniIwltcn, ?7. tyr, .'.xe Inngei, A M , Rid'in, t A' Xchkotl, I 119 01 ^\\*.roriinuuipiotij aiulvM> ol ails iio. n> .1.. . In. Xl.ui'ii.i, H. A., eu.. rm, r.'i'rt'mjiii. I'r.'t. t ilings of ihe Inter
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hth f HtihUUrtt t
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