1. Background

Of the options proposed by Directorate General III of the European Commission, the CSTEE chose, in the first instance, the following as the simplest for consideration:

"On the basis of the available data, do any of the following substitute fibres pose an equal or greater risk to human health than chrysotile asbestos?

- Cellulose fibres

- PVA fibres

- P-aramid fibres

Particular consideration should be given to the relative risk to para-occupational workers and other users of the asbestos-containing products in comparison to non-asbestos products"

The CSTEE acknowledged the existence of risks for fibre-exposed workers in occupations (e.g. building maintenance, construction workers) other than mining, processing and using asbestos materials. It was also aware that in some circumstances asbestos fibres in the atmosphere in the general (non-occupational) environment have reached concentrations producing damage or creating concern. Nevertheless, the CSTEE felt that its terms of reference allude, on a qualitative basis, to the inherent hazardous properties of the materials to be compared. It is obvious that for chrysotile, for its candidate substitutes, as well as for any environmental hazard, quantitative risk assessment is also determined by dose and therefore by environmental concentrations.

The CSTEE terms of reference did not include potential hazards and risks for the environment of any of the materials taken into consideration. The CSTEE understands that Chrysotile asbestos may be replaced, in some of its uses, by non-fibrous materials, including polyvinylchloride (PVC), whose potential hazards are out of the scope of the present opinion.

All documents that were submitted to the CSTEE were examined in detail. The documents have been listed by the CSTEE Secretariat as CSTEE/97/2 Adds 1-42 and where appropriate have been quoted in the text. A recent report dealing directly to the question posed to the CSTEE was issued by the University of Leicester Institute for Environment and Health "Chrysotile and its substitutes: a critical evaluation" on 6 April 1998 (CSTEE 97/2 Add. 18). Thus, particular attention was given to other documents commenting, or criticising it.

The problem of whether or not there is a safe level of chrysotile exposure, raised by some documents (CSTEE 97/2 Adds. 20, 21, 22, 34, 35) submitted by the European Advisory Council of the Asbestos International Association and by Spanish scientists was considered outside the terms of reference of the Committee. Chrysotile is a proven carcinogen and there is not sufficient evidence that it acts through a non-genotoxic mechanism. Thus a cautionary approach is that there is no threshold for the carcinogenic effect of this agent. Regarding the candidate substitutes, there is neither evidence of carcinogenicity nor reliable toxicological information for identifying no effect levels, if any. Thus, a consideration of the issue of thresholds, at this point in time, would be non-productive.

References to published papers are numbered throughout the text and quoted in section 8 of the present document. Only a small number of the reviewed studies were addressed to direct comparisons between the effects of the different types of fibres to be considered by the CSTEE. No attempt has been made to verify that studies relevant to the question posed to the CSTEE have been exhaustively identified. Nevertheless, the CSTEE believes that no study that may change its conclusions (see paragraph 7) has been omitted from consideration.

2. Long-term carcinogenic effects in exposed humans

Epidemiological studies on workers exposed to chrysotile have been reviewed on several occasions. The International Agency for Research on Cancer (1) has recognised that there is sufficient evidence of carcinogenicity for all forms of asbestos (including chrysotile). A similar evaluation has been expressed in a review on chrysotile prepared by the International Programme on Chemical Safety - IPCS (2), which summarises the present knowledge in the following terms:

"The overall relative risks for lung cancer are generally not elevated in the studies of workers in asbestos, cement production and in some of the cohorts of asbestos-cement production workers. The exposure-response relationship between chrysotile and lung cancer risk appears to be 10-30 times higher in studies of textile workers than in studies of workers in mining and milling industries... The reasons for this variation in risk are not clear...

Estimation of the risk of mesothelioma is complicated ... by factors such as the rarity of the disease, the lack of mortality rates in the populations used as reference, and problems in diagnosis and reporting. In many cases ..., crude indicators have been used, such as absolute numbers of cases and deaths ...

... the largest number of mesotheliomas has occurred in the chrysotile mining and milling sector. All the observed 38 cases (in Quebec) were pleural with the exception of one ... None occurred in workers exposed for less than 2 years. There was a clear dose-response relationship, with crude rates of mesotheliomas (cases/1000 person-years) ranging from 0.15 for those with cumulative exposure of less than 3530 million particles per cubic meter-years .. to 0.97 for those with exposures of more of more than 10590 mpcm-years ...

