Forms Of Asbestos Research Articles

Human epidemiology: a review of fiber type and characteristics in the development of malignant and nonmalignant disease.

Consideration of the human epidemiology of diseases arising from exposure to naturally occurring and man-made mineral fibers encompasses the several forms of asbestos (chrysotile, crocidolite, amosite, anthophyllite, tremolite-actinolite), other naturally occurring silicates (talc, sepiolite, erionite, attapulgite, vermiculite, and wollastonite), and man-made mineral fibers (glass continuous filament, glass/rock/slag insulation wools, ceramic and other refractory fibers, and glass microfibers). The diseases arising from exposures to some of these fibers include pleural thickening (plaques, diffuse pleural thickening, and calcification), pulmonary fibrosis, lung cancers, mesothelioma of the pleura and peritoneum, and other cancers). Risk factors important in assessing these diseases include assessment of latency, duration of exposure, cumulative exposure, fiber origin and characteristics (length and diameter), other possible confounding occupational or environmental exposures, and smoking. Methodological issues commonly presenting problems in evaluation of these data include assessment of the adequacy of environmental exposures, particularly in regard to fiber identification, distribution, and concentration over the duration of exposure, and the adequacy of study design to detect health effects (disease frequency, latency, and cohort size). Research priorities include further assessment and standardization of pleural thickening relative to fiber exposure, uniform mesothelioma surveillance, further epidemiological assessment of certain silicate and man-made mineral fiber cohorts with emphasis given to assessment of tremolite and small diameter glass and ceramic fibers. Further assessment of possible health risks of the general public should await improved definition of relevant fiber exposure in ambient air.

Human Epidemiology: A Review of Fiber Type and Characteristics in the Development of Malignant and Nonmalignant Disease

Consideration of the human epidemiology of diseases arising from exposure to naturally occurring and man-made mineral fibers encompasses the several forms of asbestos (chrysotile, crocidolite, amosite, anthophyllite, tremolite-actinolite), other naturally occurring silicates (talc, sepiolite, erionite, attapulgite, vermiculite, and wollastonite), and man-made mineral fibers (glass continuous filament, glass/rock/slag insulation wools, ceramic and other refractory fibers, and glass microfibers). The diseases arising from exposures to some of these fibers include pleural thickening (plaques, diffuse pleural thickening, and calcification), pulmonary fibrosis, lung cancers, mesothelioma of the pleura and peritoneum, and other cancers). Risk factors important in assessing these diseases include assessment of latency, duration of exposure, cumulative exposure, fiber origin and characteristics (length and diameter), other possible confounding occupational or environmental exposures, and smoking. Methodological issues commonly presenting problems in evaluation of these data include assessment of the adequacy of environmental exposures, particularly in regard to fiber identification, distribution, and concentration over the duration of exposure, and the adequacy of study design to detect health effects (disease frequency, latency, and cohort size). Research priorities include further assessment and standardization of pleural thickening relative to fiber exposure, uniform mesothelioma surveillance, further epidemiological assessment of certain silicate and man-made mineral fiber cohorts with emphasis given to assessment of tremolite and small diameter glass and ceramic fibers. Further assessment of possible health risks of the general public should await improved definition of relevant fiber exposure in ambient air.

Many Asbestos Removal Projects Cited As Needless, Costly, and Risky

Federal policies that do not distinguish among the different forms of asbestos are needlessly encouraging costly and dangerous asbestos removal projects in schools and other buildings, according to...

Analytical Electron Microscopy of mineral fibers from human lungs

A major application of analytical electron microscopy is in the analysis of mineral fibers recovered from lung tissue and the correlation of these findings with various human diseases. The best studied group of mineral fibers in this regard is asbestos, which is a generic term for fibrous crystalline silicates which possess the properties of high tensile strength, heat resistance, and relative resistance to various chemicals. Chrysotile is the form of asbestos which accounts for the great majority of industrial consumption in this country, with the commercial amphiboles amosite and crocidolite providing the remainder. Non-commercial varieties of amphibole asbestos, including tremolite, anthophyllite, and actinolite, are important primarily as contaminants of other mineral ores. A number of diseases or pathologic abnormalities have been described as resulting from exposure to airborne asbestos fibers, including a form of pulmonary interstitial fibrosis referred to as asbestosis, malignant (diffuse) mesothelioma of the pleura or peritoneum, parietal pleural plaques, and bronchogenic carcinoma, especially among asbestos workers who smoke.

Characterization of cytotoxic effect of asbestos on normal human fibroblasts.

