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Tina M Sager - One of the best experts on this subject based on the ideXlab platform.
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surface area of particle administered versus mass in determining the Pulmonary Toxicity of ultrafine and fine carbon black comparison to ultrafine titanium dioxide
Particle and Fibre Toxicology, 2009Co-Authors: Tina M Sager, Vincent CastranovaAbstract:Nanoparticles are characterized by having a high surface area per mass. Particulate surface area has been reported to play an important role in determining the biological activity of nanoparticles. However, recent reports have questioned this relationship. This study was conducted to determine whether mass of particles or surface area of particles is the more appropriate dose metric for Pulmonary Toxicity studies. In this study, rats were exposed by intratracheal instillation to various doses of ultrafine and fine carbon black. At 1, 7, or 42 days post-exposure, inflammatory and cytotoxic potential of each particle type was compared on both a mass dosage (mg/rat) as well as an equal surface area dosage (cm2 of particles per cm2 of alveolar epithelium). In an additional study, the Pulmonary responses to instillation of ultrafine carbon black were compared to equivalent particle surface area doses of ultrafine titanium dioxide. Ultrafine carbon black particles caused a dose dependent but transient inflammatory and cytotoxic response. On a mass basis, these responses were significantly (65 fold) greater than those for fine sized carbon black. However, when doses were equalized based on surface area of particles given, the ultrafine carbon black particles were only slightly (non-significantly) more inflammogenic and cytotoxic compared to the fine sized carbon black. At one day post-exposure, inflammatory potencies of the ultrafine carbon black and ultrafine titanium dioxide particles were similar. However, while the Pulmonary reaction to ultrafine carbon black resolved with time, the inflammatory effects of ultrafine titanium dioxide were more persistent over a 42 day post-exposure period. These results indicate that for low Toxicity low solubility materials, surface area of particles administered rather than mass burden of particles may be a more appropriate dose metric for Pulmonary Toxicity studies. In addition, ultrafine titanium dioxide appears to be more bioactive than ultrafine carbon black on an equivalent surface area of particles delivered basis.
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surface area of particle administered versus mass in determining the Pulmonary Toxicity of ultrafine and fine carbon black comparison to ultrafine titanium dioxide
Particle and Fibre Toxicology, 2009Co-Authors: Tina M Sager, Vincent CastranovaAbstract:Background Nanoparticles are characterized by having a high surface area per mass. Particulate surface area has been reported to play an important role in determining the biological activity of nanoparticles. However, recent reports have questioned this relationship. This study was conducted to determine whether mass of particles or surface area of particles is the more appropriate dose metric for Pulmonary Toxicity studies. In this study, rats were exposed by intratracheal instillation to various doses of ultrafine and fine carbon black. At 1, 7, or 42 days post-exposure, inflammatory and cytotoxic potential of each particle type was compared on both a mass dosage (mg/rat) as well as an equal surface area dosage (cm2 of particles per cm2 of alveolar epithelium). In an additional study, the Pulmonary responses to instillation of ultrafine carbon black were compared to equivalent particle surface area doses of ultrafine titanium dioxide.
Vincent Castranova - One of the best experts on this subject based on the ideXlab platform.
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surface area of particle administered versus mass in determining the Pulmonary Toxicity of ultrafine and fine carbon black comparison to ultrafine titanium dioxide
Particle and Fibre Toxicology, 2009Co-Authors: Tina M Sager, Vincent CastranovaAbstract:Background Nanoparticles are characterized by having a high surface area per mass. Particulate surface area has been reported to play an important role in determining the biological activity of nanoparticles. However, recent reports have questioned this relationship. This study was conducted to determine whether mass of particles or surface area of particles is the more appropriate dose metric for Pulmonary Toxicity studies. In this study, rats were exposed by intratracheal instillation to various doses of ultrafine and fine carbon black. At 1, 7, or 42 days post-exposure, inflammatory and cytotoxic potential of each particle type was compared on both a mass dosage (mg/rat) as well as an equal surface area dosage (cm2 of particles per cm2 of alveolar epithelium). In an additional study, the Pulmonary responses to instillation of ultrafine carbon black were compared to equivalent particle surface area doses of ultrafine titanium dioxide.
