The advantages and limitations of an in vivo test system for investigating the cytotoxicity and fibrogenicity of fibrous dusts.
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The acute response of the rat lung to a range of fibrous materials has been investigated by bronchopulmonary lavage, at dose levels of 0.5 and 1.0 mg, 1 and 7 days after their administration by intratracheal instillation. The materials chosen for study included UICC chrysotile A, amosite, crocidolite and anthophyllite, and samples of S. African "long" amosite and glass fiber. In addition, the subacute response to 1, 2 and 3 mg of chrysotile and amosite has been studied at 50 and 100 days after instillation. In the acute phase at 1 day after instillation, the response to chrysotile was greater than that to any of the other materials, but by 7 days there was no gradation in the response to different dusts. In the subacute phase, cell recoveries were low, and it was not possible to assess the long-term cytotoxic or fibrogenic effects of amosite and chrysotile by analyses of lung washes, even though biochemical and histological methods indicated gross changes in lung pathology. (+info)
Study of the cell-transforming ability of amosite and crocidolite asbestos and the ability to induce changes in the metabolism and macromolecular binding of benzo(a)pyrene in C3H10T1/2 cells.
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The cell transforming ability of asbestos dusts was investigated using C3H10T1/2 murine fibroblasts. In a series of experiments, crocidolite and amosite caused no increase in the number of transformed colonies over that seen in cultures from untreated cells. The dusts were, however, capable of augmenting the oncogenic effect of benzo(a)pyrene. This synergistic effect was evident when fibers and chemicals were added to cultures as simple mixtures and when benzo(a)pyrene was adsorbed to the surface of fibers. Asbestos dust did not, however, appear to exert its oncogenic enhancing effect by modifying the metabolism of benzo(a)pyrene in C3H10T1/2 cells. (+info)
Measurement and analysis of chemically changed mineral fibers after experiments in vitro and in vivo.
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Asbestos, as well as other natural and man-made mineral fibers used for in vitro and in vivo experiments, must be described and defined physically and chemically as exactly as possible before any application. The interactions of fibers with the physical, chemical (air, water, etc.) and biological (cells, tissues, etc.) environments cause important changes in fiber chemistry and crystalline structure. Also, these should be detected as precisely as possible after each experiment. Our recent investigations dealt with the development of a complex analytical system for such measurements and with some applications of these analytical procedures for fibrous material sampled in the environment and from biological materials. Chemical and physical microanalyses of asbestos and glass fibers obtained by environmental sampling (air, water) and from human and animal tissue have shown chemical and crystalline changes in these particles. Scanning electron microscopy, electron microprobe analysis and mass spectrometry analysis were used in these investigations. A partial or total leakage of elements could be observed. The leakage of elements in fibers is of a statistical nature. Some fibers remained chemically unchanged; in some fibers some elements were partially leached; and in some fibers the majority of metallic elements were leached. The potential meaning of this effect is also discussed. (+info)
Effect of intrabronchially instilled amosite on lavagable lung and pleural cells.
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Rats were instilled intrabronchially with 1 mg UICC amosite suspended in 0.2 mL of filtered saline; control animals received the saline instillation only. Five animals from each group were killed on various days after instillation, up to day 128/129. Total retrieved cell counts and differential cell analysis were performed from lung and pleural lavages. In particular, the appearance of peroxidase-positive macrophages (PPM) as indicators of newly arrived macrophages was investigated. Polymorphonuclear cells (PMN) and PPMs in lung lavages increased in number 24 hr after amosite instillation and remained at increased levels until day 62. Alveolar macrophage numbers were significantly decreased after amosite instillation. There was only a very transient increase of PPMs and PMNs in the saline group. The number of PPMs in pleural lavage fluid was already increased 24 hr after amosite instillation. The pleural PPM increase was sustained throughout the study. No pleural reaction was seen in the saline instilled group. The inflammatory reactions indicated by the composition of the lavaged cells of the lung represent the in vivo toxicity of intrabronchially instilled amosite. The stimulus for recruitment of PMNs and PPMs is different, since no PMN response was detected in the pleural space. It is suggested that the response of the pleural PPMs is caused by the early arrival of fibers at the pleural sites, which results in the recruitment of PPMs to this space by an unknown mechanism. (+info)
Correlation of in vitro and in vivo methods by means of mass dose and fiber distribution for amosite and fibrous ferroactinolite.
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Oncogenesis and in vitro data (reported elsewhere in detail) are compared on the basis of relative activity by mass and by dimensional fiber parameters. When tumor induction is compared to the number of fibers of various lengths and aspect ratios in the dose in rats to the degree of tumor induction, a degree of difference with the long thin fiber concept of tumorigenesis by mineral fibers is noted. Consistency is re-established, however, when cognizance is taken of the change in the length and aspect ratio that took place during residence in the lung. This change resulted in a severalfold excess for ferroactinolite of all fiber lengths with high aspect ratios, produced as a result of longitudinal splitting of the introduced fibers. The response by mass in the in vitro procedures did not mimic oncogenesis. When mass was so adjusted that there were an equal number of mineral fibers, aspect ratio greater than 3, for dose for the two minerals, agreement was closer in both the rabbit alveolar macrophage toxicity test and the clonal cytotoxicity assay in Chinese hamster ovary cells. When activity was related to the number of mineral fibers, the same aspect ratio computed to have been contained in the mass dose, agreement with the relative induction of lung tumors was closer. In all cases, erythrocyte lysis was more active in reflecting the number of mineral fibers. (+info)
Chronic effects of dietary exposure to amosite and chrysotile asbestos in Syrian golden hamsters.