There is evidence that fibrous tremolite causes mesothelioma in humans. Since commercial chrysotile may contain fibrous tremolite, it has been hypothesised that the latter may contribute to the induction of mesotheliomas in some populations exposed primarily to chrysotile. The extent to which the observed excess of mesothelioma might be attributed to the fibrous tremolite content has not been resolved".

The CSTEE endorses these conclusions. Notice was taken of recent updates of the prospective mortality studies among miners in Quebec (3, 4, 5, 6) which lead the authors to stress further the "tremolite hypothesis" on the basis that: a) in miners and millers in Quebec virtually all of the risks for both mesothelioma and lung cancer have been conferred by exposure to chrysotile in the areas known to be the most heavily contaminated with tremolite and b) even at the most hazardous mines and mills only workers with long and heavy exposure seem to be at any increased risk of either lung cancer or mesothelioma.

The CSTEE does not believe that these new estimates detract from the evaluation that chrysotile is a human carcinogen. Mesotheliomas have been recently described in women living in the mining area of Quebec (7). This type of tumour has also been reported in workers extracting chrysotile in Italy (see 8 for most recent update), and China (9), as well as in studies in the asbestos-cement production, textile and friction material manufacture where commercial chrysotile but no amphiboles were used (2). It must be recognised that in practice it is not possible to know the precise composition (and extent of contamination by amphiboles, if any) of commercial chrysotile used in different settings, including those which have been investigated in epidemiological studies. Lung cancer risk estimates vary up to a factor of 1:50 between chrysotile miners and textile workers exposed to commercial chrysotile and this may well be due to different levels of exposure and/or to changes brought about by processing in the morphology of the fibres (10).

No epidemiological studies or observations in humans of long term effects of p-aramid or PVA have been reported in the scientific literature, probably because of the limited number of person-year-observation corresponding to the likely latent period of human cancer. In fact, p-aramid has been sold commercially since 1972 but the production in fibrous form started more recently (11). PVA has been produced commercially since 1936 (12).

A recent review (13) summarises published studies on 4 cohorts of workers exposed to cellulose fibres. The underlying activities were paperwood, pulp and paper, soft paper mill and cellulose production. Excesses of cancer deaths were reported in some of the studies but no consistent target site emerges from these studies. An excess of lung cancer deaths in the study addressed to the pulp and paper industry was not standardised for smoking habits.

3. Effects other than cancer in exposed humans

The potential of chrysotile to induce non-neoplastic lung damage has been known for a long time. As summarised by the IPCS (2):

"The non-malignant diseases associated with exposure to chrysotile comprise a somewhat complex mixture of clinical and pathological syndromes not readily definable for epidemiological study. The prime concern has been asbestosis, generally implying a disease associated with diffuse interstitial pulmonary fibrosis accompanied by varying degrees of pleural involvement.

Studies of workers exposed to chrysotile in different sectors have broadly demonstrated exposure-response or exposure-effect relationships for chrysotile-induced asbestosis, in so far as increasing levels of exposure have produced increases in the incidence and severity of disease. However, there are difficulties in defining this relationship, due to factors such as uncertainties in diagnosis and the possibility of disease progression on cessation of exposure.... Asbestotic changes are common following prolonged exposure of 5 to 20 f/ml".

There is uncertainty and debate regarding whether the two pathological end-points of asbestosis and lung cancer are independent or whether fibrosis is a necessary pre-requisite for cancer (14). For all forms of asbestos, the associations with both end points have broadly similar dose-response relationships, similar latent periods and depend in the same way on fibre length (15).

To the knowledge of the CSTEE, no cases of lung fibrosis have been reported among workers exposed to either p-aramid, cellulose or PVA fibres. In fact, the medium and long-term effects of each of these three agents on the lung function and morphology have been investigated to a limited extent.

One study failed to demonstrate any short-term (up to one year) effect on respiratory function of exposure to p-aramid fibres and SO2 compared to a control group that may have been inadequate (16). Dermatoses may occur in workers exposed to p-aramid, at an unknown frequency (17).