Using viable cell counting and the incorporation of radioactive thymidine in cell TCA precipitate, we have attempted to separate the effects of asbestos on cell growth inhibition (reproductive failure) vs. cell killing. NIEHS crocidolite and NIEHS intermediate-sized chrysotile at a concentration of 10 micrograms/mL were studied. Cytotoxic effects were demonstrated with both types of asbestos. Thymidine incorporation expressed as cpm/viable cell was enhanced in the presence of either form of asbestos. It is concluded that both negatively charged crocidolite and positively charged chrysotile are toxic to human fibroblast cells in culture and exert their cell killing but not growth inhibition effect concurrently with a stimulation of DNA synthesis.

Characterization of Cytotoxic Effect of Asbestos on Normal Human Fibroblasts

Using viable cell counting and the incorporation of radioactive thymidine in cell TCA precipitate, we have attempted to separate the effects of asbestos on cell growth inhibition (reproductive failure) vs. cell killing. NIEHS crocidolite and NIEHS intermediate-sized chrysotile at a concentration of 10 micrograms/mL were studied. Cytotoxic effects were demonstrated with both types of asbestos. Thymidine incorporation expressed as cpm/viable cell was enhanced in the presence of either form of asbestos. It is concluded that both negatively charged crocidolite and positively charged chrysotile are toxic to human fibroblast cells in culture and exert their cell killing but not growth inhibition effect concurrently with a stimulation of DNA synthesis.

Inflammatory particles stimulate thromboplastin production by human monocytes

Several inflammatory particles (zymosan, two forms of asbestos, carrageenan) and the soluble inflammatory agent dextran sulphate induced a dose- and time-dependent increase in thromboplastin activity of cultured human monocytes. Two weakly inflammatory particles (latex and anatase) had little effect. The increase largely depended on protein synthesis; was slow, reaching a peak at about 18 h; and was not due to endotoxin. This procoagulant may contribute to the fibrin deposition frequently seen in inflammatory lesions.

Absence of mutagenic activity of three forms of asbestos in liver epithelial cells

The amosite, crocidolite, and chrysotile forms of UICC asbestos were assayed for their ability to induce gene mutations at the hypoxanthine-guanine phosphoribosyl transferase locus. Using adult rat liver-derived (ARL-6 and ARL-18) cells in culture, no consistent or significant increase occurred in the number of mutants resistant to the purine analog, 6-thioguanine, after exposure to toxic levels of amosite, crocidolite, or chrysotile. These results support the concept that asbestos is an epigenetic carcinogen that does not alter DNA.

Deposition Pattern and Clearance Pathways of Inhaled Chrysotile Asbestos

It has been known for many years that asbestos inhalation leads to a characteristic diffuse interstitial pulmonary fibrosis.1 Chrysotile, the most commonly used form of asbestos, clearly is cytotoxic and has been implicated as an etiologic factor in asbestosis and neoplasia in man and experimental animals.2 Very little is known concerning the early events of particle translocation and cell injury which lead to the characteristic diseases. There seems to be no information available on actual sites of deposition in the most distal anatomic regions of the pulmonary parenchyma.

Asbestos and metals as carcinogens.

Increased incidences of lung carcinoma and pleural mesothelioma in humans exposed to asbestos have been irrefutably established. Different forms of asbestos may have different tumorigenic activities, depending on surface properties, durability, and size of the fibers. A number of metals, such as nickel, chromium, and arsenic, are known to be carcinogenic to humans; for beryllium and cadmium the epidemiologic evidence is less extensive. All these metals also induce genetic toxicity in vitro. For chromium the molecular mechanism of metal tumorigenesis has been extensively investigated; the hexavalent form is generally a much more potent mutagen than is chromium (III). Solubility seems to be necessary for the genotoxicity of nickel. At present it cannot be concluded that all metals act by the same carcinogenic mechanism, even though direct modification of DNA seems to be the common experimental finding.

Comparative toxicities of different forms of asbestos in a cell culture assay

Three forms of Union Internationale Contre le Cancer (UICC) asbestos, amosite, crocidolite, and chrysotile, were assayed for their cytotoxicity (inhibition of colony formation) in cell culture. Using embryonic human intestine-derived (I-407) and adult rat liver-derived (ARL-6) epithelial cells, the order of cytotoxicity was chrysotile > amosite > crocidolite. All three asbestos types were more toxic to I-407 than to ARL-6 cells. Chrysotile, amosite, and crocidolite were also tested for inhibition of colony formation in cultures of mouse colon-derived epithelial-like (MCE-1) cells; these cells were more resistant than the I-407 cells to all three fiber types; although similar to the ARL-6 cells in sensitivity to chrysotile and amosite, the MCE-1 cells were more sensitive to crocidolite then the ARL-6 cells. Leaching of the three asbestos forms for 3 days in sterile deionized water did not appreciably affect the cytotoxicity of I-407 or ARL-6 cells. Leaching in hydrochloric acid, however, greatly decreased the cytotoxicity of chrysotile on these cells and particularly in cultures of ARL-6 cells slightly increased the cytotoxicity of amosite and crocidolite. Leaching in deionized water altered the composition of the asbestos as revealed by release of substantial levels of Mg 2+ and Ca 2+ into the leaching fluid. Greater titers of these ions were released during leaching in hydrochloric acid.