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Bioassays of amosite, short-range (SR), intermediate-range (IR) or intermediate-range chrysotile asbestos in combination with the intestinal carcinogen 1,2-dimethylhydrazine dihydrochloride (DMH) were conducted with male and female Syrian golden hamsters. Amosite and both forms of chrysotile asbestos were administered at a concentration of 1% in pelleted diet for the entire lifetime of the hamsters starting with mothers of the test animals. Group sizes varied from 125-254. There was no adverse effect on body weight gain or survival by either type of asbestos or by IR chrysotile asbestos in combination with DMH. A significant increase (p less than 0.05) in adrenal cortical tumors was observed in male hamsters exposed to SR and IR chrysotile asbestos and in females treated with IR chrysotile asbestos when compared to the pooled control groups. However, statistical significance (p less than 0.05) was lost when these dosed groups were compared with temporal control groups. Neither of the male or female amosite asbestos groups showed increased neoplasia in any tissue or organ compared to the control groups. The cocarcinogen studies using IR chrysotile asbestos and 1,2-dimethylhydrazine dihydrochloride were considered inadequate because there was no increase in intestinal neoplasia in the DMH group. (+info)
Chronic effects of dietary exposure to amosite asbestos and tremolite in F344 rats.
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Carcinogenesis bioassays of blocky (nonfibrous) tremolite and amosite asbestos alone or in combination with the intestinal carcinogen 1,2-dimethylhydrazine dihydrochloride (DMH) were conducted with male and female Fischer 344 rats. The minerals were administered at a concentration of 1% in pelleted diet for the entire lifetime of the rats starting with the dams of the test animals. One group of amosite rats also received chrysotile asbestos via gavage during lactation. Group sizes varied from 100 to 250 animals. The offspring from mothers exposed to tremolite or amosite asbestos were smaller at weaning than those from untreated mothers and remained smaller throughout their life. The administration of dimethylhydrazine (DMH) did not affect body weight gain, either in amosite-exposed or nonexposed animals. Survival was comparable in the tremolite and control groups. The amosite-exposed rats showed enhanced survival compared to the untreated controls. DMH exposure reduced survival by approximately one year, although the amosite plus DMH groups survived slightly better than the DMH alone groups. No toxicity or increase in neoplasia was observed in the tremolite-exposed rats compared to the controls. Significant increases (p less than 0.05) in the rates of C-cell carcinomas of the thyroid and monocytic (mononuclear cell) leukemia in male rats were observed in amosite-exposed groups. However, the biological significance of the C-cell carcinomas in relation to amosite asbestos exposure is discounted because of a lack of significance when C-cell adenomas and carcinomas were combined and the positive effect was not observed in the amosite plus preweaning gavage group. The biological significance of an increased incidence of mononuclear cell leukemia is questionable, because of a lack of statistical significance in the amosite group when evaluated using life table analysis, lack of significance when compared to the tremolite control group, and the fact that no toxic or neoplastic lesions were observed in the target organs, i.e., gastrointestinal tract and mesothelium. DMH caused a high rate of (62-74%) of intestinal neoplasia in amosite and nonamosite-exposed groups. Neither an enhanced carcinogenic nor protective effect was demonstrated by exposure to amosite asbestos. (+info)
Fiber size and number in amphibole asbestos-induced mesothelioma.
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Numbers and sizes of fibers from the lungs of 10 patients who had an amphibole asbestos-induced malignant pleural mesothelioma were analyzed. Amosite was found in 10 lungs and crocidolite in 9; the average ratio of amosite to crocidolite was approximately 14:1. In the 8 patients who were not long-time asbestos insulators , the mean number of amosite fibers was 2.3 X 10(6) fibers/g dry lung, and of crocidolite fibers, 0.2 X 10(6)/g; these values represent an approximately 250-fold increase over those found in the general population. Crocidolite fibers were significantly narrower than amosite fibers (mean width, 0.13 versus 0.23 mu), were significantly shorter (mean length, 4.0 versus 5.8 mu), and had a significantly higher mean aspect (length to width) ratio (48 versus 34). Aspect ratios in general increased with increasing fiber length and decreasing fiber width, but the highest values were found for thin amosite fibers at about 13 mu in length, and thin crocidolite fibers at 8 or 15-17 mu in length. Comparison with data from other asbestos-exposed populations indicates that mesothelioma can be induced by relatively small numbers of amphibole fibers and also indicates that amosite is an effective mesothelial carcinogen in humans. Comparison of these data with epidemiologic and experimental predictions of carcinogenic size ranges for mesothelioma induction implies that either the carcinogenic size range is much broader than has been claimed (in particular, fibers considerably shorter than 8 mu and broader than 0.05 mu can produce mesothelioma), or, alternately, that extraordinarily small absolute numbers of fibers in certain size ranges can induce tumors in humans. (+info)