As for cellulose fibres, the above mentioned study on workers in the soft paper mill production unit (13) exhibited excess mortality from chronic obstructive pulmonary disease and asthma, with no excess of cancer deaths (which renders unlikely confounding by tobacco). Workers in this unit also exhibited a decrease in lung vital capacity and residual pulmonary volume, a finding considered by the authors to represent non specific reactions to the heavy exposure to paper dust in the mill.

4. Long-term effects in laboratory animals

In rats, chrysotile has produced mesotheliomas and lung carcinomas after inhalation and mesotheliomas after intrapleural administration. It induced mesotheliomas in hamsters following intrapleural administration and peritoneal mesotheliomas in mice following intraperitoneal injection. Results of experiments in which chrysotile was given orally to rats or hamsters have been equivocal (1). For most of these experiments, it is not known whether and to which extent the chrysotile, which was administered to animals, was contaminated with amphiboles.

The carcinogenicity of para-aramid fibrils has been tested in one adequately conducted inhalation study in rats (18). The pathology (and thus the underlying biological significance) of keratinising lung lesions found in ten rats (of an original number of 229) has been the object of a series of revisions (see review in 12) by international panels of animal pathologists. It has been concluded that these lesions are non-neoplastic and irrelevant to evaluation of cancer risks for humans. Limited data from experiments by intraperitoneal injection of p-aramid to rats did not suggest carcinogenic effects (11).

No adequate long-term carcinogenicity experiment with either cellulose fibres of PVA has been reported in the published literature (19).

5. Toxicity

Recent studies have compared the clearance of p-aramid and chrysotile fibres from rat and hamster lung after inhalation at equal target concentrations (20-22). P-aramid fibrils were clearly less biopersistent overall than chrysotile. The changes over time in the numbers of fibres remaining in the lung, and in their size distribution, suggested that in the case of p-aramid the number of shorter fibrils was increased initially by fragmentation of longer ones, and then decreased. This was confirmed in a more recent sub-chronic inhalation study with p-aramid in rats (23). The longer chrysotile fibres, on the other hand, did not fragment and were preferentially retained, presumably because they were too long to be cleared by alveolar macrophages. It is accepted that in general only longer fibres can be carcinogenic (see section 6).

In another study, high doses of p-aramid caused an increase in lung-cell proliferation, though the effect was small and had disappeared in the rat by 5 days after the end of the 2-week exposure period, and by 1 month in the hamster. At the same level of exposure, chrysotile markedly increased cell proliferation in airway, alveolar and sub-pleural tissue during 0-3 months post-exposure (24).

Available data regarding the toxicity of cellulose fibres have recently been reviewed (13). These fibres were found to be toxic to mouse macrophages in vitro, as shown by the release of lactic dehydrogenase. This was not confirmed subsequently with rat macrophages, although a high dose of cellulose did cause a transient inflammatory response in vivo (25). Cellulose fibres have been shown to be as effective as chrysotile in stimulating macrophages to release inflammogenic substances such as interleukin-1, and were more effective than asbestos in stimulating the release of prostaglandins. The interpretation of this finding is difficult. In another recent study, cellulose powder instilled into rat lung produced a persistent granulomatous response (26), but the high dose used would certainly have caused "overload" and thus inhibited normal clearance by macrophages.

Very little information is available on the pulmonary toxicity of PVA fibres in laboratory animals.

As for genotoxicity, a search of the relevant experiments in the databank of the Istituto Superiore di Sanità, Rome (whose exhaustivity was confirmed through a parallel search at the International Agency for Research on Cancer) produced the following summary evaluations:

Chrysotile (CAS 12001-29-5) is clastogenic and aneugenic in mammalian cells in vitro. Tests for SCE and gene mutation induction in mammalian cells are contradictory. Negative results are reported in bacterial systems and in an UDS assay. In vivo, no clastogenic effect is observed in bone marrow after ip or oral administration. The latter results should be evaluated with caution due to the lack of information on the availability of chrysotile to the target tissue.

P-aramid (CAS 24938-64-5) was inactive in gene mutation tests in bacteria in mammalian cells. No adequate evaluation of genotoxicity can be done.

