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Biomedical subjects

P Sébastien

Publications and source records attributed to P Sébastien.

At least 19 recordsLinked to original sources
PubMed2001

Effects of nonfibrous particles on ceramic fiber (RCF1) toxicity in rats.

In previous investigations a reference test sample of prepared ceramic fibers called RCF1 induced lung tumors in a 2-yr inhalation study in rats. It was hypothesized that nonfibrous particles in RCF1 may have played a significant role. The objective of the present study was to compare lung retention and biological effects of another sample of ceramic fibers, called RCF1a, to the original RCF1. The main difference between these 2 samples was the content of nonfibrous particles: 25% of the mass of RCF1 versus 2% for RCF1a. These nonfibrous particles were chemically identical to the fibers. Female Wistar rats were exposed 6 h/day, 5 days/wk for 3 wk to either RCF1a or RCF1 fiber aerosol at a concentration of about 125 fibers (>20 microm long)/ml. Because of differences in the nonfibrous particle contents, the average gravimetric aerosol concentration differed between the two samples (RCF1, 51.2 mg/m(3); RCF1a, 25.8 mg/m(3)). The posttreatment observation period was 12 mo. Biological effects measured include the clearance function of alveolar macrophages (clearance of fibers and tracer particles), and inflammation and its persistence during the recovery period. Alveolar clearance of tracer particles ((46)Sc(2)O(3)) was barely retarded after RCF1a exposure (80 days clearance half-time compared to 60 days in controls). After RCF1 exposure, however, a severe retardation of clearance was observed (1200 vs. 66 days). In both groups, differential cell counts on pulmonary lavage showed a significant increase of polymorphonuclear leukocytes (PMNs) (about 15%) and lymphocytes 3 days after the end of exposure. The PMN influx persisted longer after exposure to RCF1 than RCF1a. The conclusion of the study is that the particle fraction of RCF1 significantly enhanced any adverse effects. This clearly demonstrates the importance of the physical characteristics of the test material for the degree of toxic effects to be expected. The presence of nonfibrous particulates can enhance the effects on the lung of a mixture of fibrous and nonfibrous particulates following exposure.

Administration, Inhalation↗
PubMed1997

Mesothelioma in Quebec chrysotile miners and millers: epidemiology and aetiology.

In a cohort of some 11,000 men born 1891-1920 and employed in the Quebec chrysotile production industry, including a small asbestos products factory, of 9780 men who survived into 1936, 8009 are known to have died before 1993, 38 probably from mesothelioma--33 in miners and millers and five in factory workers. Among the 5041 miners and millers at Thetford Mines, there had been 4125 deaths from all causes, including 25 (0.61%) from mesothelioma, a rate of 33.7 per 100,000 subject-years; the corresponding figures for the 4031 men at Asbestos were eight out of 3331 (0.24%, or 13.2 per 100,000 subject-years). At the factory in Asbestos, where all 708 employees were potentially exposed to crocidolite and/or amosite, there were 553 deaths, of which five (0.90%) were due to mesothelioma; the rate of 46.2 per 100,000 subject-years was 3.5 times higher than among the local miners and millers. Six of the 33 cases in miners and millers were in men employed from 2 to 5 years and who might have been exposed to asbestos elsewhere; otherwise, the 22 cases at Thetford were in men employed 20 years or more and the five at Asbestos for at least 30 years. The cases at Thetford were more common in miners than in millers, whereas those at. Asbestos were all in millers. Within Thetford Mines, case-referent analyses showed a substantially increased risk associated with years of employment in a circumscribed group of five mines (Area A), but not in a peripherally distributed group of ten mines (Area B); nor was the risk related to years employed at Asbestos, either at the mine and mill or at the factory. There was no indication that risks were affected by the level of dust exposure. A similar pattern in the prevalence of pleural calcification had been observed at Thetford Mines in the 1970s. These geographical differences, both within the Thetford region and between it and Asbestos, suggest that the explanation is mineralogical. Lung tissue analyses showed that the concentration of tremolite fibres was much higher in Area A than in Area B, a finding compatible with geological knowledge of the region. These findings, probably related to the far greater biopersistence of amphibole fibres than chrysotile, have important implications in the control of asbestos related disease and for wider aspects of fibre toxicology.