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surface area of particle administered versus mass in determining the Pulmonary Toxicity of ultrafine and fine carbon black comparison to ultrafine titanium dioxide
Particle and Fibre Toxicology, 2009Co-Authors: Tina M Sager, Vincent CastranovaAbstract:Nanoparticles are characterized by having a high surface area per mass. Particulate surface area has been reported to play an important role in determining the biological activity of nanoparticles. However, recent reports have questioned this relationship. This study was conducted to determine whether mass of particles or surface area of particles is the more appropriate dose metric for Pulmonary Toxicity studies. In this study, rats were exposed by intratracheal instillation to various doses of ultrafine and fine carbon black. At 1, 7, or 42 days post-exposure, inflammatory and cytotoxic potential of each particle type was compared on both a mass dosage (mg/rat) as well as an equal surface area dosage (cm2 of particles per cm2 of alveolar epithelium). In an additional study, the Pulmonary responses to instillation of ultrafine carbon black were compared to equivalent particle surface area doses of ultrafine titanium dioxide. Ultrafine carbon black particles caused a dose dependent but transient inflammatory and cytotoxic response. On a mass basis, these responses were significantly (65 fold) greater than those for fine sized carbon black. However, when doses were equalized based on surface area of particles given, the ultrafine carbon black particles were only slightly (non-significantly) more inflammogenic and cytotoxic compared to the fine sized carbon black. At one day post-exposure, inflammatory potencies of the ultrafine carbon black and ultrafine titanium dioxide particles were similar. However, while the Pulmonary reaction to ultrafine carbon black resolved with time, the inflammatory effects of ultrafine titanium dioxide were more persistent over a 42 day post-exposure period. These results indicate that for low Toxicity low solubility materials, surface area of particles administered rather than mass burden of particles may be a more appropriate dose metric for Pulmonary Toxicity studies. In addition, ultrafine titanium dioxide appears to be more bioactive than ultrafine carbon black on an equivalent surface area of particles delivered basis.
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Comparative Pulmonary Toxicity of blasting sand and five substitute abrasive blasting agents.
Journal of Toxicology and Environmental Health, 2002Co-Authors: Dale W. Porter, Mark Greskevitch, Douglas P. Landsittel, Victor A Robinson, Ann F Hubbs, Lori A Battelli, Mark Barger, William Jones, Vincent CastranovaAbstract:Blasting sand is used for abrasive blasting, but its inhalation is associated with Pulmonary inflammation and fibrosis. Consequently, safer substitute materials for blasting sand are needed. In a previous study from this laboratory, the comparative Pulmonary Toxicity of five abrasive blasting substitutes and blasting sand was reported. In this study, the Pulmonary Toxicity of blasting sand was compared to five additional abrasive blasting substitutes: steel grit, copper slag, nickel slag, crushed glass, and olivine. Exposed rats received by intratracheal instillation 10 mg of respirable-size particles of blasting sand or an abrasive blasting substitute, while controls were instilled with vehicle. Pulmonary inflammation, damage, and fibrosis were examined 28 d postexposure. Pulmonary inflammation was monitored by determining bronchoalveolar lavage polymorphonuclear cell counts and alveolar macrophage activation by chemiluminescence. Pulmonary damage was assessed by acellular bronchoalveolar (BAL) fluid ser...
Jurgen Pauluhn - One of the best experts on this subject based on the ideXlab platform.
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retrospective analysis of 4 week inhalation studies in rats with focus on fate and Pulmonary Toxicity of two nanosized aluminum oxyhydroxides boehmite and pigment grade iron oxide magnetite the key metric of dose is particle mass and not particle sur
Toxicology, 2009Co-Authors: Jurgen PauluhnAbstract:This paper compares the Pulmonary toxicokinetics and toxicodynamics of three different types of poorly soluble dusts examined in repeated rat inhalation bioassays (6 h/day, 5 days/week, 4 weeks). In these studies the fate of particles was studied during a 3–6-month postexposure period. This retrospective analysis included two types of aluminum oxyhydroxides (AlOOH, boehmite), high purity calcined, and agglomerated nanosized aluminas of very low solubility with primary isometric particles of 10 or 40 nm, and synthetic iron oxide black (Fe3O4 pigment grade). Three metrics of dose (actual mass concentration, surface area concentration, mass-based lung burden) were compared with Pulmonary Toxicity characterized by bronchoalveolar lavage. The results of this analysis provide strong evidence that Pulmonary Toxicity (inflammation) corresponds best with the mass-based cumulative lung exposure dose. The inhalation study with a MMAD of ≈0.5 μm yielded a higher Pulmonary dose than MMADs in the range of 1–2 μm, a range most commonly used in repeated exposure inhalation studies. Hence, a key premise for the dosimetric adjustment across species is that comparable lung tissue doses should cause comparable effects. From that perspective, the determination of mass-based Pulmonary lung burdens appears to be amongst the most important and critical nominator of dose and dose-related Pulmonary Toxicity.