No data have been found for polyvinyl alcohol (CAS 9002-89-5) and for cellulose fibres (CAS 9004-34-6).

6. Characteristics of the fibres being compared

According to the standard definition, a fibre has a length/diameter ratio of at least 3:1. Falling speed in air is proportional to the square of the diameter and directly proportional to bulk density, whereas fibre length is less significant in this context. Thus, diameter determines the length of time a fibre will remain suspended in air and air concentration. Further, the "respirable fraction" excludes almost completely mineral fibres whose diameter exceeds 3 microns and organic fibres whose diameter exceeds 7 microns. It is commonly believed that a potential carcinogenic hazard may exist with fibres longer than 8-10 micra, diameter smaller than 3 micra and a length/diameter ration greater than 3:1 (16).

After inhalation, durability of fibres is a major determinant of integrated dose. Long fibres deposited in the alveoli are cleared slowly by macrophages. Residence time (i.e. biopersistence) is determined by the dissolving rate, which depends on the fibre chemical composition and on their ability to undergo fragmentation (a transverse break of the filament into shorter pieces which may not meet the 3:1 ratio), either by mechanical flexure within the lung tissue or by partial dissolution in the acidic environment within the macrophage. Fibrillation, instead, is the process through which respirable smaller fibres are produced and is thus an indicator of carcinogenic risk.

The following are the characteristics of the fibres considered in the present report (27):

Length Diameter Fibrillation

Micra micra

Chrysotile > 5 < 1 +++

PVA > 5 10-16 +/-

P-aramid > 5 10-12 + (need much abrasion to produce many fibrils)

Cellulose > 5 12-40 exposure data suggest very limited fibril production

7. Conclusion

A major concern with fibres is their carcinogenic potential. There is sufficient evidence that all forms of asbestos, including chrysotile, are carcinogenic to man. No evidence of fibre-caused cancer occurrence in man is available for any of the three candidate substitutes. Admittedly, for cellulose fibres, this may reflect limitations in the design of the underlying studies, whereas the lack of epidemiological studies on PVA and p-aramid may be due to the relatively short time elapsed since the onset of industrial uses of these materials.

Lung fibrosis is a well-known consequence of chrysotile exposure, but to-date no case has been reported in workers exposed to any of the three candidate substitute fibres.

Chrysotile is an established experimental carcinogen in laboratory animals. Of the candidate substitutes, only p-aramid has been tested in adequately designed long-term inhalation experimental studies, which did not provide evidence of carcinogenicity.

Overall, acute and subacute toxicity data on the three substitute fibres are very meagre and do not allow for a proper comparison with chrysotile, with the possible exception of p-aramid, which in a series of experiments in rats was shown to cause less inflammation and cellular proliferation than chrysotile given at similar doses. In vitro, the ability of cellulose to induce certain inflammation-related changes seems greater than that of chrysotile.

Fibre characteristics, such as size, respirability, biopersistence and fragmentability, indirectly provide elements for an overall comparison of potential effects between different types of fibres. Current knowledge on the mechanisms of long-term toxicity of fibrous materials in humans based on such characteristics is consistent with the inference that substitutes are less harmful than commercial chrysotile.

On the basis of the above, in the opinion of the CSTEE the ability of cellulose, PVA or p-aramid fibres to induce cancer or fibrosis of the lung in man is likely to be lower than that of chrysotile.

The limited amount of toxicological studies on the three candidate substitutes leaves wider margins of uncertainty in order to predict their ability to produce effects other than cancer and lung fibrosis. Nevertheless, the available data on current levels of exposure and fibre characteristics suggest that the amount of fibres of critical size and shape reaching the human pulmonary alveoli is very limited.

Thus, both for the induction of lung and pleural cancer and lung fibrosis - i.e. the end point conditions investigated to a greater extent - and for other effects, it is unlikely that either cellulose, PVA or p-aramid fibres pose an equal or greater risk than chrysotile asbestos. With regard to carcinogenesis and induction of lung fibrosis, the CSTEE has reached a consensus that the risk is likely to be lower.

