In-vivo experimental model for silicosis : fisher 344, sprague dawley and wistar rat strains

The selection of an experimental model for silicosis requires a thorough understanding of a number of different pulmonary parameters specific to the animal that is to be used (e.g., clearance time, penetration curves, anatomical differences...), and of the sensitivity of the strains that are to be used. The pulmonary response of three rat strains (i.e., Fisher 344, Sprague Dawley, Wistar) to silica dust were compared using two different exposure methods: intra-tracheal injections and inhalation. The test periods lasted 3 months for injection and 6 and 12 months for inhalation. The histological study of the lung revealed a distinct nodular reaction among Sprague Dawley and Wistar strains. Intra-tracheal injections led to the development of fibrotic nodules among Wistar rats, whereas such silicotic nodules were infrequent among injected Fisher 344 rats, and almost absent when exposure was by inhalation. Sprague Dawley and Fisher 344 rats showed frequent thickening and metaplasia of the alveolar walls near the terminal bronchioles. This tendency was particularly pronounced among rats exposed by inhalation (especially among Fisher 344 rats). Evaluation of wet lung weight (i.e., hydroxyproline, lipid and silica lung contents) reveals an increase in the different parameters for Sprague Dawley rats relative to the other two strains, regardless of the type of exposure. It has thus been concluded that Wistar rats are the best experimental model for silicosis, as their pulmonary reaction is more characteristic than that of the other two strains

Pulmonary responses to silica dust : the influence of crystalline structures and physico-chemical properties

The inhalation of silica crystalline polymorphs leads to the development of pulmonary nodules that vary in extent and in fibrotic content. In this study, a single protocol was used to test different silica samples (i.e., 2 non-crystalline samples: one vitreous silica, one diatomaceous earth , 4 crystalline samples: one pure a-quartz ground in a wet atmosphere, one of the same quartz heated until it becomes oc-cristobalite and 2 cristobalites obtained by heating diatomaceous earth). Wistar rats received a single intra-tracheal injection of alveolar dust and were followed over a period of 3 months. The results were exploited using macroscopic examination (wet lung weight), histological examination and biochemical dosing (hydroxyproline, lipid, and silica content). The results showed that vitreous silica, diatomaceous earth, wet-ground quartz and both types of cristobalites are responsible to a greater or lesser extent for the pulmonary reaction typical of exposure to silica (i.e., nodules ); with different cellular and fibrotic surface areas for each sample. a-cristobalite (obtained from the wet-ground quartz heated to a very high temperature; 1,300 °C) leads to the formation of only small foreign-body granulomas. All crystalline minerals tested caused alveolar lipoproteinosis. It was thus concluded that the crystalline structure plays a less important role than the surface state in the formation of silicotic nodules

Possible Application of Urinary Analysis to Estimate Dissolution of Some Man-made Vitreous Fibers

International audienceA preliminary study at the Institut National de l'Environnement Industriel et des Risques (INERIS] examined the dissolution of three man-made vitreous fiber samples (glasswool, rockwool, glass microfibers: JM 100) after intraperitoneal injections in male Wistar rats. The chemical composition of the original fibers was determined by inductively coupled plasma spectrometry (ICP). The urine of the rats was collected at fixed times between day 1 and day 204, and the ICP was used to look for elements known to be present in the original fibers. At day 204, a piece of omentum was removed at autopsy, ashed and analyzed by energy dispersive X-ray analysis (EDXA) to identify the elements remaining in the fibers. Silicon and aluminium were retained in the fibers from all samples at day 204. Losses in calcium, sodium, magnesium, and sulfur were observed, but these elements were not studied in the urine samples because they are naturally present in relatively high concentrations in rat cells and biological fluids. Although there was a loss of zinc from the glass microfibers, no corresponding difference was observed between the zinc levels excreted by the treated animals and by the controls. Similarly, despite the loss of manganese from the rockwool fibers al day 204, none was detectable in the urine samples. Titanium, present at the 0.3% level in rockwool, was not detectable by EDXA at day 204, but small quantities were detected in the first 2 weeks in the urine samples of rats treated with rockwool. The barium content of the retained glass microfibers (JM 100) had decreased at day 204, and this element was detectable in the corresponding urine samples, It was considered that Ti and Ba could be suitable biomarkers of exposure to rockwool and glass microfibers (JM 100)

TNF as an exposure or risk marker among French coal miners in three different regions

Several studies have revealed the crucial role of the Tumor Necrosis Factor-a (TNF) in both the fibrosis induced by silica containing dusts and in the transition from coal workers simple pneumoconiosis (CWSP) to progressive massive fibrosis (PMF

Evaluation of Tumor-Necrosis-Factor-Alpha (TNF) as an exposure or risk marker in three French coal-mining regions

International audienceSeveral studies have shown the crucial role of the tumor necrosis factor-alpha (TNF) in the fibrosis induced by dusts containing silica and its role in the transition from simple pneumoconiosis (CWSP) to progressive massive fibrosis (PMF). To evaluate the nocivity of dust exposure among coal miners (n = 474) from different mining regions in France (e.g., Nord-Pas de Calais, Lorraine, and Provence), spontaneous and LPS or silica-induced TNF released by peripheral blood monocytes was quantified. The primary aim of this effort was to study the link between the prevalence of coal workers pneumoconiosis (CWP) and TNF release. TNF levels were significantly different between active miners from the three regions. However, after correction for age and region, TNF was found not to be related to dust exposure. Interestingly, a very low, homogeneous expression of TNF was observed in the group from Provence. These results are probably related to the absence of pneumoconiosis in this area. A positive relation between profusion and TNF release was found for all stimulants among retired miners with PMF. Although in retired miners TNF release was consistently higher, the design of the study does not allow this effect to be separated from that of age. Both silica and nonstimulated TNF release were found to increase with increasing radiological Symptoms; the opposite was found for LPS-induced release

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

International audienceThis 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 metalloendopeptidase 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