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Pulmonary Toxicity and fate of agglomerated 10 and 40 nm aluminum oxyhydroxides following 4 week inhalation exposure of rats toxic effects are determined by agglomerated not primary particle size
Toxicological Sciences, 2009Co-Authors: Jurgen PauluhnAbstract:Inhaled polydisperse micronsized agglomerated particulates composed of nanosized primary particles may exert their Pulmonary Toxicity in either form, depending on whether these tightly associated structures are disintegrated within the biological system or not. This hypothesis was tested in a rat bioassay using two calcined aluminum oxyhydroxides (AlOOH) consisting of primary particles in the range of 10-40 nm. Male Wistar rats were nose-only exposed to 0.4, 3, and 28 mg/m(3) in two 4-week (6 h/day, 5 days/week) inhalation studies followed by a 3-month postexposure period. The respective mass median aerodynamic diameter (MMAD) of agglomerated particles in inhalation chambers was 1.7 and 0.6 mum. At serial sacrifices, Pulmonary Toxicity was characterized by bronchoalveolar lavage (BAL) and histopathology. The retention kinetics of aluminum (Al) was determined in lung tissue, BAL cells, and selected extraPulmonary organs, including lung-associated lymph nodes (LALNs). Significant changes in BAL, lung, and LALN weights occurred at 28 mg/m(3). Histopathology revealed alveolar macrophages with enlarged and foamy appearance, increased epithelial cells, inflammatory cells, and focal septal thickening. The determination of aluminum in lung tissue shows that the cumulative lung dose was higher following exposure to AlOOH-40 nm/MMAD-0.6 mum than to AlOOH-10 nm/MMAD-1.7 mum, despite identical exposure concentrations. The associated Pulmonary inflammatory response appears to be principally dependent on the agglomerated rather than primary particle size. Despite high lung burdens, conclusively increased extraPulmonary organ burdens did not occur at any exposure concentration and postexposure time point. Particle-induced Pulmonary inflammation was restricted to cumulative doses exceeding approximately 1 mg AlOOH/g lung following 4-week exposure at 28 mg/m(3). It is concluded that the Pulmonary Toxicity of nanosized, agglomerated AlOOH particles appears to be determined by the size of agglomerated rather than primary particles, whereas the clearance half-time of particles appears to increase with decreased primary particle size. However, in regard to toxicokinetics, this outcome is highly contingent upon the total lung burden and especially whether overloading or non-overloading conditions were attained or not. In order to reliably demonstrate retention-related different characteristics in Toxicity and fate of poorly soluble (nano)particles postexposure periods of at least 3 months appear to be indispensible.
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Pulmonary Toxicity and fate of agglomerated 10 and 40 nm aluminum oxyhydroxides following 4 week inhalation exposure of rats toxic effects are determined by agglomerated not primary particle size
Toxicological Sciences, 2009Co-Authors: Jurgen PauluhnAbstract:Inhaled polydisperse micronsized agglomerated particulates composed of nanosized primary particles may exert their Pulmonary Toxicity in either form, depending on whether these tightly associated structures are disintegrated within the biological system or not. This hypothesis was tested in a rat bioassay using two calcined aluminum oxyhydroxides (AlOOH) consisting of primary particles in the range of 10–40 nm. Male Wistar rats were nose-only exposed to 0.4, 3, and 28 mg/m 3 in two 4-week (6 h/day, 5 days/week) inhalation studies followed by a 3-month postexposure period. The respective mass median aerodynamic diameter (MMAD) of agglomerated particles in inhalation chambers was 1.7 and 0.6 mm. At serial sacrifices, Pulmonary Toxicity was characterized by bronchoalveolar lavage (BAL) and histopathology. The retention kinetics of aluminum (Al) was determined in lung tissue, BAL cells, and selected extraPulmonary organs, including lung-associated lymph nodes (LALNs). Significant changes in BAL, lung, and LALN weights occurred at 28 mg/ m 3 . Histopathology revealed alveolar macrophages with enlarged and foamy appearance, increased epithelial cells, inflammatory cells, and focal septal thickening. The determination of aluminum in lung tissue shows that the cumulative lung dose was higher following exposure to AlOOH-40 nm/MMAD-0.6 mm than to AlOOH-10 nm/MMAD-1.7 mm, despite identical exposure concentrations. The associated Pulmonary inflammatory response appears to be principally dependent on the agglomerated rather than primary particle size. Despite high lung burdens, conclusively increased extraPulmonary organ burdens did not occur at any exposure concentration and postexposure time point. Particleinduced Pulmonary inflammation was restricted to cumulative doses exceeding approximately 1 mg AlOOH/g lung following 4week exposure at 28 mg/m 3 . It is concluded that the Pulmonary Toxicity of nanosized, agglomerated AlOOH particles appears to be determined by the size of agglomerated rather than primary particles, whereas the clearance half-time of particles appears to increase with decreased primary particle size. However, in regard to toxicokinetics, this outcome is highly contingent upon the total lung burden and especially whether overloading or nonoverloading conditions were attained or not. In order to reliably
T R Webb - One of the best experts on this subject based on the ideXlab platform.