The CSTEE recommends these conclusions not to be interpreted in the sense that environmental control of the workplaces where the substitute fibres are produced or used can be relaxed. Finally the CSTEE strongly recommends expansion of research in the areas of toxicology and epidemiology of the substitute fibres as well as in the technology of development of new, thicker (less respirable) fibres.

8. References

1. IARC Monographs on the Evaluation of Carcinogenic Risk to humans. Supplement 7, International Agency for Research on Cancer, Lyon 1987.

2. IPCS Environmental Health Criteria on Chrysotile (in press 1998).

3. McDonald JC, McDonald AD Chrysotile, tremolite and carcinogenicity Ann Occup Hyg 1997; 41:699-705.

4. Liddell FDK, McDonald AD, McDonald JC: The 1891-1920 birth cohort of Quebec chrysotile miners and millers: development from 1904 and mortality to 1992 Ann Occup Hyg 1997; 41:13-36.

5. McDonald AD, Case BW, Churg A. et al. Mesothelioma in Quebec chrysotile miners and millers: epidemiology and aetiology Ann Occup Hyg 1997; 41:707-719

6. Liddell FDK, McDonald AD, McDonald JC Dust exposure and lung cancer in Quebec chrysotile miners and millers Ann Occup Hyg 1998; 42:7-20

7. Camus M, Siemiatycki J., New Engl J Med 1998; 338

8. Silvestri S, Magnani C, Calisti R, Bruno C The health effects of mining and milling chrysotile asbestos and the health experience of the community living close to the mine: the experience of the Balangero asbestos mine in Italy, Proceedings of the International Workshop on the Health Effects of Chrysotile Asbestos: Contribution of Science to Risk Management Decisions, Montreal 1997.

9. Zou SQ, Wu YX, Ma FS, Ma HS, Sueng WZ, Jjiang ZH Retrospective mortality study of asbestos workers in Laiyuan. Proc Int Pneumocon Conf - Part II, Aug 23-26 1988. NIOSH-DHHS Publ No 90-108, NIOSH, Pittsburgh PA 1990, pp 1242-44.

10. Landrigan P. Asbestos - still a carcinogen New Engl J Med.

1998; 338:1618-1619.

11. International Agency for Research on Cancer IARC Monographs on the Evaluation of Carcinogenic Risk to humans. Vol. 68, International Agency for Research on Cancer, Lyon 1997.

12. International Agency for Research on Cancer IARC Monographs on the Evaluation of Carcinogenic Risk to humans. Vol. 19, International Agency for Research on Cancer, Lyon.

13. Davies JMG: The toxicity of wool and cellulose fibres J Occup Health Safety Australia New Zealand 1996; 12:341-344.

14. Egilman D, Reinert A. Lung cancer and asbestos exposure: asbestosis is not necessary. Am J Ind Med 1996; 30:398-406.

15. Meldrum M. Review of fibre toxicology. Health and Safety Executive, London 1996.

16. Pal TM, Schaaphok J, Coenraads J Lung function of workers occupied in drawing and treatment of aramid fibres (in French) Cah Notes Doc 1990; 138:254-257.

17. Reinhardt CF: Toxicology of Aramid Fibres. In Proceedings of the National Workshop on Substitutes for Asbestos. USEPA, July 14-16, 1980, pp. 443-444.

18. Lee KP, Kelly DP, O'Neal FO, Stadler JC, Kennedy GL. Lung response to ultrafine Kevlar aramid synthetic fibrils following 2-year inhalation exposure in rats. Fundam Appl Toxicol 1988; 11:1-20.

19. PHS 149: Survey of compounds which have been tested for carcinogenicity

20. Searl A. A comparative study of the clearance of respirable para-aramid, chrysotile and glass fibres from the rat lungs. Ann Occup Hyg 1997; 41:217-233.

21. Warheit DB, Hartsky MA, Butterick CJ, Frame SR. Pulmonary toxicity studies with man-made organic fibres: preparation and comparisons of size-separated p-aramid with chrysotile asbestos fibres. In Toxicology of Industrial compounds Thomas H, Hess R, Waechter F eds. pp 119-130, Taylor and Francis, London 1995).

22. Warheit DB, Snajdr SI, Hartsky MA, Frame SR. Pulmonary responses to inhaled para-aramid fibrils in hamsters: evidence of biodegradability in the lungs of a second rodent species. Inhal Toxicol 1996; 110:1-6).

