(1/70) A risk assessment for exposure to grunerite asbestos (amosite) in an iron ore mine.
The potential for health risks to humans exposed to the asbestos minerals continues to be a public health concern. Although the production and use of the commercial amphibole asbestos minerals-grunerite (amosite) and riebeckite (crocidolite)-have been almost completely eliminated from world commerce, special opportunities for potentially significant exposures remain. Commercially viable deposits of grunerite asbestos are very rare, but it can occur as a gangue mineral in a limited part of a mine otherwise thought asbestos-free. This report describes such a situation, in which a very localized seam of grunerite asbestos was identified in an iron ore mine. The geological occurrence of the seam in the ore body is described, as well as the mineralogical character of the grunerite asbestos. The most relevant epidemiological studies of workers exposed to grunerite asbestos are used to gauge the hazards associated with the inhalation of this fibrous mineral. Both analytical transmission electron microscopy and phase-contrast optical microscopy were used to quantify the fibers present in the air during mining in the area with outcroppings of grunerite asbestos. Analytical transmission electron microscopy and continuous-scan x-ray diffraction were used to determine the type of asbestos fiber present. Knowing the level of the miner's exposures, we carried out a risk assessment by using a model developed for the Environmental Protection Agency. (+info)
(2/70) In situ microscopic analysis of asbestos and synthetic vitreous fibers retained in hamster lungs following inhalation.
Hamsters breathed, nose-only, for 13 weeks, 5 days/week, 6 hr/day, either man-made vitreous fiber (MMVF)10a, MMVF33, or long amosite asbestos at approximately 300 World Health Organization (WHO) fibers/cc or long amosite at 25 WHO fibers/cc. [World Health Organization fibers are longer than 5 microm and thicker than 3 microm, with aspect ratio >3.] After sacrifice, fiber burden was estimated (left lungs) by ashing and scanning electron microscopy (ashing/SEM) or (right middle lobes) by confocal laser scanning microscopy (CLSM) in situ. In situ CLSM also provided three-dimensional views of fibers retained, undisturbed, in lung tissue. Fibers of each type were lodged in alveoli and small airways, especially at airway bifurcations, and were seen fully or partly engulfed by alveolar macrophages. Amosite fibers penetrated into and through alveolar septa. Length densities of fibers in parenchyma (total length of fiber per unit volume of lung) were estimated stereologically from fiber transsections counted on two-dimensional optical sections and were 30.5, 25.3, 20.0, and 81.6 mm/mm3 for MMVF10a, MMVF33, and low- and high-dose amosite, respectively. Lengths of individual fibers were measured in three dimensions by tracking individual fibers through series of optical sections. Length distributions of amosite fibers aerosolized, but before inhalation versus after retention in the lung were similar, whether determined by ashing/SEM or in situ CLSM. In contrast, the fraction of short MMVF10a and MMVF33 fibers increased and the geometric mean fiber lengths of both MMVFs decreased by approximately 60% during retention. Most likely due to fiber deposition pattern and differences in sampling, fiber burdens [MMVF10a, MMVF33, and amosite (high dose; 269 WHO fibers/cc)] determined by ashing/SEM were 1.4, 1. 5, and 3.5 times greater, respectively, than those calculated from in situ CLSM data. In situ CLSM is able to provide detailed information about the anatomic sites of fiber retention and also fiber lengths and burdens in good agreement with ashing/SEM results. (+info)
(3/70) Asbestos induction of extended lifespan in normal human mesothelial cells: interindividual susceptibility and SV40 T antigen.
