Document ZJwzE4k0DDZOVoZbKb518K7q7
MMMF Research Update
A Case-Control Study of Malignant and Non-Malignant Respiratory" Disease Among Employees of a Fibreglass Manufacturing Facility
Chiazze. L. et a!. British journal of Industrial Medicine, eh. 1992.
A case-controi study conducted on workers of a fibreglass pi ant has concluded to a sta tistically significant increase in respiratory cancer. The results or this study have been reevaluated to include non-workplace fac tors. such as cigarette smoking. Results of the interview portion of the case-control study clearly indicate that smoking is the most important non-workplace factor for risk of lung cancer in this group of workers.
Lung Function in Insulation Workers
Clausen.].. Xetterstrom. B. & Wolff. C.. British Journal of Industrial Medicine. 1993:50:252-256.
To evaluate the effects of working with modern insulation materials (rock and glass Wooh tne members of the Copenhagen Inion of insulation Workers were invited to participate in a study based on a health examination that included lung function tests such as forced vital capacity (FYC) and rorced expiratory vol ume in one second (FEV;). No differences in FVC were observed between the experi mental and controi groups, but insulation workers were found to have significantly lower FEVi values, independent of smoking.
In addition, a foiiow-up of workers who had participated in a similar study six years ear lier found that the decline in FVC for insu lation workers who smoked was significant ly greater than for smokers front tit^control group, in the present study, the decline in FEV] was sieniiicar.tiv higher for insulation
workers, independent o: smoking habits.
| Reading ListSelf-assessed termer exposure to asbestos
was not associated with iung function in
insulation workers.
| Health Risks from Exposure to
| Mineral Fibres: An
| International Perspective
The study concludes that working with
modem" insulation materials is associated | Edited by G.Gibbs. I. uunmeum M. Kido &
| T. Higashi. Captus University Press. 1993 with increased risk of developing obstructive
ii
lung disease.
A timely contribution from international 1
experts in the field of health-related effects 1
Environment
of mineral fibres: Papers presented at the j International Symposium on the Health j
Canada and Health
Effects of Low Exposure to Fibrous i Materials (Kitakyusnu. Japan: Nov..l99D :
and Welfare Canada | represent an updated overview of the cur- , | rent assessment of health errects of miner- :
Conduct a Study on
al fibres in both the occupational and : general environment. The report of the
the Potential Adverse
workshop on biological indicators repre- ' sents an in depth evaluation of modern
Effects of Man-Made Mineral Fibres
practices in health monitonng. Thesatel-
lite symposium introduces the reader to ;
jcurrent studies on mineral fibres in Japan
and other Asian countries
|
Mineral fibres are on Canada's Environmental Protection Act's priority list. All substances that appear on this list must be assessed to determine whether they are toxic, as defined in Section 11 of the Act
The Effects of an Environmental Controversy on Industry: The Asbestos Experience
ECODECISION. March
(i.e. whether exposure to these substances Each year, growing duo::; awareness of
causes harm to human health or the envi the environment creates scientific contro
ronment).
! versies that can have me or impacts on
j the business activities or many industries.
The first par; of this Federal Government
The analysis presentee snows that the
effects on business deper.c much more on study will evaluate exposure to these sub- \
stances in Canada, in order to develop a j the fierceness of the controversy than on
the regulations that are ultimately imple
profile of MMMF use. Environment Canada j mented. The experience :: the asbestos
has commissioned an industry survey to | industry is cited as an example of how an
obtain information on the amounts of these | environmental controvers-' can open the
materials, which are produced in. imported j door to scientific-inexactitude and arouse
to and exported from Canada.
Source: Thermal Insulation Association of Canada. TIAC Times. March 1995
i strong public opinion trem the outset. A i frequent consequence is mat too much
! attention is given to some problems to the i detriment of others, ieacrr.i to a wasteful
use of resources. Final/. environmental
We have moved...
Our new otiices are iocatec a: 1002 Sherbrooke St. West. Suite 1"0. Montreal. Quebec. Canada.