23. Fraunhoffer Institut Toxicologie und Aerosolforschung: Final report on an inhalation tolerance study for p-aramid respirable fibre-shaped particulates (RFP) in rats. Fraunhoffer Institute, Hanover, 1998.

24. Warheit DB, Snajdr SI, Hartsky MA, Frame SR Lung proliferative and clearance responses to inhaled p-aramid RFP in exposed hamsters and rats: comparisons with chrysotile asbestos fibres. Environ Health Persp 1997; 105 (suppl 5):1219-1222.

25. Adamis Z, Tatrai E, HonnaK, Ungvary G In vitro and in vivo assessment of the pulmonary toxicity of cellulose J Appl Toxicol 1997; 17:137-141.

26. Tatrai E, Brozik M, Adamis Z, Meretey K, Ungvary G In vivo pulmonary toxicity of cellulose in rats. J Appl Toxicol 1996; 16:129-135.

27. UK Committee on the Carcinogenicity of Chemicals in Food, Consumer Products and the Environment (COC): Statement for Health and Safety Executive (HSE) on carcinogenic risk of three chrysotile substitutes, London July 1998.

List of documents made available to the Scientific Committee on Toxicity, Ecotoxicity and the Environment via its Secretariat to help it reach the opinion requested by the services of the Commission on the subject of "Chrysotile asbestos and candidate substitutes"

CSTEE/97/2

Recent assessments of the hazards and risks posed by asbestos and substitute fibres, and recent regulation of fibres world-wide - Final report - November 1997 - DG III.

CSTEE/97/2 - Add. 1

A constructive commentary on :

The June 1997 draft final report prepared for the European Commission DGIII by environmental resources management, Oxford, entitled "recent assessments of the hazards and risks posed by asbestos and substitute fibres, and recent regulation of fibres world-wide" - GW Gibbs, JMG Davis, J. Dunnigan and RP Nolan - 6/9/1997.

CSTEE/97/2 - Add. 2

Answers and comments to the terms of reference regarding the document prepared by ERM for the DGIII. - Fax from Dr. Lambré (INERIS) - 5/1/1998.

CSTEE/97/2 - Add. 3

CSTEE - Chrysotile asbestos - Fax from Dr. Dybing (Folkehelsa) - 9/1/1998.

CSTEE/97/2 - Add. 4

A note on the document - dated November 1997 - "Recent assessments of the hazards and risks posed by asbestos and substitute fibres, and recent regulation of fibres world-wide", commissioned by DGIII prepared to Environmental Resources Management, Oxford (ERM)

Made by Dr. B. Terracini - 30/1/1998.

CSTEE/97/2 - Add. 5

Rapport ERM à la DG III, Référence 4259 Novembre 1997. - Fax envoyé par Prof. Dr. R. Wennig - Luxembourg, 4/2/1998.

CSTEE/97/2 - Add. 6

Observations of the EAC (European Advisory Committee of the A.I.A.) with regard to the report of 9th February 1998 of the Scientific Committee on Toxicity, Eco-toxicity and the Environment of the DG XXIV (Chrysotile).

From A.I.A. (Asbestos International Association).

CSTEE/97/2 - Add. 7

The Health Risks from Chrysotile - Discussion between British and Canadian experts, Rose Court, 30 September 1997.

Draft report from Health and Safety Executive - 12/12/1997.

CSTEE/97/2 - Add. 8

Estimation of the continuous Emission of Asbestos in the Atmosphere.

By Dr.-Ing. J. Michatz (German Association of Fibre-Cement Industries).

CSTEE/97/2 - Add. 9

Cellulosefasern zur Herstellung von Faserzement.

By K. Uebersax-Ingold, U.F. Gruber - Universität Basel, Toxikologie (1992).

CSTEE/97/2 - Add. 10

Zur Charakterisierung einiger Ersatzfaserstoffe und deren Wirkung im Tierversuch.

By K.H. Friedrichs, M. Rosenbruch, H.W. Schlipköter - Heinrich-Heine-Universität, Düsseldorf (1990).

CSTEE/97/2 - Add. 11

Working group "limitations on marketing use of dangerous substances and preparations (asbestos).