Normal human mesothelial cells from individual donors were studied for susceptibility to asbestos-induction of apoptosis and generation of an extended lifespan population. Such populations were generated after death of the majority of cells and arose from a subset of mesothelial cultures (4/16) whereas fibroblastic cells (5/5) did not develop extended lifespan populations after asbestos exposure. All mesothelial cultures were examined for the presence of SV40 T antigen to obtain information on (i) the presence of SV40 T antigen expression in normal human mesothelial cells and (ii) the relationship between generation of an extended lifespan population and expression of SV40 T antigen. Immunostaining for SV40 T antigen was positive in 2/38 normal human mesothelial cultures. These cultures also had elevated p53 expression. However, the two isolates expressing SV40 T antigen did not exhibit enhanced proliferative potential or develop an extended lifespan population. Asbestos-generated extended lifespan populations were specifically resistant to asbestos-mediated but not to alpha-Fas-induced apoptosis. Deletion of p16Ink4a was shown in 70% of tumor samples. All mesothelioma cell lines examined showed homozygous deletion of this locus which extended to exon 1beta. Extended lifespan cultures were examined for expression of p16Ink4a to establish whether deletion was an early response to asbestos exposure. During their rapid growth phase, extended lifespan cultures showed decreased expression of p16Ink4a relative to untreated cultures, but methylation was not observed, and p16Ink4a expression became elevated when cells entered culture crisis. These data extend the earlier observation that asbestos can generate extended lifespan populations, providing data on frequency and cell type specificity. In addition, this report shows that generation of such populations does not require expression of SV40 T antigen. Extended lifespan cells could represent a population expressing early changes critical for mesothelioma development. Further study of these populations could identify such changes. (+info)
(4/70) Biopersistence and durability of nine mineral fibre types in rat lungs over 12 months.
The study objectives were to assess the ability of intratracheal injection methods to discriminate between nine fibre types in respect of pulmonary biopersistence, and to provide approximate estimates of relative biopersistence and durability for a study of general relationships with biological and toxicological responses. The test fibres included six samples of size-selected fibre types specially prepared for research purposes, two commercially available fibres, and amosite. A 1 mg dose of each fibre type was administered to rats by intratracheal injection. The relative biopersistence of fibres in different size categories was assessed from the changes in mean lung burden, as determined by electron microscopy, at 3 days and 1, 6 and 12 months after injection. The ability of the test materials to resist dissolution was measured in a parallel series of simple in vitro acellular experiments at two pHs and in a continuous flow dissolution test. The observed differences in the persistence of fibres of differing length recovered from rat lungs were consistent with the current hypothesis that short fibres are cleared by cellular processes and long fibres by dissolution and disintegration. Differences in persistence of long (> 20 microns) fibres were correlated with measured rates of dissolution in vitro. Differences in persistence among those fibre types also studied by others workers were consistent with their findings after inhalation and intratracheal injection. Overall, the differences in the biopersistences of the test fibres following intratracheal injection were sufficient to enable an examination of the relationship of biopersistence with other biological and toxicological responses. Biopersistence was influenced by both fibre dimensions and solubility. (+info)
(5/70) Influence of fibre length, dissolution and biopersistence on the production of mesothelioma in the rat peritoneal cavity.
A range of respirable man-made mineral fibres were tested for evidence of carcinogenicity by injection into the peritoneal cavity of male SPF Wistar rats; and differences in carcinogenicity were related to the dimensions and biopersistence of the injected fibres. The fibres tested included an amosite asbestos, a silicon carbide whisker, a special purpose glass microfibre, and a range of other man-made vitreous fibres (MMVFs) and refractory ceramic fibres (RCFs) from the TIMA fibre repository. The injected dose of each was designed as the estimated mass required to contain 10(9) fibres > 5 microns in length, as determined by optical microscopy. The numbers of long fibres (> 15 microns) contained in these doses ranged across fibres from 0.1 x 10(9) to 0.8 x 10(9) fibres; the number of long fibres thinner than 0.95 micron ranged from 0.015 x 10(9) to 0.4 x 10(9). The treatment groups contained between 18 and 24 animals. Animals were killed when they showed signs of debilitation. At autopsy, the diagnosis of mesothelioma was usually obvious macroscopically. Otherwise, histological examination of peritoneal organs was used to search for early tumour development. Judged by median survival time, four of the fibre types, in the doses administered, presented higher mesothelioma activity than amosite asbestos. The other fibres tested were less carcinogenic than the amosite. Only a ceramic material derived by extreme heating to simulate the effect of furnace or oven conditions, produced no mesotheliomas. Attempts were made, using regression models, to relate these differences to fibre dimensions and to measures of durability from separate experiments. The results pointed principally to a link with the injected numbers of fibres > 20 microns in length and with biopersistence in the rat lung of fibres longer than 5 microns. Improved quantification of the relative importance of fibre dimensions and biopersistence indices requires experimentation with a range of doses. (+info)
(6/70) Impact of acute and subchronic asbestos exposure on some parameters of antioxidant defense system and lung tissue injury.
