E.B. Ilgren

The Biology of Cleavage Fragments: A Brief Synthesis and Analysis of Current Knowledge

Asbestos is a commercial term referring to 6 fibrous minerals from 2 mineralogical classes: serpentine and amphibole. Chrysotile, or white asbestos, is the only serpentine mineral. The asbestiform habit of amphibole asbestos is far more toxic than chrysotile. However, most amphibole minerals are found in the “non-asbestiform” state that pose few, if any, health risks. Comminution, whether deliberate during crushing or grinding, or incidental in usage may produce structures known as “cleavage fragments” from a wide variety of sources. A considerable body of evidence, gathered over the last 30 years, demonstrates that amphibole cleavage fragments do not show the same toxicity as their asbestiform analogues. Since there still continues to be confusion and controversy on this point, this review is aimed at resolving a major portion of this controversy. It has done so by bringing together the supporting mineralogical, animal and human evidence from many sources. These observations demonstrate that cleavage fragments and amphibole asbestos fibres have fundamentally different properties and these differences are biologically relevant. Indeed, the toxicity of respirable cleavage fragments is so much less than that of the fibrous amphiboles that by any reasonable measure they are not biologically harmful.

Coalinga Fibre – A Short, Amphibole-Free Chrysotile

Controversy continues to surround the biological activity of short fibre chrysotile largely due to a lack of ‘pure exposure’ situations available for study: most human exposures are confounded by concomitant long fibre and/or amphibole exposure. This report presents the morphological and morphometric findings of a lifetime inhalation study of F344 rats exposed to three types of chrysotile. Fibres from the first sample, from Coalinga, Calif., are almost all less than 5 µm in length and do not contain amphibole types of asbestos. The other two, from Quebec, Canada, are a sample from the Jeffrey mine and the UICC/B standard. These are both long fibre preparations with a minor degree of amphibole contamination. Animals exposed to these fibres displayed no tumours above control levels following exposure to Coalinga chrysotile but gave significant tumourigenic responses with both types of Canadian fibres.

A Reconnaissance Study of a Potential Emerging Mexican Mesothelioma Epidemic due to Fibrous Zeolite Exposure

A mesothelioma cluster has been found in a remote part of central Mexico. The region is primarily agricultural with no clear source of industrial asbestos exposure. This investigation has revealed that the mesothelioma cluster was situated on an area heavily laden with zeolites. Fibrous erionite was not found. However, the geological conditions and mineralogical characteristics of the affected area very closely resemble those parts of Turkey where mesotheliomas are epidemic and those parts of the western United States where erionite was taken for biological testing. Those biological tests abundantly confirmed the extreme carcinogenicity of erionite for mesothelioma production. This preliminary study should prompt additional investigation to confirm definitively the cause of the elevated mesothelioma risk.

First Confirmed Erionite Related Mesothelioma in North America

Ilgren et al. [1] described in this issue of the Journal a potential emerging Mexican mesothelioma epidemic due to fibrous zeolite exposure. A reconnaissance study was therefore conducted of two mesothelioma cases arising in a father and his son who originally came from a remote part of Mexico in the State of Zacatecas. Further investigation revealed that the small village from whence the father and son came was situated on a zeolite rich geological plain. Additional study of the valley in which the village was situated not only demonstrated geological and mineralogical similarities to the area in Turkey where the first erionite related mesotheliomas were recognized but the appearance of nine other cases ‘‘clustered’’ around the tiny ancestral village where the father and son were born. On the basis of these and other observations described by Ilgren et al. [1], we suggested that erionite, whilst not identified in the area, was almost certainly the causative agent. Over the last 6 months, we recognized two more cases of pleural mesothelioma in a small village in the northern part of the State of Jalisco. This neighbors the southern portion of the State of Zacatecas where the mesothelioma cluster was recognized and is also on the same zeolite rich geological plain. Thus, we once again hypothesized that the two cases found in Jalisco could be due to erionite. Our suspicions have now been confirmed by lung burden analysis of one of the two cases wherein high ‘occupational’ levels (4one million fibers/gram lung dry weight) of fibrous erionite were identified, initially by EDAX and later confirmed by SAED, by Prof. Fred Pooley. This case represents the first erionite related mesothelioma seen in North America unrelated to Turkish erionite exposures. Its discovery further suggests, as Ilgren et al [1] proposed, that detailed follow up investigations are warranted to identify the source of and subsequently prevent further potential toxic fiber exposures. To facilitate such investigations, a brief description is given of the two Jalisco cases and the potential sources of toxic dust exposure that may have caused their mesotheliomas. Thus, the two cases were both men, 50 and 60 years old at the time of diagnosis, and each having pleural mesothelioma. They each spent approximately the first 20 years of their lives in the village and their homes were built for the most part of local earth. Similarly, both were involved in agricultural tilling and storage of various vegetables such as corn and beans whilst they also raised a small amount of livestock including cattle,

Coalinga Fibre: A Short, Amphibole-Free Chrysotile Part 3: Lack of Biopersistence

We previously demonstrated, on the basis of detailed morphological and mor phometric investigations of a lifetime inhalation study of F344 rats exposed to three sizes of chrysotile fibre, that a short, amphibole-free chrysotile from Coalinga, California failed to induce pathological effects whilst the other two, both long fibres from Canada, were both fibrogenic and tumourigenic. Here, we demonstrate that, as one would predict from their size differences, the Coalinga fibre was almost totally cleared whilst the Canadian fibres were largely retained 1 year post exposure. We therefore propose on the basis of these observations that the observed absence of biological effects noted with Coalinga is potentially attributable to its lack of biopersistence.