H.3A 3L6. Our phone and fax numbers have
rr'^^'fisd lfie 52;"-
controversy raises socie~ ; ' implicit eco logical standards''. For industries, prevent ing such controversies / ensuring that their products meet these standards has become a necessir-
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Idepliop.c- iM-ii ''-ho-'
6 THE ASBESTOS
Suit-- /1 Mnmrea. ouehet*
Telex: nss-MiV* iIXSTa:
Zr ' ' INSTITUTE
'leieaiPi-.-: '!-'
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HWBUI0013192
Carcinogenicity...
:md it has now become clear that there are vast differences among various respirable fibres presently used in industry. At the 1992 WHO/IARC (Lyon) Symposium on Biopersistence of Respirable Synthetic Fibres and Minerals, there was a strong consensus that there appears to be a continuum of val ues for biopersistence ranging from very short persistence (low durability) to practi cally indefinite persistence (very high dura bility) among the various respirable materi als tested.
(broken down'. .Animal studies from the institute of Occupational Medicine in Edinburgh showed that chrysotile asbestos and the glass fibres tested were cleared at approximate;'.' the same rate, whereas there was very kttie clearance of crocidolite asbesros.
with tire various forms of asbestos, different man-made mineral fibres vary' greatly in each of the three D parameters discussed. A sound regulatory policy must recognize the existence of a continuum of pathological potential for all respirable fibres, natural and man-made and establish exposure standards predicated on this continuum.
Current research points to a continuum in the durability of both natural and man made mineral fibres
Both in vivo (animal studies) and in vitro (biological fluid simulation) research have been conducted to evaluate the biopersis tence of different inhalable fibres. It has been demonstrated that for asbestos fibres. chrysotile has low durability' and short per sistence, while amphiboles are highly durable and persistent. While chrysotile is Cleared within weeks or a few months, it is recognized that amphiboles. in particular crocidolite and amosite have clearance half-times in the range of decades.
For man-made mineral fibres (MMMF). data has shown wide variability in the biop ersistence and solubility of different fibres, depending on their respective manufactur ing process and chemical composition. For example, glass fibres with high aluminum (Ai) content were shown to be more durable than those with low Al content.
A major German study undertaken by scien tists at the Fraunhofer Institute in Hanover compared a whole series of MMMFs (from glass to RCFs) and natural fibres form vivo durability. Half times for fibre elimination from the lung ranged from 10 to 500 days. Another study on durability from the 1.5. reported that inhaled RCFs showed no chemical alterations two years following end of exposure, whereas glass fibres snowed that some components had leached
CROCIDOUTS ASBESTOS
REFRACTORY CERAUC FIBRES
(HIGH Al OXIDE **<
:LOW A) OXIDE %)
mmmmmmmmmmmmmmmmm
AMOSHE ASBESTOS
VERY HIGH DURABILITY
CHRYSOTILE ASBESTOS
(HIGHAJ%`
MHH
GLASS
&OWAI%) W--mm
SLAG
All fibres are not created equal
Today, scientists view the three P's (dose, aimension and durability) as interactive and interdependent. Moreover, as with durability the parameters of dose and dimension exist on a continuum of patho genic potential. At low doses, many fibres produce no detectable health effects. All other things being equal, as the dose increases so too will the potential health risks. Similarly, fibres which are less than 5um in length can be easily eliminated by the body's natural defense mechanisms. Fibres of 10. 20 or 30um and longer are increasingly likelv to escape macrophage elimination ana remain in the lungs.
In addition to the scientific ramifications of this avenue or study, there can be practical and regulator.' implications as well. increasingly, regulations will have to focus on note cnaracteristics and descriptions ratner man : r mineral or trade names. As
References:
Churg. A.. Lung. Asbestos Content in Long term Residents of a Chrysotile Mining Toivn. Amer. Rev. Resp. Dis.. 1986. 134( 1): 125-12"
Davis. IMG et al. The Pathogenicity ofLong Is Short Fibre Samples ofAmosite Asbestos Administered to Rats by inhalation and lntrapentoneal injection. Brit. I. Exp. Pathol.. 1986. 6":-i 15430.
