Predicting the in vitro dissolution rate constant of mineral wool fibers from fiber composition.

OBJECTIVE: We developed predictive formulae for the in vitro dissolution rate constant kdis of acid-soluble synthetic vitreous fibers (SVF), paralleling our earlier work with glass wools, which are typically more soluble at neutral pH. Developing simple models for predicting the kdis of a fiber can allow prediction of in vivo behavior, aid fiber developers, and potentially reduce in vivo testing. METHODS: The kdis of several acid-soluble SVF were determined using high simulant fluid flow/fiber surface area (F/A) conditions via a single-fiber measurement system. Four fluids were employed, varying in base composition and citrate levels. Equations predicting the kdis were derived from fiber chemistry and dissolution measurements for two of the fluids. RESULTS: Testing of several fibers showed a ∼10× increase in the kdis when citrate was included in the simulant solution. Data from tests with Stefaniak's citrate-free Phagoloysosmal Simulant Fluid (PSF) yielded kdis values aligned with expectations from in vivo results, unlike results from citrate-containing modified Gamble's solution. Predictive equations relating fiber chemistry to kdis showed reasonable agreement between the measured and predicted values. CONCLUSIONS: Citrate inclusion in the solution under high F/A conditions significantly increased the measured kdis. This resulted in more biorelevant data being obtained using the PSF fluid with the high F/A method used. The developed predictive equations, sufficient for fiber development work, require refinement before a recommending their use in place of in vivo biopersistence testing. Significant fit improvements are possible through additional measurements under these experimental conditions.

The effect of a new formaldehyde-free binder on the dissolution rate of glass wool fibre in physiological saline solution.

The in-vitro dissolution rate of fibres is a good predictor of the in-vivo behavior and potential health effects of inhaled fibres. This study examines the effect of a new formaldehyde-free carbohydrate-polycarboxylic acid binder on the in-vitro dissolution rate of biosoluble glass fibres. Dissolution rate measurements in pH 7.4 physiological saline solution show that the presence of the binder on wool insulation glass fibres has no effect on their dissolution. There is no measurable difference between the dissolution rates of continuous draw fibres before and after binder was applied by dipping. Nor is there a measurable difference between the dissolution rates of a production glass wool sample with binder and that same sample after removal of the binder by low-temperature ashing. Morphological examination shows that swelling of the binder in the solution is at least partially responsible for the development of open channels around the glass-binder interface early in the dissolution. These channels allow fluid to reach the entire glass surface under the binder coating. There is no evidence of any delay in the dissolution rate as a result of the binder coating.

Do vitreous fibers break in the lung?

In order to determine whether breakage of long vitreous fibers in the lung could be responsible for removing significant numbers of these fibers, an intratracheal instillation study was done with a preparation consisting of mostly long fibers of two different types. Following instillation of both fibers, laboratory rats were sacrificed at 6 times up to 14 days. The NK (conventional borosilicate glass) fiber preparation had about 20% short fibers (length < or = 15 microm) initially, and fibers recovered from the lungs remained at that proportion for the entire 14 days. But the HT (a new rock or stone wool) fiber preparation, which had about 5% short fibers initially, jumped to about 50% short fibers at 2 days and remained at that proportion for the rest of the study. The appearance of many short HT fibers where there were few initially is conclusive evidence that these long fibers break, and it explains their rapid removal from the lung. Since the HT fibers dissolve rapidly at acid pH, but slowly at the near neutral pH of the extracellular lung fluid, it is likely that acid attack by phagocytic cells is causing the long fibers to dissolve and break. The long NK fibers dissolve rapidly at neutral pH but slowly at acid pH and thus appear to clear by more or less uniform dissolution without apparent breakage. The long fibers of these two kinds are removed rapidly at about the same rate, but by a different mechanism.

Translocation of inhaled ultrafine manganese oxide particles to the central nervous system.

BACKGROUND: Studies in monkeys with intranasally instilled gold ultrafine particles (UFPs; <100 nm) and in rats with inhaled carbon UFPs suggested that solid UFPs deposited in the nose travel along the olfactory nerve to the olfactory bulb. METHODS: To determine if olfactory translocation occurs for other solid metal UFPs and assess potential health effects, we exposed groups of rats to manganese (Mn) oxide UFPs (30 nm; approximately 500 microg/m(superscript)3(/superscript)) with either both nostrils patent or the right nostril occluded. We analyzed Mn in lung, liver, olfactory bulb, and other brain regions, and we performed gene and protein analyses. RESULTS: After 12 days of exposure with both nostrils patent, Mn concentrations in the olfactory bulb increased 3.5-fold, whereas lung Mn concentrations doubled; there were also increases in striatum, frontal cortex, and cerebellum. Lung lavage analysis showed no indications of lung inflammation, whereas increases in olfactory bulb tumor necrosis factor-alpha mRNA (approximately 8-fold) and protein (approximately 30-fold) were found after 11 days of exposure and, to a lesser degree, in other brain regions with increased Mn levels. Macrophage inflammatory protein-2, glial fibrillary acidic protein, and neuronal cell adhesion molecule mRNA were also increased in olfactory bulb. With the right nostril occluded for a 2-day exposure, Mn accumulated only in the left olfactory bulb. Solubilization of the Mn oxide UFPs was <1.5% per day. CONCLUSIONS: We conclude that the olfactory neuronal pathway is efficient for translocating inhaled Mn oxide as solid UFPs to the central nervous system and that this can result in inflammatory changes. We suggest that despite differences between human and rodent olfactory systems, this pathway is relevant in humans.

The role of fiber durability/biopersistence of silica-based synthetic vitreous fibers and their influence on toxicology.

This work summarizes what is known about the role of fiber durability/biopersistence of silica-based synthetic vitreous fibers (SVFs) and their influence on toxicology. The article describes the key processes leading from exposure to biological effect, including exposure, pulmonary deposition, clearance by various mechanisms, accumulation in the lung, and finally possible biological effects. The dose-dimension-durability paradigm is used to explain the key determinants of SVF toxicology. In particular, the key role played by the durability/biopersistence of long (>20microm) fibers is highlighted. Relevant literature on the prediction of in-vitro dissolution rates from chemical composition is summarized. Data from in-vitro and in-vivo durability/biopersistence tests show that these measures are highly correlated for long fibers. Both durability and biopersistence are correlated with the outcome of chronic inhalation bioassays. A schematic approach is presented for the design and testing of new SVFs with lower biopersistence.