Biopersistence of Man-Made Vitreous Fibers and Crocidolite Asbestos in the Rat Lung Following Inhalation

doi:10.1006/faat.1996.0031

Fundamental and Applied Toxicology

Volume 29, Issue 2, February 1996, Pages 267-279

Fundamental and Appl...

https://doi.org/10.1006/faat.1996.0031 Get rights and content

Abstract

This study investigated possible relationships between fiber biopersistence in the lung and previously observed differences in pulmonary toxicity between asbestos and man-made vitreous fibers (MMVF) following inhalation exposure. Fischer 344/N rats were exposed nose only, 6 hr/day for 5 days to 30 mg/m³MMVF (two fiberglass compositions, rock wool, or slag wool) or to 10 mg/m³crocidolite asbestos. At eight time points up to 1 year postexposure, lung fiber burdens were analyzed for number/lung and bivariate dimensions using scanning electron microscopy (SEM) and for chemical composition using SEM energy dispersive spectroscopy. After 365 days, >95% of long (>20 μm) MMVFs had disappeared from the lung compared to only 17% of long crocidolite fibers. Longer MMVFs disappeared more rapidly than short MMVFs, suggesting that long fibers were dissolving or breaking. Mean diameters and lengths of the MMVFs decreased with time, while the mean diameter of crocidolite remained unchanged and its mean length showed an apparent increase, probably related to macrophage-mediated clearance of short fibers. Leaching of oxides occurred in the fibrous glasses and slag wool and correlated with morphological changes in the fibers over time. No chemical or morphological changes were observed in crocidolite fibers. These changes in MMVF number, chemistry, and morphology over time in lung tissue compared to crocidolite asbestos demonstrate the relatively low biological persistence of some MMVFs in the lung and may explain why these MMVFs are not tumorigenic in rats, even after chronic exposure at high concentrations.

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Stone wool fiber materials are commonly used for thermal and acoustic insulation, horticulture and filler purposes. Biosolubility of the stone wool fiber (SWF) materials accessed through acellular in vitro dissolution tests can potentially be used in future as an indicator of fiber biopersistence in vivo. To correlate acellular in vitro studies with in vivo and epidemiological investigations, not only a robust dissolution procedure is needed, but fundamental understanding of fiber behavior during sample preparation and dissolution is required. We investigated the influence of heat treatment procedure for binder removal on the SWF iron oxidation state as well as on the SWF dissolution behavior in simulant lung fluids (with and without complexing agents). We used heat treatments at 450 °C for 5 min and 590 °C for 1 h. Both procedures resulted in complete binder removal from the SWF. Changes of iron oxidation state were moderate if binder was removed at 450 °C for 5 min, and there were no substantial changes of SWF’s dissolution behavior in all investigated fluids after this heat treatment. In contrast, if binder was removed at 590 °C for 1 h, complete Fe(II) oxidation to Fe(III) was observed and significant increase of dissolution was shown in fluids without complexing agent (citrate). PHREEQC solution speciation modeling showed that in this case, released Fe(III) may form ferrihydrite precipitate in the solution. Precipitation of ferrihydrite solid phase leads to removal of iron cations from the solution, thus shifting reaction towards the dissolution products and increasing total mass loss of fiber samples. This effect is not observed for heat treated fibers if citrate is present in the fluid, because Fe(III) binds with citrate and remains mobile in the solution. Therefore, for developing the most accurate SWF in vitro acellular biosolubility test, SWF heat treatment for binder removal is not recommended in combination with dissolution testing in fluids without citrate as a complexing agent.
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Relationships among asbestos exposure, lung burden, and mesothelioma risks have been previously evaluated, but it would be useful to validate published epidemiological observations with a mathematical model describing deposition and elimination of various mineral types of fibers.
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In spite of potential limitations, mechanistical modelling of asbestos exposure can serve as an effective tool for risk assessment purposes.
The dissolution of stone wool fibers with sugar-based binder and oil in different synthetic lung fluids
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Citation Excerpt :
Nevertheless, it is important to improve in vitro mineral wool dissolution tests for better correlation with in vivo results (Bulsari et al., 2007). The dissolution of mineral wool fibers in vitro is often studied using flow-through experimental setups on fiber samples without organic binder (Christensen et al., 1994; Eastes et al., 2007; Guldberg et al., 1998, 2000, 2002, Hesterberg et al., 1994, 1996, 1998; Kamstrup et al., 1998; Steenberg et al., 2001). The choice of the liquid for in vitro dissolution tests should be justified based on the knowledge about dissolution mechanisms in each fluid.
The biopersistence of fiber materials is one of the cornerstones in estimating potential risk to human health upon inhalation. To connect epidemiological and in vivo investigations with in vitro studies, reliable and robust methods of fiber biopersistence determination and understanding of fiber dissolution mechanism are required. We investigated dissolution properties of oil treated stone wool fibers with and without sugar-based binder (SBB) at 37 °C in the liquids representing macrophages intracellular conditions (pH 4.5). Conditions varied from batch to flow of different rates. Fiber morphology and surface chemistry changes caused by dissolution were monitored with scanning electron microscopy and time-of-flight secondary ion mass spectrometry mapping. Stone wool fiber dissolution rate depends on liquid composition (presence of ligands, such as citrate), pH, reaction products transport and fibers wetting properties. The dissolution rate decreases when: 1) citrate is consumed by the reaction with the released Al cations; 2) the pH increases during a reaction in poorly buffered solutions; 3) the dissolution products are accumulated; 4) fibers are not fully wetted with the fluid. Presence of SBB has no influence on dissolution rate if fiber material was wetted prior to dissolution experiment to avoid poorly wetted fiber agglomerates formation in the synthetic lung fluids.
Evaluation of the exposure, dose-response and fate in the lung and pleura of chrysotile-containing brake dust compared to TiO<inf>2</inf>, chrysotile, crocidolite or amosite asbestos in a 90-day quantitative inhalation toxicology study – Interim results Part 1: Experimental design, aerosol exposure, lung burdens and BAL
2020, Toxicology and Applied Pharmacology
This 90-day repeated-dose inhalation toxicology study of brake-dust (BD) (brakes manufactured with chrysotile) in rats provides a comprehensive understanding of the biokinetics and potential toxicology in the lung and pleura. Exposure was 6 h/d, 5d/wk., 13wks followed by lifetime observation (~20 % survival). Control groups included a particle control (TiO₂), chrysotile, commercial crocidolite and amosite asbestos.
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The typical insulation rock, slag and glass wool fibers are high volume materials. Current exposure levels in industry (generally ≤ 1 fiber/cm³ with a median diameter ∼1 μm and length ≥10 μm) are not considered carcinogenic or causing other types of severe lung effects. However, epidemiological studies are not informative on effects in humans at fiber levels >1 fiber/cm³. Effects may be inferred from valid rat studies, conducted with rat respirable fibers (diameter ≤ 1.5 μm). Therefore, we estimate delivery and deposition in human and rat airways of the industrial fibers. The deposition fractions in humans head regions by nasal (∼0.20) and by mouth breathing (≤0.08) are lower than in rats (0.50). The delivered dose into the lungs per unit lung surface area during a 1-day exposure at a similar air concentration is estimated to be about two times higher in humans than in rats. The deposition fractions in human lungs by nasal (∼0.20) and by mouth breathing (∼0.40) are higher than in rats (∼0.04). The human lung deposition may be up to three times by nasal breathing and up to six times higher by oral breathing than in rats, qualifying assessment factor setting for deposition.
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Non-occupational, environmental and unintentional exposure to fibrous tremolite, one of the most widespread naturally occurring asbestos, represents a potentially significant geological risk in several parts of the world. The toxicity of amphibole asbestos is commonly related to iron content and oxidation state, but information available on surface iron topochemistry and amphibole alteration mechanism is still rather poor. With the aim to shed a light on this mechanism, two tremolite samples, one from Italy (Castelluccio) and one from USA (Maryland), immersed in a buffer solution (pH 7.4) with H₂O₂ were characterized by a multi-technique approach. X-ray photoelectron spectroscopy (XPS) and high resolution–transmission electron microscopy (HR-TEM) were used to investigate the surface chemistry of the incubated samples and to detect structural modifications of the fibres, while inductively coupled plasma optical emission spectrometry (ICP-OES) was used to determine the concentration of dissolved elements.
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Regular ArticleBiopersistence of Man-Made Vitreous Fibers and Crocidolite Asbestos in the Rat Lung Following Inhalation

Abstract

Regular Article
Biopersistence of Man-Made Vitreous Fibers and Crocidolite Asbestos in the Rat Lung Following Inhalation