Moali. P.A.. Macdonald..I.L.. and Kane. A.B. (198~). Acute injury and regeneration of the mesothelium m response to asbestos fibres. Amer. .1. of Path. 128 (31: 426-45.
Newhouse. M.L. & Sullivan. K.R.. A Mortality Study of Workers Manufacturing Friction Materials: 1941-1080. Brit. I. Ind. Med.. 1989. 36(31: 1_6-179.
Ohlson. C.G. and Hogstedt. C.. Lung Cancer Among Asbestos Cement Workers: A Swedish Cohort Study and Review. Brit. I. Ind. Med.. 1985. -t2(0>: 39^-t02.
Thomas. H.F.. Benjamin. I T.. Elwood. P.C. & Sweetman. PM. Further Follow-up Study of Workers from an Asbestos Cement Factori\ Brit. I. ind. Med.. 1982. 39(31: 2"3-2-6.
Wright. GW. & Kuschnen. M. Ti)e Influence of 1 drying Lengths of Class and Asbestos Fibres on Tissue Response m Guinea Pigs. Proceedings of the International Symposium of the British Occ Hvg. society. Edinburgh. >cptemDcr. 1 *9--^ -oS-i" :
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HWBUI0013193
Environment...
The Health
Asbestos-containing materials
contribute little to environmental
i Effects offibre levels
Several studies have examined the effects of
I Low Levels ofweathering on asbestos-cement products.
Meyer (1986) concluded that tire increase in
| Chrysotileasbestos fibre concentrations in the near vicini
ty of asbestos-cement cladding and roofing
material caused by weathering is so small that it moves into the range below the limit of detection of SEM. In a similar study of emis sion measurements. Borneman and Hildebrandt (1986) found that airborne asbestos levels were significantly lower than 0.001 f/cc. In 1991. the Western Australia Department of Occupational Health. Safety' and Welfare conducted an extensive review of environmental asbestos. The final report was comprised of school surveys, measurement studies and a literature review of the topic. The report found, based on air monitoring data gathered around schools with asbestos-cement roofs, that concentrations are unlikely to exceed 0.002 f/cc and are more likely to be less than 0.0002 f/cc.
[Exposure
i
i: The October 1992/January 1993 edition : of The Asbestos Institute Newsletter ' published as its lead story, a summary | and analysis of the preliminary results i of a landmark study of the health
i effects of exposure to chrysotile. The | study was of 5,351 Quebec asbestos | workers born 1891-1920 who had sur! vived into 1976. It was conducted by | Drs. ED.K. Liddell, A.D. McDonald and ! J.C. McDonald who found that "In each
i of six classes of exposure up to 300
I mpcf x years, the lung cancer SMR
Most narticles released into the environment are innocuous short
fibres
! [Standard Mortality Ratio = observed mortality/expected mortality] was ciose
: to 1.3 (a total of 25^ cases of lung can-
: cer among 4,384 men. against 190.6
In addition to the fact that environmental con expected.); there w'as no evidence of a
centrations have been round to be exceedingly trend." (Abstract presented at the 9th
low. other data shows those fibres detected are
International
Svmposium
of
likely to be short Chatfield (1983) reported to ; Epidemiology in Occupational Health.
a Government of Sweden Symposium, that ; Cincinnati, 1992). between 95 to 98% of fibres observed were
shorter than 5|Jm. The 1984 Report of the Royal Commission on Matters ofHealth and Sat'efy Arising From the Use ofAsbestos in Ontario published similar findings. In its review of environmental asbestos, it noted the prevalence of very short fibres and low counts t a maximum of 0.008-t f/cc of all lengths).
The authors have expressed concern to us that the article's subtitle "Important study finds that at exposure levels below a threshold of 50 f/cc. chrysotile asbestos is not linked to any increased incidence of lung cancer" could lead to misun derstanding. The notion of a threshold
References available from The Asbestos Institute.
was entirely our interpretation and not a direct quote of anv of the authors or tiie studv's abstract, which made no
mention of such a concept. We wish to add that our use of the threshold con cept was not meant to refer to a level below which the exposure risk is zero, since this cannot be proven with absolute certainty. However, it did refer to a ievel of exposure below which excess risk is not statistically signifi cant.