Aged↗
PubMed1995

Biopersistence of cerium in the human respiratory tract and ultrastructural findings.

For diagnostic purposes, mineralogical analysis was performed in bronchoalveolar lavage fluid and lung tissue from a 58-year-old patient previously exposed to asbestos and rare earth dusts. No significant retention of asbestos was demonstrated in lung tissue by light microscopy (asbestos bodies) or transmission electron microscopy analysis (uncoated fibers). Particles containing rare earth (cerium, lanthanum) and phosphorus were identified in alveolar macrophages in bronchoalveolar lavage fluid, and cerium-containing particles accounted for 70% of particles observed in the lung tissue. Ultrastructural analysis of lung tissue revealed the presence of particles containing cerium and phosphorus in interstitial macrophages and elastic fibers. These results suggest that rare earth is metabolized and should be considered as biopersistent in the human respiratory tract, since occupational inquiries revealed that exposure to cerium oxide abrasive powder had ceased at least 15 years earlier.

Asbestos↗
PubMed1994

Biopersistence of man-made vitreous silicate fibers in the human lung.

There is now a substantial body of experimental data on the pulmonary biopersistence of man-made vitreous silicate fibers (MMVSF), but human data are seriously lacking. Our knowledge in this field is essentially limited to a few reports of measurements of fibers retained in lung tissue samples taken at autopsy from workers manufacturing these products. Three types of exposure were studied: fibrous glass, mineral wool, and refractory ceramic fibers. Overall, the available data do not provide evidence for substantial long-term retention of fibers in the human lung after occupational exposure to MMVSF dusts. A word of caution, however; the amount of data supporting the previous statement is much greater for fibrous glass than for either mineral wool or refractory ceramic fibers. There is no human data on the key question of the kinetics of pulmonary clearance of inhaled MMVSF.

Calcium Compounds↗
PubMed1993

Biological markers as indicators of exposure and pneumoconiotic risk: prospective study.

This research is designed to evaluate a number of biological markers to estimate harmful exposure on coal miners from different mining regions in France and to relate the outcome to differences in prevalence of coal worker pneumoconiosis (CWP) between these regions. Eight epidemiological groups of active and ex-miners (smokers and non-smokers) have been selected in the French collieries (North, Lorraine and Provence) according to their occupational and pneumoconiotic status. The following biomarkers have been evaluated: cellularity of sputum, elementary analysis of particles in TEM/EDAX, plasma neutral metalloendo-peptidase elastase type (NMEP), leucocyte elastase (HLE), fibronectin (FN) and elastin peptides. Pulmonary alveolitis, expressed by sputum cellularity, is different between active workers groups but not related to the general background of pneumoconiosis prevalence in the French collieries. In the plasma parameters, fibronectin, HLE and NMEP significantly increased in all groups of coal mine workers as compared to the control group, except for fibronectin parameter in Lorraine collierie. The degree of increase of these parameters allow us to discriminate the different groups and suggest that plasma FN, HLE and NMEP may be considered as biological markers of chronic inhalation of coal mine dust particles. The decrease of elastin peptides level in the Lorraine group alone suggests a specific alteration of elastin metabolism. These parameters were not related to the development of pneumoconiosis and its degree of severity.

Biomarkers↗
PubMed1993

Pulmonary dust retention in a silicon carbide worker.

This paper reports on pulmonary dust retention in a man who worked 42 years in the vicinity of an Acheson furnace of a silicon carbide plant and had a carborundum pneumoconiosis. Special attention is paid to the retained silicon carbide fibers in the lung parenchyma. The concentration of silicon carbide fibers longer than 5 microns is 39,300 fibers/mg dry lung. These fibers have a similar morphology to fibers observed in the working environment. The result is compared to pulmonary retention of workers exposed to asbestos.

Carbon↗
PubMed1993

Effects of phosphorylation of chrysotile on pleuropulmonary fibrogenicity and carcinogenicity.