Asbestos fibers have been used in industry for decades. Deleterious effect of asbestos on the lungs has been documented. However, the mechanism of asbestos related diseases has not been fully explained yet. Numerous papers suggest there is a role of reactive oxygen intermediates (ROI) in asbestos-induced lung disease development. The excess ROI produced can be removed from the lungs by enzymatic and nonenzymatic antioxidants. The aim of our study was to compare the levels of antioxidants (ascorbic acid, retinol, alpha-tocopherol, glutathionperoxidase) as well as some markers of lung injury (lipid peroxides, total amount of protein, alkaline phosphatase) in asbestos treated Wistar-rats both 24 hr and 3 months after exposure to those in the controls, and to find out if the changes in antioxidant levels could affect impairment of the lungs. Decreased levels of antioxidants and increased values of lung tissue injury parameters in exposed groups suggest involvement of ROI in the mechanism of asbestos lung disease development, resulting in lung tissue injury, both 24 hr and 3 months after exposure. (+info)
(7/70) Chemical differences between long and short amosite asbestos: differences in oxidation state and coordination sites of iron, detected by infrared spectroscopy.
OBJECTIVES: Short fibres of amosite asbestos (SFA), obtained by ball milling of long fibres (LFA), have been shown to be less pathogenic than long fibres. Accumulating evidence suggests an important role for differences in surface chemistry between fibres. Iron has been implicated in the pathogenesis of asbestos fibres. In this study infrared (IR) spectroscopy was used to compare LFA and SFA in terms of the coordination and oxidation state of iron at the three cation sites (M1, M3, M1). METHODS: Infrared was used to examine LFA ad SFA, when dry and when hydrated in the presence and absence of the chelators desferroxamine and ferrozine. With appropriate software the proportions of iron and its oxidation states in the overlapping peaks were resolved and assigned, and the three coordination sites were identified. Data were obtained from 10 samples of both lengths of fibre for each of the four treatments. Iron release was also monitored. RESULTS: Iron was significantly more oxidised in LFA than SFA. Further oxidation of the dry fibres with water, ferrozine, or desferroxamine tended to abolish these differences. There were also significant differences between the proportions of iron held in the different coordination sites of the fibres. For LFA, a higher proportion of its iron was held in the cation sites coordinating less with iron and more with Mg. Interestingly, the sites coordinating single irons were significantly more oxidised than multiple sites. The single iron sites were more oxidised in LFA than SFA and were more readily oxidised by the treatments. CONCLUSIONS: Important chemical differences between LFA and SFA were found. There seemed to be some mobility of iron near the surface. Based on these data it is speculated that the 1 iron surface site may be important in pathogenesis. (+info)
(8/70) TNF-alpha increases tracheal epithelial asbestos and fiberglass binding via a NF-kappaB-dependent mechanism.
Tumor necrosis factor (TNF)-alpha is released from alveolar macrophages after phagocytosis of mineral fibers. To determine whether TNF-alpha affects the binding of fibers to epithelial cells, we exposed rat tracheal explants to TNF-alpha or to culture medium alone, followed by a suspension of amosite asbestos or fiberglass (MMVF10). Loosely adherent fibers were removed from the surface with a standardized washing technique, and the number of bound fibers was determined by scanning electron microscopy. Increasing doses of TNF-alpha produced increases in fiber binding. This effect was abolished by an anti-TNF-alpha antibody, the proteasome inhibitor MG-132, and the nuclear factor (NF)-kappaB inhibitor pyrrolidine dithiocarbamate. Gel shift and Western blot analyses confirmed that TNF-alpha activated NF-kappaB and depleted IkappaB in this system and that these effects were prevented by MG-132 and pyrrolidine dithiocarbamate. These observations indicate that TNF-alpha increases epithelial fiber binding by a NF-kappaB-dependent mechanism. They also suggest that mineral particles may cause pathological lesions via an autocrine-like process in which the response evoked by particles, for example, macrophage TNF-alpha production, acts to enhance subsequent interactions of particles with tissue. (+info)