Elemental modifications and polycyclic aromatic hydrocarbon metabolism in human fibroblasts.

Mineral fibers and particulates represent one of the best documented, economically important, and ubiquitously occurring categories of human carcinogens. Yet, while a wealth of information exists concerning the mechanism of action of physical, chemical, and viral carcinogens, virtually nothing is known relative to the mechanism of action of this economically important class of carcinogenic compounds known as mineral fibers and particulates. While the length and diameter of various forms of asbestos have been associated with both cellular toxicity in vitro and tumor occurrence in vivo, nothing is known about whether or not these same physical properties are responsible for the purported synergistic interaction between cigarette smoking and asbestos exposure relative to the induction of bronchogenic carcinoma. Thus, while the risk of bronchogenic carcinoma for nonsmokers exposed to asbestos appears to be only slightly greater than that for unexposed nonsmoking populations, the risk of occurrence of this same tumor in asbestos workers who also smoke is approximately 100-fold greater than in nonsmoking asbestos workers. The risk of bronchogenic carcinoma is increased approximately 8-fold in asbestos workers who smoke over non-exposed smokers. Since it is clear that cigarette smoke contains over 150 polycyclic aromatic hydrocarbons, some of which are known animal carcinogens, and since other laboratories have reported that metals associated with asbestos redirect the metabolism of these agents, it was of interest to us to investigate the effects of mineral fibers on the metabolism and biochemistry of polycyclic aromatic hydrocarbons.

The Effects of Asbestos on Macrophages

The exact role of the alveolar macrophage in the pathogenesis of asbestosis is not known. Most studies of the effect of asbestos on macrophages have been concerned with the in vitro biochemical or cytotoxic properties of the dust and have made use of peritoneal macrophages. In general, chrysotile had a toxic effect on the macrophages, whereas amphibole varieties did not. Most forms of absetos, however, are actively fibrogenic in man and animals, and there is no clear correlation between in vitro cytotoxicity of various forms of asbestos and their fibrogenicity. Recent experiments in which animals are exposed to asbestos in vivo provide evidence of alteration of macrophage activity, as demonstrated by changes in surface morphology and IgG receptor sites, as well as released of various secretory products. Deposition of complement components found on the surface of alveolar marcophages from animals exposed to asbestos could be a manifestation of a humoral immune response directed against an altered cell. The capacity of macrophages to participate in inflammation, tissue repair, and immunity suggests an immunopathogenic concept for the development of asbestosis.

Surface charge and asbestos toxicity.

ASBESTOS is a serious occupational and environmental hazard because of its fibrogenic and carcinogenic actions on the lung. Asbestos fibres exist in various physical forms, all of which are toxic. It is not known, however, which form is the most hazardous or which fibre property is the most important for inducing the toxic effects. It is thus important to examine relationships between the structure of the fibres and their biological activity. We have investigated the relationship between the surface charge and the haemolytic activity (ability to rupture the erythrocyte membrane) of asbestos. We report here that different forms of asbestos can be activated or inactivated by surface charge alterations.

Inorganic particles of agricultural origin.

Substantial quantities of mineral silicates are used as carriers for agricultural pest control agents. Most of this material is applied by air dissemination, either dry or as a droplet spray. Therefore, pulmonary and gastric deposition of the mineral carriers (and active agents) will occur among pesticide application personnel and some proportion of the general population in the vicinity of pest control operations-to the extent that particle size of the disseminated material is below the critical 5mum respirable diameter. Furthermore, ingestion of particulates deposited on food crops may be expected as well as mineral finding its way into drinking water supplies. It has been found that the silicates widely used in America can contain three forms of asbestos, anthophyllite, tremolite, and chrysolite. Of these, anthophyllite and chrysotile have been found associated with a neoplastic outcome after many years of exposure. It is therefore proposed that comprehensive mineralogical investigation of pesticide carriers is warranted, including epidemiological and clinical study of formulation and application personnel as well as exposed nonoccupational populations.