At the conclusion of the presentation of the study's preliminary report. Dr. J.C. McDonald noted that 300 mpcf x years could be regarded as approximately equivalent to 1.000 fibre years: which could have been accumulated over 20 years at about 50 f/cc. He concluded that "The significance of this study is that any deaths from asbestosis or lung cancer arising from current occupa tional exposure levels are most unlike ly-"
In publicizing Dr. McDonald's com ments and the findings of the prelimi nary report. The Asbestos Institute is in no way endorsing relaxed chrysotile occupational exposure iimits. The group of experts convened by the WHO in 1989 recommended mat chrysotile exposures should not exceed 1 f/cc. This has been and continues to be the level which we urge producers and users to meet. To believe otherwise would clearly be a distortion or the Institute's position. In fact, since its inception. The .Asbestos Institute has been dedicat ed to actively promoting, through close to one hundred training seminars and
information sessions in more than 60
countries, the application of interna
tionally accepted safe exDOSure limits
and work place practices. The Asbestos Institute has never suggested that this, or any other study is an invitation to reiax standards, but rather that it sup ports our view that current exposure
limits are realistic ana acceptable.
F
HWBUI0013194
T FEBRUARY/MAY 199?
THE ASBESTOS INSTITUTE
$s$es-n s i b Hte-><mi *~a sn <a e m >e n -t o f -:a vn rciftyu^'-a l r+e.*&io -m-rrxcve
Towards an Understanding of the Carcinogenicity of Fibrous Materials
The last decade has seen great advances in scientific understanding of the carcino-
genic potential of some fibres. Recent studies of fibre dimensions, durability and
dose-response relationships are helping to explain why some fibres, such as -
chrysotile asbestos are considered safe at low levels of exposure.
Twenty years ago. scientists had no clear understanding oi the mechanisms of the carcinogenicity of fibrous materials. The principal parameter studied was fibre dimension, and the nature of the correla tion between the length and width of a fibre and its carcinogenicity. It became clear from research programs of this nature that, although dimensions could explain some of the variations in the carcinogenic potential of different fibres, other factors were also involved.
With increased sophistication in analytical methods, scientists discovered that in addi tion to vast differences in fibre dimensions, there were also large variations in the dura bility of different fibres. The structure of some fibres were such that they could be cleared by the body's natural defense mech anisms more quickly than others.
Over the last 10 to 15 years, the concept of durability or biopersistence has plaved an increasingly important role in our under-
standing of the carcinogenicity of fibrous materials. Today, scientists are evaluating carcinogenicity of fibrous materials as an interaction between dose, dimension and durability or bio-persistence.
The dose makes the poison
In the 16th century, the Swiss physician Paracelsius wrote that aii substances can be toxic. The difference between the remedy
(see Carcinowncity on page 4)
Inside
Asbestos Fibres in the General Environment
Health Effects of Low Levels of Chrysotile Exposure
Changes Required to Fibre Research Methodology
MMMF Research Update
Environment Canada Study
Reading List
Studies find extremely low concentrations of mostly short asbestos fibres in the general environment.
A number of studies have been conducted in recent yeais to respond to concerns over what health risks, it' any. arise from asbestos emis sions in the general environment. Air sam pling was conducted in various rural and urban environments as well as in the vicinity of asbestos-contajning materials. Three major conclusions have emerged from this avenue of study.
Asbestos occurs naturally in the environment
The vast majority of asbestos fibres in the envi ronment (air. soil, water. e:;.i are the result of natural phenomena suer, as erosion. In facl_ asbestos was present in tne environment in similar quantities ion^_~-~ Te it was mined and used commercial!.
<see bnr.rument on page 2)
i
j
a ?
1 HWBUI0013195
Carcinogenicity...
and tiie poison ties in the amount: thus lire often-cited expression "the dose makes the poison . A tew centuries later, the issue n: low-dose risk remains a hotly debated topic in the scientific community. Although the techniques, models and jargon have changed, the controversy essentially revolves around the same basic question: "Is some thing that is toxic at high doses necessarily toxic at much lower doses?" Elegant theo retical models of toxicity and carcinogenici ty are presented in response to this question, and yet in some respects we are no closer to a conclusive answer. The principal point of contention centers around the possibility that even though no health effects may be observed, it is possible that these effects exist, but are undetectable using current data and methodology.