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comparative Pulmonary Toxicity inhalation and instillation studies with different tio2 particle formulations impact of surface treatments on particle Toxicity
Toxicological Sciences, 2005Co-Authors: David B. Warheit, T R Webb, William J Brock, K P Lee, Kenneth L. ReedAbstract:Most pigment-grade titanium dioxide (TiO(2)) samples that have been tested in Pulmonary Toxicity tests have been of a generic variety-i.e., generally either uncoated particles or TiO(2) particles containing slightly hydrophilic surface treatments/coatings (i.e., base TiO(2)). The objectives of these studies were to assess in rats, the Pulmonary Toxicity of inhaled or intratracheally instilled TiO(2) particle formulations with various surface treatments, ranging from 0-6% alumina (Al(2)O(3)) or alumina and 0-11% amorphous silica (SiO(2)). The Pulmonary effects induced by TiO(2) particles with different surface treatments were compared to reference base TiO(2) particles and controls. In the first study, groups of rats were exposed to high exposure (dose) concentrations of TiO(2) particle formulations for 4 weeks at aerosol concentrations ranging from 1130-1300 mg/m(3) and lung tissues were evaluated by histopathology immediately after exposure, as well as at 2 weeks and 3, 6, and 12 months postexposure. In the second study, groups of rats were intratracheally instilled with nearly identical TiO(2) particle formulations (when compared to the inhalation study) at doses of 2 and 10 mg/kg. Subsequently, the lungs of saline-instilled and TiO(2)-exposed rats were assessed using both bronchoalveolar (BAL) biomarkers and by histopathology/cell proliferation assessment of lung tissues at 24 h, 1 week, 1 and 3 months postexposure. The results from these studies demonstrated that for both inhalation and instillation, only the TiO(2) particle formulations with the largest components of both alumina and amorphous silica surface treatments produced mildly adverse Pulmonary effects when compared to the base reference control particles. In summary, two major conclusions can be drawn from these studies: (1) surface treatments can influence the Toxicity of TiO(2) particles in the lung; and (2) the intratracheal instillation-derived, Pulmonary bioassay studies represent an effective preliminary screening tool for inhalation studies with the identical particle-types used in this study.
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comparative Pulmonary Toxicity assessment of single wall carbon nanotubes in rats
Toxicological Sciences, 2003Co-Authors: David B. Warheit, Kenneth L. Reed, B R Laurence, D H Roach, G A M Reynolds, T R WebbAbstract:The aim of this study was to evaluate the acute lung Toxicity of intratracheally instilled single-wall carbon nanotubes (SWCNT) in rats. The lungs of rats were instilled either with 1 or 5 mglkg of the following control or particle types: (1) SWCNT, (2) quartz particles (positive control), (3) carbonyl iron particles (negative control), (4) phosphate-buffered saline (PBS) + 1% Tween 80, or (5) graphite particles (lung tissue studies only). Following exposures, the lungs of PBS and particle-exposed rats were assessed using bronchoalveolar lavage (BAL) fluid biomarkers and cell proliferation methods, and by histopathological evaluation of lung tissue at 24 h, 1 week, 1 month, and 3 months postinstillation. Exposures to high-dose (5 mglkg) SWCNT produced mortality in ∼15% of the SWCNT-instilled rats within 24 h postinstillation. This mortality resulted from mechanical blockage of the upper airways by the instillate and was not due to inherent Pulmonary Toxicity of the instilled SWCNT particulate. Exposures to quartz particles produced significant increases versus controls in Pulmonary inflammation, cytoToxicity, and lung cell parenchymal cell proliferation indices. Exposures to SWCNT produced transient inflammatory and cell injury effects. Results from the lung histopathology component of the study indicated that Pulmonary exposures to quartz particles (5 mglkg) produced dose-dependent inflammatory responses, concomitant with foamy alveolar macrophage accumulation and lung tissue thickening at the sites of normal particle deposition. Pulmonary exposures to carbonyl iron or graphite particles produced no significant adverse effects. Pulmonary exposures to SWCNT in rats produced a non-dose-dependent series of multifocal granulomas, which were evidence of a foreign tissue body reaction and were nonuniform in distribution and not progressive beyond 1 month postexposure (pe). The observation of SWCNT-induced multifocal granulomas is inconsistent with the following: (1) lack of lung Toxicity by assessing lavage parameters, (2) lack of lung Toxicity by measuring cell proliferation parameters, (3) an apparent lack of a dose response relationship, (4) nonuniform distribution of lesions, (5) the paradigm of dust-related lung Toxicity effects, (6) possible regression of effects over time. In addition, the results of two recent exposure assessment studies indicate very low aerosol SWCNT exposures at the workplace. Thus, the physiological relevance of these findings should ultimately be determined by conducting an inhalation Toxicity study.