By Dr. Rolf Packroff - Federal Institute for Occupational Safety & Health - Dortmund - 10/3/1998.

CSTEE/97/2 - Add. 12

Selected synthetic organic fibres - Environmental Health Criteria 151 - First draft prepared by Dr. M.E. Meek (Ottawa).

World Health Organisation, Geneva, 1993.

CSTEE/97/2 - Add. 13

In Vivo Pulmonary Toxicity of Cellulose in Rats (1995).

Article in Journal of Applied Toxicology, Vol. 16(2), 129-135 (1996).

CSTEE/97/2 - Add. 14

Chrysotile asbestos and candidate substitutes: proposed terms of reference.

DG III/C/4 - April 1998.

CSTEE/97/2 - Add. 15

Cancer Mortality among Man-Made Vitreous Fibre Production Workers

Keywords : man-made vitreous fibres, lung cancer, occupational diseases, mesothelioma, man-made mineral fibres, cohort study.

P. Boffetta, ...Epidemiology - May 1997, Volume 8 Number 3.

CSTEE/97/2 - Add. 16

IEH report on Natural and man-made mineral fibres : UK research priorities - Report R3 from Medical Research Council - Institute for Environment and Health (1995).

CSTEE/97/2 - Add. 17

BK-Report 1/94

FASER JAHRE - Berufsgenossenschaftliche Hinweise zur Ermittlung der kumulativen Asbestfaserstaub-Dosis am Arbeitsplatz - (Faserjahre) und Bearbeitungshinweise zur Berufskrankheit Nr. 4104 (Lungenkrebs)

From HVBG (Sankt-Augustin) - 1994.

CSTEE/97/2 - Add. 18

Chrysotile and its substitutes : a critical evaluation.

An IEH unpublished report for the Health and Safety Executive - 6 April 1998 - From the Institute for Environment and Health (Leicester University).

CSTEE/97/2 - Add. 19

Executive Summary.

Made by a Group for the Study of Risks of the Asbestos and Alternative Materials (MM. Costas, Goyanes & Garrido-Pertierra) - Department of Biochemistry and Molecular Biology IV - Universidad Complutense de Madrid.

CSTEE/97/2 - Add. 20

Report on Chrysotile (according to the Commission Directive 93/67/EEC on Risk Assessment for new notified Substances and the Commission Regulation EC/1488/94 on Risk Assessment for existing Substances).

Made by a Group for the Study of Risks of the Asbestos and Alternative Materials (MM. Costas, Goyanes & Garrido-Pertierra) - Department of Biochemistry and Molecular Biology IV - Universidad Complutense de Madrid.

CSTEE/97/2 - Add. 21

Five evidences of a safe level of chrysotile exposure.

Made by a Group for the Study of Risks of the Asbestos and Alternative Materials (MM. Costas, Goyanes & Garrido-Pertierra) - Department of Biochemistry and Molecular Biology IV - Universidad Complutense de Madrid.

CSTEE/97/2 - Add. 22

Report on alternative Materials for Chrysotile : substitute fibres and polyvinyl chloride (PVC). Health, Environmental and Energetical Risks.

Made by a Group for the Study of Risks of the Asbestos and Alternative Materials (MM. Costas, Goyanes & Garrido-Pertierra) - Department of Biochemistry and Molecular Biology IV - Universidad Complutense de Madrid.

CSTEE/97/2 - Add. 23

Presentation at the "Chrysotile asbestos" working group meeting of 9/6/98 in Paris.

CSTEE/97/2 - Add. 24

Presentation by industries representatives on the purported risks of Chrysotile asbestos and substitutes - Prof. A. Garrido Pertierra - "Chrysotile asbestos" working group meeting of 9/6/98 in Paris.

CSTEE/97/2 - Add. 25

List of legislation and exceptions in Member States which have introduced restrictions (revised) - DG III - February 1998.

CSTEE/97/2 - Add. 26

Zur gesundheitlichen Bedeutung der zur Herstellung von Faserzement verwendeten Asbestersatzfasern - Medizinisches Institut für Umwelthygiene an der Heinrich-Heine-Universität Düsseldorf.