Some scientists maintain that for the pur poses of regulatory policy, the weight of ani mal and human epidemiological evidence is more important than theoretical postula tions. In the case of chrvsotile asbestos. there is a large bodv of evidence that demonstrates that at low levels of exposure, tile carcinogenicity is zero or undetectable low. The research ot Churg. 19SP: "xewhouse & Sullivan. 1989: Ohlson &
Hogstedt. 1985: Thomas et al. 1982: Liddell et al. 1992 and others detected no signifi cant excess mortality amongst workers exposed to low levels of chrvsotile. Moreover, the low levels of exposure, as defined in some of tnese studies, are still much higher than current occupational exposure limns.
Fibre Dimensions Mediate "RespirahiLitv" and Carcinogenicity
Progress in the stud)' of asbestos and other fibres made during the last 15 years has confirmed tha: fibre length and diameter are important parameters to consider
evaluating carcinogenic potential. Fibre dimensions are important in that the;, determine whether a fibre is "respirabie . Some particles or fibres are too large to infiltrate into the lungs. They are blocked by the body's natural filtration system. .Although some larger fibres are able to find their way into the lungs, many are still too iarge to penetrate deep into tire alveoli and as such are not a carcinogenic risk. Those fibres, which are capable of bypassing these physical barriers, generally fibres of up to 5um in diameter, have been termed "res pirable". Thus in order for fibres to have carcinogenic potential, they must first be of respirable size. Scientists are clear to pointout however that respirability. though nec essary. is not sufficient in explaining car cinogenic potential. Fibres which are res pirable are not necessarily carcinogenic.
A significant body of research has examined why some fibres of respirable size are either less carcinogenic or not carcinogenic at ail. Several factors seem to come into play. Generally speaking, there is ample evidence from experimental studies which demon strates that while long, thin fibres are asso ciated with pathological manifestations in animais. no such association is found with fibres shorter than 5pm long.
In 1989. world-renowned epidemiologist Sir Richard Doll, indicated that "there is increasing evidence that short fibres -- properly described as elongated particles -- are much less carcinogenic, if they are car cinogenic at all. We should base our esti mate of potential risk on both tire chemical constitution of the fibres and their size, counting onlv those fibres that are repirabie ana more than 5um lone1' (1ARC bcientiric Publication No. 90. Lyon).
in attempting to explain this phenomenon. researchers nave discovered that short fibres
can be cleared hv the body's natural defens es without provoking inflammation or mesothelial injury. However, long fibres appear to induce the secretion ot inflamma tory substances bv macrophage cells: A recent report by scientists at the Institute of Occupational Medicine in Edinburgh, has identified such a substance called TNF or Tumor Necrosis Factor, which is released by activated alveolar macrophages.
As scientists have continued to unravel the reasons for the pathogenicity of longer, res pirable fibres, they have discovered that fibre iength alone cannot explain the wide variance in the carcinogenic potential of different substances. Different fibres of sim ilar dimensions mav van' significantly in tneir health effects. With the evolution of new techniques of chemical and mineral analysis, referred to as tissue burden, an additional parameter of fibrous materials is now recognized as of paramount impor tance to our understanding of the patho genic potential of respirable fibres.
Chrvsotile Low on the Continuum of In Vivo Durability
Durability varies widely among different respirable fibres, it appears to be related to a substance's chemical composition and crystalline configuration. In terms of health effects, researchers have focussed on the extent to which the durability of a sub stance determines its "hiopersistence'1. or the length of time which inhaled fibres per sist in the lung betore thev are eventually dissolved and/or cleared. In general, the longer an inhaled particle persists in tire lung, the more likeiy it is to adversely affect surrounding tissues.
Biopersistence studies have been carried out on a number of different respirable fibres.