As well as fibre size, fibre chemistry is a determinant of toxicity of mineral fibres. On these grounds, a few years ago, the asbestos industry in Québec developed a process to modify the surface chemistry of chrysotile asbestos by fixing phosphorous atoms. The pleuropulmonary fibrogenicity and carcinogenicity of the native and surface treated chrysotile, called chrysophosphate, were tested. Both products initiated similar pulmonary fibrogenicity in rats exposed by inhalation and sheep exposed by injection in the tracheal lobe. Tumour production in rats after long term inhalation or intrapleural injection was not different between chrysotile and chrysophosphate. These findings clearly show that modification of the phosphate surface of chrysotile fibres does not appear to alter the pleuropulmonary activities of the mineral, thus arguing against the earlier contention of less biological activity for chrysophosphate, a contention essentially based upon results of in vitro tests. This study strongly argues for in vivo testing of new fibrous materials before making definite conclusions about their biological activities.

Animals↗
PubMed1993

Aluminium inhalation in sheep silicosis.

In prior studies, we and others have documented a significant reduction by surface chemistry modification in the biological activity of quartz. We further documented that aluminium lactate inhalation one month after quartz exposure significantly suppressed the silica-induced alveolitis, reduced the pathological process and decreased the retention of quartz in the lung tissue. In the present study, we evaluated the efficacy of aluminium inhalation in altering the silicosis process after disease was recognized by standard chest radiography. Twenty-four sheep were enrolled in the study. The 14 silica exposed sheep had an abnormal chest radiograph of the ILO category 1 or above after 3 years of 100 mg Minusil-5 in 100-ml saline intratracheal injections. Ten control sheep were exposed to saline intratracheal injections. All sheep were evaluated at 3-month intervals by chest radiography, lung function and lung lavage. At month 36 of the study, all 14 sheep had an abnormal chest radiograph while the radiographs of controls remained normal. The sheep with silicosis had significantly reduced lung functions and increased cellularity, phospholipids and hyaluronan. These changes persisted during the next 12 months without exposure or treatment. At month 48 and at monthly intervals after, for 12 months, aerosol inhalations were carried out with saline alone for control and seven silicotic sheep and with 100 mg of aluminium lactate in 10 ml saline generated with a Bird Mark 8 pressure ventilator for the other seven silicotic sheep. All sheep were evaluated at 3-month intervals by chest radiography, lung function and lung lavage.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗
PubMed1992

Ferruginous body counts in sputum as an index of past exposure to mineral fibres.

Previous work by our group among vermiculite miners exposed to fibrous tremolite demonstrated that asbestos body counts in sputum closely reflected intensity and duration of past exposure. In the present project sputum samples from nearly 600 volunteers from 11 cohorts of workers exposed to asbestos and other mineral fibres were found to contain much lower numbers of asbestos bodies than had been observed in vermiculite workers and these counts did not reliably reflect past levels of exposure. No evidence was found that occupational exposure to man-made mineral fibres led to any ferruginous body formation. Asbestos body counts appeared to differentiate between mesothelioma cases and controls and between levels of radiological asbestosis, but in both comparisons, based on small numbers, the power of discrimination was low. Substantial variation was found both in asbestos body and in macrophage counts in daily sampling of vermiculite workers but it was not sufficient to invalidate comparison between groups for epidemiological study. In individual subjects, however, little reliance can be put on results from a single sputum sample, particularly if negative.

Adult↗
PubMed1992

Pulmonary clearance of fibrous and angular SiC particulates in the sheep model of pneumoconiosis.

Both angular and fibrous SiC (carborundum) particulates can be emitted by SiC production operations. Carborundum pneumoconiosis is now recognized as an occupational lung disease with specific pathological features. These were previously reproduced in the sheep model of pneumoconiosis with fibrous SiC but not with angular SiC. To further document this question, the pulmonary retention in the sheep of the two morphological types was studied. Animals were injected in the tracheal lobe with equal mass (100 mg) of particulates prepared from SiC materials taken in the field. Particles were measured by analytical transmission electron microscopy in samples of bronchoalveolar lavage fluids (BAL) obtained at months 2, 4, 6 and 8 after the injection. They were also measured in samples of lung parenchyma obtained at month 8. Measurements in BAL and in lung samples both indicated a much lower retention for fibrous than for angular SiC. The retention rate in lung parenchyma at month 8 was 30 times lower for fibrous SiC. The half-life of decrease of concentrations was 3.4 times shorter for fibrous SiC. Other data in the literature support the notion that fine fibres are cleared more effectively than coarser angular particles.