Coalinga Fibre: A Short-Fibre, Amphibole-Free Chrysotile

Coalinga chrysotile is a short-fibre, amphibole-free asbestos from California. It is prototypic of many other short-fibre chrysotiles found elsewhere in the world. Since short-fibre chrysotile is the most common form of asbestos, a deeper understanding of the biological effects of Coalinga chrysotile should provide important insights into what many regulatory agencies are now calling a major health hazard, the reasoning behind this being that these agencies consider all fibre types to be biologically equivalent. Previously the potential fibrogenicity of Coalinga chrysotile had been assessed in two inhalation bioassays. The first was conducted in 1978 at the National Institutes of Environmental Health and Sciences (NIEHS) in the United States. Our earlier analysis of this investigation demonstrated that Coalinga chrysotile was not fibrogenic. The second inhalation bioassay was conducted in 1983 at the Fraunhofer Institute in Germany by Muhle et al. Unfortunately, in their final analysis, data were presented in a way that did not allow one to determine whether Coalinga chrysotile was fibrogenic or not. Because of this, the slides have been re-examined using the Wagner scoring system, which is designed specifically to assess fibrosis. The findings of this re-evaluation clearly demonstrate, yet again, that Coalinga chrysotile is not fibrogenic in these assays.

Coalinga Chrysotile: A Short Fibre, Amphibole Free, Chrysotile: Part V - Lack of Amphibole Asbestos Contamination

Exposure to asbestos in the indoor built environment has been a concern for many years. The most common exposures in that setting are to short ultra-thin, naturally defibrillated form of fibrous asbestiform chrysotile and possibly trace amounts of short, non-asbestiform amphibole. Coalinga chrysotile is a short fibre mineral that was mined from a large ore body in California. It has been investigated in considerable detail since, although it is widely believed to be amphibole free, evidence for this has not hitherto been summarised. Analytical results from investigations that directly searched for amphiboles and geological studies from which the presence or absence of amphibole can be inferred, have indicated that Coalinga chrysotile is free of amphibole asbestos. Indeed, numerous investigations, performed over almost half a century, using a variety of techniques including the most sensitive methods, and studying many thousands of samples have failed to find any amphibole asbestos in Coalinga chrysotile. Only very rarely have non-asbestiform, “non-friable” amphibole (so-called cleavage fragment) minerals been found in the New Idria serpentine body but away from the ore zone. A large body of animal and human evidence indicates such cleavage fragments lack biological potential.

Health Risks from Exposures to Asbestos, Metals, and Various Chemicals due to Collapse of the World Trade Center: An Environmental Residential Survey with a Commentary Related to Ground Zero Workers1

Environmental monitoring was immediately instituted at Ground Zero (GZ) after the collapse of the World Trade Center (WTC). However, nearby residences were not assessed. To address this, a GZ elected official task force requested an independent residential survey to be done. Its findings, whilst based upon relatively few samples, are still probably the first and most detailed produced to date. Overall, residents do not appear to be at risk of long-term, asbestos – or metal – related disease but their homes must still be cleaned professionally to eliminate highly irritating, aerosolized dusts. Respiratory protection would eliminate the small chance of long-term disease in unprotected cleaners. The risks to GZ workers represent a special case and are discussed in detail.

Coalinga Chrysotile: A Short-Fibre, Amphibole-Free, Chrysotile: Part VI - Additional Evidence for Lack of Fibrogenicity

This report describes additional unpublished data that support the notion that Coalinga chrysotile is not fibrogenic. These data are from the same long-term, NTP-NIEHS, chronic chrysotile inhalation study that served as the basis for our earlier publications which concluded that Coalinga chrysotile was not fibrogenic due to its lack of biopersistence. Wagner-scored 12 and 24 month interim sacrifice data from the NTP-NIEHS investigation and an unpublished data set from the comparison MRC study both previously unreported, were recently found in the author’s files. The histology slides and attendant data should have been amongst the materials archived at the NTP but were not present at the time the author reviewed those files in 1995 and 1996. Review of these new materials showed that Coalinga chrysotile did not produce fibrosis either at 12 or 24 months in contrast to the two Canadian preparations which were both fibrogenic even at this early stage of the study. These new data and related testimony greatly strengthen our earlier conclusions and serve to refute earlier apparently contradictory reports. International and Governmental Reports support the conclusion reached in our papers that Coalinga chrysotile is not pathogenic. In fact, the only scientists to criticise our conclusions have been in litigation against Union Carbide.

Response to the California EPA’s Office of Environmental Health Hazard Assessment Critical Assessment of Ilgren and Chatfield’s Studies of Coalinga Chrysotile’s Fibrogenicity, Tumorigenicity, and Biopersistence

ment (OEHHA), headed by Dr. Melany Marty, Chief of the Air Toxicology and Epidemiology Section, evaluated the findings of the Coalinga chrysotile inhalation bioassays [1] reported in this journal by Ilgren and Chatfield [2-4], together with a paper by Muhle et al. [5] and other related papers. In that evaluation, Marty levelled nine different criticisms against these studies which I should like to detail here together with specific points to refute each of them. Thus: