Toxicity of Fibers and Particles—report of the Workshop Held in Munich, Germany, 26–27 October 2000

Greim, Helmut; Borm, Paul; Schins, Roel P. F.; Donaldson, Ken; Driscoll, Kevin E.; Hartwig, A.; Kuempel, E.; Oberdörster, Günter; Speit, G.

doi:10.1080/089583701316941285

Cited by 110 publications

(42 citation statements)

References 27 publications

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“…asbestos) and man-made (e.g. bio-non-degradable glass) fibers are associated with increased risks of pulmonary fibrosis and cancer after prolonged exposures (Greim et al 2001). Several studies have shown pathological changes (such as granuloma, alveolitis, epithelial hyperplasia and fibrosis) in the lung following instillation or inhalation of cellulose fibres (Milton et al 1990;Hadley et al 1992;Tatrai et al 1995;Tatrai et al 1996;Muhle et al 1997;Adamis et al 1997).…”

Section: Introductionmentioning

confidence: 95%

“…Durability, a phenomenon related to the biopersistence of inhaled particles in the lung, is believed to be an important parameter in determining the pathogenicity of inhaled solid materials (Muhle et al 1995;Muhle et al 1997). Studies suggest that cellulose fibers have a long biopersistence at least in rat lungs and exposure to dust and fibres of various cellulose-based materials can provoke respiratory symptoms and cause airway diseases (Greim et al 2001;Kraus et al 2004;Kobayashi et al 2004;Ç öplü et al 2005). However, toxicity data from MFC is still lacking.…”

Section: Introductionmentioning

confidence: 97%

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Health and environmental safety aspects of friction grinding and spray drying of microfibrillated cellulose

et al. 2011

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Microfibrillated cellulose (MFC), also referred to as nanocellulose, is one of the most promising innovations for forest sector. MFC is produced by fibrillating the fibres under high compression and shear forces. In this study we evaluated the worker exposures to particles in air during grinding and spray drying of birch cellulose. Processing of MFC with either a friction grinder or a spray dryer did not cause significant exposure to particles during normal operation. Grinding generated small amount of particles, which were mostly removed by fume hood. Spray dryer leaked particles when duct valve was closed, but when correctly operated the exposure to particles was low or nonexistent. To assess the health effects of the produced MFC, mouse macrophages and human monocyte derived macrophages were exposed to MFC and the viability and cytokine profile of the cells were studied thereafter. No evidence of inflammatory effects or cytotoxicity on mouse and human macrophages was observed after 6 and 24 h exposure to the materials studied. The results of toxicity studies suggest that the friction ground MFC is not cytotoxic and does not cause any effects on inflammatory system in macrophages. In addition, environmental safety of MFC was studied with ecotoxicity test. Acute environmental toxicity assessed with kinetic luminescent bacteria test showed high NOEC values ([100 mg/l) for studied MFC. However, MFC disturbed Daphnia magna mobility mechanically when the test was performed according to the standard procedure.

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Section: Introductionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 97%

Health and environmental safety aspects of friction grinding and spray drying of microfibrillated cellulose

et al. 2011

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“…For example, the acute mortality due to inhalation of particulate matter may relate more to recent deposited mass, while morbidity observed over long durations in some ecological epidemiological studies may relate more to retained mass (U.S. EPA, 1996;Snipes et al, 1997). A recent workshop on fiber and particle toxicity recommended that species-specific toxicokinetic models should be used to predict particle clearance and retention in the lungs (Greim et al, 2001).…”

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confidence: 98%

Dosimetric Adjustments for Interspecies Extrapolation of Inhaled Poorly Soluble Particles (PSP)

Jarabek

Asgharian

Miller

2005

Inhalation Toxicology

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Direct calculation of delivered dose in the species of interest potentially affects the magnitude of an uncertainty factor needed to address extrapolation of laboratory animal data to equivalent human exposure scenarios, thereby improving the accuracy of human health risk estimates. Development of an inhalation reference concentration (RfC) typically involves extrapolation of an effect level observed in a laboratory animal exposure study to a level of exposure in humans that is not expected to result in an appreciable health risk. The default dose metric used for respiratory effects is the average deposited dose normalized by regional surface area. However, the most relevant dose metric is generally one that is most closely associated with the mode of action leading to the response. Critical factors in determining the best dose metric to characterize the dose-response relationship include the following: the nature of the biological response being examined; the magnitude, duration, and frequency of the intended exposure scenario; and the mechanisms by which the toxicants exert their effects. Dosimetry models provide mechanistic descriptions of these critical factors and can compute species-specific dose metrics. In this article, various dose metrics are postulated based on potential modes of action for poorly soluble particles (PSP). Dosimetry models are used to extrapolate the internal dose metric across species and to estimate the human equivalent concentration (HEC). Dosimetry models for the lower respiratory tract (LRT) of humans and rats are used to calculate deposition and retention using the principle of particle mass balance in the lower respiratory tract. Realistic asymmetric lung geometries using detailed morphometric measurements of the tracheobronchial (TB) airways in rats and humans are employed in model calculations. Various dose metrics are considered for the TB and pulmonary (P) regions. Because time is an explicit parameter incorporated in species-specific constants such as mucociliary clearance rates used in the models, the impact of the application of optimal model structures to refine adjustments and assumptions used in default risk assessment approaches to address exposure duration are discussed. HEC estimates were found for particles ranging in sizes that corresponded to existing toxicity studies of PSP (0.3 to 5 microm). A dose metric expressed as number of particles per biologically motivated normalization factors (e.g., number of ventilatory units, number of alveoli, and number of macrophages) was lower than the current default of mass normalized to regional surface area for either deposited or retained dose estimates. Retained dose estimates were lower than deposited dose estimates across all particle sizes evaluated. Dose metrics based on the deposited mass per unit area in small and large airways of the TB region indicate HECs of 1 to 5 times those of rats: that is, an equivalent exposure to humans which would achieve the same internal dose as in the rat would be 1 to 5 times greater. H...

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“…Mechanistic research (Greim et al, 2001;Eastes & Hadley, 2001) on fiber deposition, mode of action, and biopersistence suggests that chronic effects of fibers have dosimetric and mechanistic thresholds, so that nonlinear and threshold models (U.S. EPA, 1999) are the more appropriate alternatives when assessing risk from respirable glass fibers. Linear models such as the U.S. EPA default multistage with its linear confidence limits are therefore more likely to overestimate risk for glass fibers than are nonlinear models.…”

Section: General Findingsmentioning

confidence: 99%

Quantitative Risk Assessment of Durable Glass Fibers

Fayerweather

Eastes

Cereghini

et al. 2002

Inhalation Toxicology

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This article presents a quantitative risk assessment for the theoretical lifetime cancer risk from the manufacture and use of relatively durable synthetic glass fibers. More specifically, we estimate levels of exposure to respirable fibers or fiberlike structures of E-glass and C-glass that, assuming a working lifetime exposure, pose a theoretical lifetime cancer risk of not more than 1 per 100,000. For comparability with other risk assessments we define these levels as nonsignificant exposures. Nonsignificant exposure levels are estimated from (a) the Institute of Occupational Medicine (IOM) chronic rat inhalation bioassay of durable E-glass microfibers, and (b) the Research Consulting Company (RCC) chronic inhalation bioassay of durable refractory ceramic fibers (RCF). Best estimates of nonsignificant E-glass exposure exceed 0.05-0.13 fibers (or shards) per cubic centimeter (cm3) when calculated from the multistage nonthreshold model. Best estimates of nonsignificant C-glass exposure exceed 0.27-0.6 fibers/cm3. Estimates of nonsignificant exposure increase markedly for E- and C-glass when non-linear models are applied and rapidly exceed 1 fiber/cm3. Controlling durable fiber exposures to an 8-h time-weighted average of 0.05 fibers/cm3 will assure that the additional theoretical lifetime risk from working lifetime exposures to these durable fibers or shards is kept below the 1 per 100,000 level. Measured airborne exposures to respirable, durable glass fibers (or shards) in glass fiber manufacturing and fabrication operations were compared with the nonsignificant exposure estimates described. Sampling results for B-sized respirable E-glass fibers at facilities that manufacture or fabricate small-diameter continuous-filament products, from those that manufacture respirable E-glass shards from PERG (process to efficiently recycle glass), from milled fiber operations, and from respirable C-glass shards from Flakeglass operations indicate very low median exposures of 0, 0.0002, 0.007, 0.008, and 0.0025 fibers (or shards)/cm3, respectively using the NIOSH 7400 Method ("B" rules). Durable glass fiber exposures for various applications must be well characterized to ensure that they are kept below nonsignificant levels (e.g., 0.05 fibers/cm3) as defined in this risk assessment.

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Toxicity of Fibers and Particles—report of the Workshop Held in Munich, Germany, 26–27 October 2000

Cited by 110 publications

References 27 publications

Health and environmental safety aspects of friction grinding and spray drying of microfibrillated cellulose

Health and environmental safety aspects of friction grinding and spray drying of microfibrillated cellulose

Dosimetric Adjustments for Interspecies Extrapolation of Inhaled Poorly Soluble Particles (PSP)

Quantitative Risk Assessment of Durable Glass Fibers

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