Animals↗
PubMed1990

Lung dust analysis in the assessment of past exposure of man-made mineral fibre workers.

In the cohort of American MMMF workers reported by ENTERLINE et al. [Ann. occup. Hyg. 31, 625-656 (1987)] autopsies were recorded in 652 (13.5%) of 4840 deaths. Lung tissue samples were sought from all pathologists and obtained in 145 (22.2%), together with similar samples from 124 matched referents. Lung fibre counts by phase contrast microscopy were 60% higher (P less than 0.05) in workers than referents. Electron microscopy (ATEM) also showed more fibres of all kinds--MMMF, asbestos and other--but no convincing excess of any one type. Lung samples of only 26% of workers contained any MMMF, almost all siliceous in nature and in low concentration. There were too few cases of lung cancer (19) for any useful conclusion; however, in the plant with the highest lung cancer SMR (200), and a probable mesothelioma, amosite at greater than 1.0 fibres per micrograms (f micrograms-1) was found in four of six workers but in none of their matched referents. Although our findings contribute little to the interpretation of the results obtained by ENTERLINE et al. they indicate the potential value of tissue analyses in monitoring epidemiological studies of MMMF exposure.

Cohort Studies↗
PubMed1990

Mass, number and size of lung fibres in the pathogenesis of asbestosis in sheep.

After long-term asbestos inhalation, the lung tissue burden is much less for chrysotile (CHRY) than for crocidolite (CRO) exposure. Nonetheless CHRY does not appear to be less fibrogenic. To study mechanisms responsible for the low retention of CHRY and the relationships with fibrogenesis, 15 sheep received a single intratracheal injection of either CHRY or CRO. Exposures in 100 ml saline consisted of 100 mg of 1-micron latex beads for the five control sheep, 100 mg UICC CRO fibres for the five CRO sheep and 100 mg UICC B CHRY fibres for the five CHRY sheep. Bronchoalveolar lavage (BAL) was carried out at months 2, 4, 6 and 8 after exposure and necropsy at month 8. BAL and tissue samples were analysed for fibres by transmission electron microscopy. At month 2, mass concentration in BAL was 108 +/- 30 ng/ml for CRO and 0.6 +/- 0.1 ng/ml for CHRY. BAL CRO decreased afterward but BAL CHRY did not. The mass concentration in the lung at month 8 was 40.6 +/- 8.7 ng/mg dry tissue for CRO and 11.5 +/- 7.0 ng/mg for CHRY. BAL fibrogenic activity at month 8 assessed by macrophage fibronectin production was less than 0.2 ng/10(6) cells/24 h in control sheep, 5 +/- 2 in CRO sheep and 11 +/- 2 in CHRY sheep (P less than 0.05 CRO vs CHRY). Histologic score of tissue injury fibrosis was 0 in control sheep, 1.9 +/- 0.3 in CRO sheep and 2.8 +/- 0.1 in CHRY sheep (P less than 0.05). At necropsy, the number size distribution of fibres per microgram of tissue from the (CRO)/(CHRY) sheep was respectively: (127 +/- 54)/(15 +/- 14) for fibres less than 5 microns, (18 +/- 17)/(32 +/- 14) for fibres greater than 5 microns, (1.6 +/- 8)/(7 +/- 13) for fibres greater than 20 microns. This study documented that the low pulmonary retention of CHRY was largely related to the faster alveolar clearance rate of CHRY mass. Fibrogenicity of CHRY remained higher and appeared to be related at least in part to the preferential retention of long and very long CHRY fibres.

Animals↗
PubMed1990

Chrysotile asbestos exposures can produce an alveolitis with limited fibrosing activity in a subset of high fibre retainer sheep.