CSTEE/97/2 - Add. 27

Short account of the exchange of information which took place during the Working Group meeting on Chrysotile Asbestos in Paris (9/6/1998).

CSTEE/97/2 - Add. 28

IPCS Environmental Health Criteria on Chrysotile - Chapter 1 "Summary".

CSTEE/97/2 - Add. 29

Opinion on a study commissioned by Directorate General III (Industry) of the European Commission on Recent Assessments of the Hazards and Risks Posed by Asbestos and Substitute Fibres, and Recent Regulation of Fibres World-Wide (Environmental Resources Management, Oxford).

Opinion expressed at the 2nd CSTEE plenary meeting - Brussels, 9th February 1998.

CSTEE/97/2 - Add. 30

Effets sur la santé des fibres de substitution à l'amiante.

Rapport établi par "Expertise Collective" de l'INSERM à la demande de la Direction Générale de la Santé et de la Direction des Relations du Travail (Ministère de l'Emploi et de la Solidarité) - Paris, juin 1998.

CSTEE/97/2 - Add. 31

Research on Asbestos Health Problems in the U.S.S.R. (Ref. 16).

Report sent to EU from Russia for consideration by the Scientific Committee.

CSTEE/97/2 - Add. 32

Possibility of inducing glandular stomach cancer in rats exposed to asbestos.

Report sent to EU from Russia for consideration by the Scientific Committee.

CSTEE/97/2 - Add. 33

Eighth Finnish-Soviet Symposium on Occupational Health - 26-29 August 1991 - Nauvo, Finland - Extended Abstracts (Institute of Occupational Health - Helsinki, Finland).

Report sent to EU from Russia for consideration by the Scientific Committee.

CSTEE/97/2 - Add. 34

Low dose chrysotile asbestos exposure increase health risk ? : an undecidable dilemma.

Report from E. Costas & A. Garrido (Univ. Complutense de Madrid) and V. Goyanes (Hospital Teresa Herrera - La Coruña, Spain).

CSTEE/97/2 - Add. 35

The asbestos question : a comparative bibliometric analysis of pros and cons papers.

Report from E. Costas & A. Garrido (Univ. Complutense de Madrid) and V. Goyanes (Hospital Teresa Herrera - La Coruña, Spain).

CSTEE/97/2 - Add. 36

Asbestos alternatives : will that be to go from bad to worse ?.

Report from E. Costas & A. Garrido (Univ. Complutense de Madrid) and V. Goyanes (Hospital Teresa Herrera - La Coruña, Spain).

CSTEE/97/2 - Add. 37

Informe final del contrato de investigacion n° 5280589 entre Uralita sa y la Universidad Complutense de Madrid.

CSTEE/97/2 - Add. 38

Further restrictions on asbestos : scientific opinion.

Letter from Dr. Jeanie Cruickshank, Head Chemical Policy Division - HSE (UK) - 16/7/1998.

CSTEE/97/2 - Add. 39

Commentaires sur le rapport Costas, Goyanes et Garrido-Pertierra.

Lettre du Prof. Wennig au Prof. Terracini - 16/7/1998.

CSTEE/97/2 - Add. 40

Final report on an "Inhalation Tolerance Study for p-Aramid Respirable Fibre-Shaped Particulates (RFP) in Rats" produced by the Fraunhofer Institute (August 1998).
This document was sent to the CSTEE by the firm Dupont, Engineering fibres.

CSTEE/97/2 - Add. 41

"Toxicological Assessment of Respirable Fibre-shaped Particulates (RPF) derived from p-Aramid" (authors: V. Foà and S. Basilico) (September 1997).
This document was sent to the CSTEE by the firm Dupont, Engineering fibres.

CSTEE/97/2 - Add. 42

TUTB text on Asbestos.

Letter from Marc Sapir, Director BTS.TUTB.TGB (B) dated 3/9/1998 + 3 enclosures.

CSTEE/97/2 - Add. 42/A

Report from Andrea Tozzi on Asbestos "Time to come clean" - August 1998.

CSTEE/97/2 - Add. 42/B

TUTB Newsletter Nr 7 - December 1997.

CSTEE/97/2 - Add. 42/C

TUTB Newsletter Nr 9 - June 1998.