Inorganic Particles of Agricultural Origin

Substantial quantities of mineral silicates are used as carriers for agricultural pest control agents. Most of this material is applied by air dissemination, either dry or as a droplet spray. Therefore, pulmonary and gastric deposition of the mineral carriers (and active agents) will occur among pesticide application personnel and some proportion of the general population in the vicinity of pest control operations—to the extent that particle size of the disseminated material is below the critical 5μm respirable diameter. Furthermore, ingestion of particulates deposited on food crops may be expected as well as mineral finding its way into drinking water supplies. It has been found that the silicates widely used in America can contain three forms of asbestos, anthophyllite, tremolite, and chrysolite. Of these, anthophyllite and chrysotile have been found associated with a neoplastic outcome after many years of exposure. It is therefore proposed that comprehensive mineralogical investigation of pesticide carriers is warranted, including epidemiological and clinical study of formulation and application personnel as well as exposed nonoccupational populations.

Inhalation carcinogenesis from various forms of asbestos

Rats, rabbits, guinea pigs, gerbils, and mice were exposed to the inhalation of chrysotile, crocidolite, or amosite for 2 years. Mean atmospheric concentrations were 47.9–50.2 mg/m 3, but only 0.08–1.82% of the dusts retained fibrous morphology during the dissemination procedure which involved hammer milling. Trace contamination especially by chromium and nickel was also increased. Light microscopic fiber counts per ml chamber air were 54 (chrysotile), 1105 (crocidolite), and 864 (amosite). A fibrogenic response to these dusts was observed in all five animal species, the severity corresponding to the extent of exposure (with reaction to chrysotile frequently very slight). Gerbils developed frequent alveolar proteinosis. Mice developed spontaneous papillary carcinomas in the lungs. Disregarding the latter species, carcinogenic response to asbestos inhalation was restricted to rats and occurred in all three exposure groups. There were 2 lung cancers and 1 pleural mesothelioma after chrysotile inhalation; 4 lung cancers after crocidolite inhalation; and 1 lung cancer and 2 pleural mesotheliomas after amosite inhalation. These cases constituted 7–9% incidence of malignancy among rats with adequate survival record. Hypotheses of asbestos carcinogenesis are reviewed and it is suggested that different etiologic principles may be involved in the causation of lung cancer and of pleural mesothelioma.

Hemolysis by asbestos

Chrysotile asbestos hemolyses erythrocytes within 10 minutes and over a wide range of pH. Other forms of asbestos show varying hemolytic activities which are related to the magnesium:silicon ratio of each form studied. Erythrocytes from different species of animals show different degrees of hemolysis when exposed to chrysotile, amosite, and crocidolite. The length of time during which erythrocytes are exposed to relatively inactive forms of asbestos should also be considered. Amosite and crocidolite show greater hemolytic activities when allowed to react with erythrocytes over 4 hours instead of 1. Ethylenediaminetetraacetic acid (EDTA) effectively prevents hemolysis by chrysotile and other asbestiform materials containing magnesium as a formal part of the lattice. This prevention is pH dependent, however. Sialic acid is even more effective as a preventive agent than EDTA, suggesting that it may contribute the main anionic groups which react with the positively charged magnesiumions on the surface of chrysotile during hemolysis, Poly-2-vinylpyridine-1-oxide, an effective inhibitor of hemolysis by silica powder, has little effect on hemolysis by chrysotile. This again accords with the suggestion that magnesium is the principal agent in hemolysis by asbestos. An association exists between eytotoxicity and hemolytic activity of various forms of asbestos and other minerals although the significance of this is not yet clear.

Crocidolite as a cause of mesothelioma

To the Editor:— Regarding our "Asbestos Bodies and Their Bioeffects" ( 203 :1142, 1968) in which we said that types of asbestos other than crocidolite have been almost com-that crocidolite was almost completely ineffective as a cause of mesothelioma, further information qualifying the relative abilities of crocidolite and other forms of asbestos to produce mesotheliomas has come to hand. According to J. F. Knox (personal communication, March 1968) the Ministry of Labour in Great Britain uses a phrase which is considered preferable to our statement and is offered herewith: [while]... the Advisory Panel considers that the evidence to date on balance indicates a particular significance must be given to crocidolite as a cause of mesotheliomas... it cannot be concluded that only this type of fibre (crocidolite) is concerned with these tumours. In this regard also, Sluis-Cremer reports a high incidence of mesothelioma in one crocidolite mining area of South Africa (Cape

Experimental production of mesothelial tumours of the pleura by implantation of dusts in laboratory animals.

IN view of the possible association between the development of mesotheliomas of the pleura and exposure to asbestos dust in people living in the Cape asbestos fields1,2, a preliminary experiment was undertaken to see if it was possible to produce mesotheliomas, in animals, by injecting various forms of asbestos into the pleural cavities. 110 young rats, mice, and guinea pigs were used. The experiment has not yet been concluded as 45 of the guinea pigs, and four of the rats, are still alive thirty months after the start of the experiment. This is a preliminary report of our positive findings in 106 rats which have either died or have been killed.