Inhalation of fibrogenic mineral dust may enhance fibronectin (Fn) production by alveolar macrophages and increase fibroblast growth activity (FGA) in lung lavage fluid. To investigate the relationship of these changes to fibre retention and the development of asbestosis, we exposed 15 sheep to 100 mg Canadian chrysotile fibres in 100 ml saline, and ten sheep to 100 ml saline only, at ten day intervals. The animals were studied at 3 month intervals. At month 18, ten sheep had abnormal chest radiograph (category greater than or equal to 1) (group B) and five had normal radiograph (category 0) (group A). Pulmonary function data indicated restrictive patterns of abnormalities in both groups, more severe in group B. Sheep in group A had bronchoalveolar lavage (BAL) cellularity and biochemistry comparable to controls; sheep in group B had significant increases in total BAL cells (x2), macrophages (x2), neutrophils (x4) and eosinophils (x3), increased BAL lactate dehydrogenase and Fn, but FGA and procollagen 3 comparable to controls. Fibre retention was significantly increased in all exposed sheep and 2.5 x higher in group B vs group A despite similar exposures (70 intratracheal, 100 mg chrysotile infusions). Enhanced fibre retention in group B preceded the appearance of disease. This study confirms our earlier observation linking individual susceptibility to development of alveolitis to individual dust burden and provides evidence that the excess of fibre retention can be observed before detectable disease. In addition, we report a chrysotile-induced early alveolitis with incompletely expressed fibrosing activity at the time of initial radiographic detection. The intensity of the alveolitis is related to the degree of fibre retention.

Animals↗
PubMed1989

Mesothelioma and asbestos fiber type. Evidence from lung tissue analyses.

Lung tissue samples from 78 cases from autopsy of mesothelioma in Canada, 1980 through 1984, and from matched referents were examined by optical and analytical transmission electron microscopic study. Concentrations of amosite, crocidolite, and tremolite fibers, and of typical asbestos bodies discriminated sharply between cases and referents. The distributions of chrysotile and anthophyllite/talc fibers and of all other natural and man-made inorganic fibers (greater than or equal to 8 microns) in the two series were quite similar. Relative risk was related to the concentration of long (greater than or equal to 8 microns) amphibole fibers with no additional information provided by shorter fibers. The proportion of long fibers was much higher for amphiboles than chrysotile and, except for chrysotile, systematically higher in cases than referents. Amphibole asbestos fibers could explain most mesothelioma cases in Canada and other inorganic fibers, including chrysotile, very few. Fibrous tremolite, contaminant of many industrial minerals including chrysotile, probably explained most cases in the Quebec mining region and perhaps 20% elsewhere.

Asbestos↗
PubMed1989

Carborundum pneumoconiosis. Fibers in the mineral activate macrophages to produce fibroblast growth factors and sustain the chronic inflammatory disease.

Carborundum is a synthetic abrasive manufactured through fusion of high grade silica sand and finely ground carbon in an electric furnace at 2,400 degrees C. It had been considered an inert dust until recently. Two recent epidemiologic studies in Quebec have documented an excess of interstitial lung disease in plant workers and some 30 workers have received workman compensation. Histopathologic lesions have been described in four of the workers. To further investigate the carborundum pneumoconiosis, nine groups of eight sheep were exposed once in the tracheal lobe to either 100 ml saline, 100 mg latex beads in 100 ml saline, 100 mg graphite in 100 ml saline, 100 mg carborundum particles in 100 ml saline, 100 mg ashed carborundum particles in 100 ml saline, 100 mg of quartz (Minusil-5) in 100 ml saline, 100 mg crocidolite fibers in 100 ml saline, 100 mg carborundum fibers in 100 ml saline, and 100 mg ashed carborundum fibers in 100 ml saline solutions. The animals had BAL at two-month intervals and autopsy at month 8. The BAL analyses of cellularity, cytotoxicity and fibrogenicity, in association to necropsy histopathology, documented that all particles except for quartz were inert. The two-carborundum fiber samples produced a similar sustained nodular fibrosing alveolitis and crocidolite asbestos fibers produced a peribronchiolar fibrosing alveolitis of comparable severity. Thus, the major bioactive dusts in the carborundum manufacturing process are quartz particles and the carborundum fibers generated in the process. The latter have fibrogenic activities comparable to asbestos fibers of similar size and are likely to contribute to the pathogenesis of the interstitial lung disease of carborundum workers.

Animals↗