Short Term Effect of Silicon Carbide Whisker to the Rat Lung.

Journal of Occupational Health

et al. 2003

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Clearance of Deposited Silicon Carbide Whisker from Rat Lungs Inhaled during a 4‐Week Exposure: Izumi Akiyama, et al. Department of Environmental Health Engineering, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health— Pulmonary deposition and the clearance of deposited fiber particles from lungs are key determinant factors in assessing potential carcinogenicity and fibrogenicity. Forty‐two Wistar male rats (9 wk old) were exposed to silicon carbide whisker (SiCW) for 6 h/d, 5 d/wk for 4 wk. The mass median aerodynamic diameter was 2.5 µm as detected by an Andersen sampler, and the geometric mean fiber diameter and length determined by a scanning electron microscope were 0.4 and 2.2 µm, respectively. The daily average exposure concentrations were 10.4 ± 0.5 mg/m3 (214 ± 31 fibers/ ml) during the exposure period. The rats were sacrificed after 3 d, 2 wk, 1, 2, 3, 6 and 12 months after 4‐wk exposure. At the time of sacrifice, the wet lung weights and the deposited SiCW amounts in the lungs were measured by an X ray reference method. The amount of SiCW deposited was 0.60 ± 0.09 mg 3 d after a 4‐wk exposure. The apparent deposition fraction was 4.8 ± 0.7 (%). During the clearance period, the amount of SiCW deposited in the rat lungs decreased exponentially with the increasing duration of the clearance period. The biological half time in the onecompartment model was determined to be 4.0 months which is similar to the values for glass fiber, potassium titanate whisker and aluminium‐silicate ceramic fiber under similar exposure conditions.

Section: Clearance Of the Deposited Sicw In The Rat Lungssupporting

confidence: 92%

Clearance of Deposited Silicon Carbide Whisker from Rat Lungs Inhaled during a 4‐Week Exposure

Akiyama

Ogami

Journal of Occupational Health

et al. 2003

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“…The results were then categorized into four grades and the score was determined. (Ogami et al, 2001).…”

Section: Morphological Proceduresmentioning

confidence: 95%

Patterns of Histopathological Change Determined by the Point Counting Method and Its Application for the Hazard Assessment of Respirable Dust

Ogami

Morimoto

et al. 2004

Inhalation Toxicology

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We evaluate the morphometric point counting method (PCM) for qualitatively analyzing pulmonary inflammation and collagen deposits (i.e., fibrosis) in the assessment of the biological hazards of inhaled respirable particles at a realistic dose comparable to that of exposure in the work environment. Rats were exposed by intratracheal instillation to a 2-mg dose, which is close to the estimated overdose at which macrophage clearance is impared, of each of 3 kinds of particulate matter: crystalline silica, crocidolite asbestos, and titanium dioxide. The lung tissue was evaluated at 3 days, 1 wk, and 1, 3, and 6 mo after exposure. Digital images taken of the lung tissue after processing and staining of the lung sections were examined by the PCM under light microscopy. Evidence of inflammation along with progressive inflammatory changes occurred with crystalline silica and crocidolite, which are well-known hazardous particle types. In contrast, lung tissue from rats exposed to titanium dioxide particles demonstrated a decreasing pattern of histopathological change with increasing retention time. Differences in repair patterns of TiO(2) versus crocidolite and silica following the 2-mg dose exposure suggest that the PCM scoring system may be a useful and sensitive tool for qualitatively evaluating the biological hazards of new particle types, for which no toxicological information exists for low-dose exposure, by using the results from assessment of fibrogenic particle types (such as crocidolite and crystalline silica) as well as particle types with low toxicity (such as TiO(2)) as reference points.

“…In our previous study we reported that both inflammation and fibrosis were non-progressive in a SiCW intratracheal-instillation rat model 14) . It has been reported that surfactant has the ability to reduce dynamic surface tension 6,7) .…”

Section: Discussionmentioning

confidence: 99%

Gene Expression of Surfactant Protein‐A and Thyroid Transcription Factor‐1 in Lungs of Rats Exposed to Silicon‐Carbide Whisker in vivo

Morimoto

Ding

Journal of Occupational Health

et al. 2003

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No clear tendency to the expression of SP-C was observed, but the patterns of expression of TTF-1 and SP-A were similar. These data suggest that SP-A and TTF-1 are associated with not only the acute phase but also the chronic phase in lungs exposed to SiCW. As occupational and environmental inhalation exposure to asbestos causes pulmonary fibrosis 1) , a number of manmade mineral fibers (MMMFs) have been developed as a substitute, but, because of their similar physiochemical properties, MMMFs are thought to have adverse biological effects similar to those of asbestos 2) . Animal studies have shown that silicon carbide whisker (SiCW), which is used in abrasive and refractory materials, and the production of parts for electronic equipment, cause fibrosis 3,4) , suggesting that SiCW might have a fibrogenic potential.Surfactant protein 5) produced by mainly type II alveolar epithelial cells acts as a control tower responsible for guiding the secretion and re-uptake of phospholipid which decreases alveolar surface tension, and through the prevention of alveolar collapse, these are thought to play contributory roles in preventing the progress of fibrotic processes 6,7) . Decreases in the levels of SP-A and SP-C mRNA have been reported to occur in the bronchoalveolar lavage fluid (BALF) of patients with idiopathic pulmonary fibrosis 5,8) , and SP-A is thought to be a good biomarker of lung injury and pulmonary fibrotic activity.Furthermore, thyroid transcription factor-1 (TTF-1) 9) , a common transcription factor of SP-A and SP-C mRNA, is involved in tissue-specific gene expression of epithelial (SiCW), an asbestos substitute, produces pulmonary fibrotic changes, suggesting that SICW might have a fibrogenic potential. It is thought that surfactant protein is a good biomarker of lung injury and pulmonary fibrotic activity. In order to explore whether or not surfactant protein is associated with lung disorder through exposure to SiCW, we examined the expression of SP-A, SP-C and thyroid transcription factor-1 (TTF-1), a common transcription factor of SP-A and SP-C mRNA in lungs exposed to SiCW. Male Wistar rats were administered 2 mg or 10 mg of SiCW suspended in saline by a single intratracheal instillation, and were sacrificed at 3 d, 1 wk, 1 month, 3 months and 6 months after the intratracheal instillation. RNA was subsequently extracted from the lungs, and expression of SP-A, SP-C and TTF-1 mRNA from the lungs was observed by reverse transcriptionpolymerase chain reaction (RT-PCR). Exposure to 2 mg of SiCW showed a decrease in mRNA of SP-A and TTF-1 at 6 months, but exposure to 10 mg of SiCW showed decreased levels of SP-A and TTF-1 mRNA at 3 d and 6 months. On the other hand, 2 mg of SiCW increased the level of SP-C mRNA from 3 d to 3 months, and 10 mg of SiCW decreased the levels of SP-C mRNA in the rat lungs at 3 d, 1 month and 6 months.