'see (MiwinsenicitY on pane A
HWBUI0013196
Changes Required to Fibre
A workshop on fibre toxicology conducted by the .National Institute of Environmental Health Sciences (NIEHS) came to a similar conclusion. Its summary indicated that "A major failing of past experimental studies has been the use of mass as the main dose
its. It is only logical that research pro grams devised to better understand the nature of the health effects of fibrous materials provide data in a manner that is meaningful and useful to those concerned with protecting worker safety.
Research
A) THE EXPERIMENTS AS CARRIED OUT
Methodology
The practice of using fibre mass rather than number does not allow for accurate compar isons of the health effects of different fibres
It is widely known that different fibre types have different masses. A similar mass of two different fibrous materials can vary significantly in fibre number (see table).
David L. Coffin, of the U.S. Center for Environmental Medicine and Lung Biology and his former EPA colleagues P.M. Cook and J.P. Creason have warned for many years against inappropriate compar ison of pathological potential of different fibre preparations when only gravimetric (measurements of weight) units were used to report biological effects.
Dosage used
MMVF10* MMVF1V RCP
Mass 30 mg/M3 30 mg/M3 30 mg/M3
Flbra number 232 1lee 240 f/cc
187 f/cc
Observations following 24 months exposure
5 hrs/day: 5 days/week
Wagner PGS+: 25 to 3
Wagner PGS: 2.5 to 3
Wagner PGS: 4 Lung tumours: 16(13.0%) Mesotheiioma: 2(l!6%)
Aramid**
Not stated
100 f/cc
Fibrosis and cystic keratinizing squamous tumours
Chrysotile*
10 mg/M3
10 600 f/cc
Wagner PGS: 4 Lung tumours: 13 (18%) Mesothelioma: 1 (1.4%)
B) THE EXPERIMENT WHICH WAS NEVER CARRIED OUT
Chrysotile
O.IBmg/M3
200 l/ce
?
* Hesterberg, T.W. et at. (1993), Fund. Apot. Toned, (in the press) ' * Lee, K.P. et al. (1988), Fund. Appi. Toxicol. 11:1-20
* PGS: Wagner Pathology Gradng Scale
Cellular ehangea
Fibroale
1. Normal
4. Minimal; MnimaJ fibrosis
2. Minimal; Macrophage response
5. MU: Linking fibrosis
3. Mild; inflammation. bronchiofeation
6. Moderate: Consolidation
7. Seven: Marked fibrosis and consoSdation
8. Severe: Complete obstruction of most airways
Dose-response research using mass rather thanfibre counts has resulted in overestimations ofthe health effects ofchrysotile asbestos.
The need for a meaningful common mea surement unit is underscored by a recent study by Hesterberg et al. (in press) of the health effects of man-made vitreous fibres (MMVF). For the purposes of comparison, the authors included the results of concur rent studies on the effects of refractoryceramic fibres (RCF) and chrysotile asbestos. Close scrutiny of the experimen tal design reveals that the results reportee are from animals exposed 6 hrs/day x ; days/wk for 24 months to -250 f/ml for
MMYFs. -180 f/ml for RCF and 10.000
f/ml ior chrvsotiie asbestos'
parameter. Data are needed on fibre com parisons by fibre number... Most studies using fibres in vitro have in the past expressed dosage on the basis of fibre mass as opposed to number of fibres per cell, which now appears to be a more valid means of comparison of fibre effects in relation to their potential to cause human disease."
In addition, the results of air monitoring are expressed in f/cc. as are exposure iim-
References:
Coffin. D.L.. Cook. P.M. & Creason. J.P. Relative Mesothelioma induction in Rats by Mineral Fibres: Comparison with Residual Pulmonary Mineral Fiber Number and Epidemiology. Inhal Toxicol. 1992:4:2_J-300.
Dement. I.M. Overview: Workshop on Fiber Toxicology-Research Needs. Environ Health Perspect 1990:88:261-268.
Dunnipan. I. Comparing Biological Effects of Mineral Fibres. Brit. I. Ind. Meil.. 1989. 46 : 681-682.
Hesterburg et al. Chronic inhalation toxictty ofsize-separated glassfibers in Fischer s-ta rats. Fund Appl Toxicol, (in press'
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HWBUI0013197