David B. Warheit - One of the best experts on this subject based on the ideXlab platform.
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comparative Pulmonary Toxicity inhalation and instillation studies with different tio2 particle formulations impact of surface treatments on particle Toxicity
Toxicological Sciences, 2005Co-Authors: David B. Warheit, T R Webb, William J Brock, K P Lee, Kenneth L. ReedAbstract:Most pigment-grade titanium dioxide (TiO(2)) samples that have been tested in Pulmonary Toxicity tests have been of a generic variety-i.e., generally either uncoated particles or TiO(2) particles containing slightly hydrophilic surface treatments/coatings (i.e., base TiO(2)). The objectives of these studies were to assess in rats, the Pulmonary Toxicity of inhaled or intratracheally instilled TiO(2) particle formulations with various surface treatments, ranging from 0-6% alumina (Al(2)O(3)) or alumina and 0-11% amorphous silica (SiO(2)). The Pulmonary effects induced by TiO(2) particles with different surface treatments were compared to reference base TiO(2) particles and controls. In the first study, groups of rats were exposed to high exposure (dose) concentrations of TiO(2) particle formulations for 4 weeks at aerosol concentrations ranging from 1130-1300 mg/m(3) and lung tissues were evaluated by histopathology immediately after exposure, as well as at 2 weeks and 3, 6, and 12 months postexposure. In the second study, groups of rats were intratracheally instilled with nearly identical TiO(2) particle formulations (when compared to the inhalation study) at doses of 2 and 10 mg/kg. Subsequently, the lungs of saline-instilled and TiO(2)-exposed rats were assessed using both bronchoalveolar (BAL) biomarkers and by histopathology/cell proliferation assessment of lung tissues at 24 h, 1 week, 1 and 3 months postexposure. The results from these studies demonstrated that for both inhalation and instillation, only the TiO(2) particle formulations with the largest components of both alumina and amorphous silica surface treatments produced mildly adverse Pulmonary effects when compared to the base reference control particles. In summary, two major conclusions can be drawn from these studies: (1) surface treatments can influence the Toxicity of TiO(2) particles in the lung; and (2) the intratracheal instillation-derived, Pulmonary bioassay studies represent an effective preliminary screening tool for inhalation studies with the identical particle-types used in this study.
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comparative Pulmonary Toxicity assessment of single wall carbon nanotubes in rats
Toxicological Sciences, 2003Co-Authors: David B. Warheit, Kenneth L. Reed, B R Laurence, D H Roach, G A M Reynolds, T R WebbAbstract:The aim of this study was to evaluate the acute lung Toxicity of intratracheally instilled single-wall carbon nanotubes (SWCNT) in rats. The lungs of rats were instilled either with 1 or 5 mglkg of the following control or particle types: (1) SWCNT, (2) quartz particles (positive control), (3) carbonyl iron particles (negative control), (4) phosphate-buffered saline (PBS) + 1% Tween 80, or (5) graphite particles (lung tissue studies only). Following exposures, the lungs of PBS and particle-exposed rats were assessed using bronchoalveolar lavage (BAL) fluid biomarkers and cell proliferation methods, and by histopathological evaluation of lung tissue at 24 h, 1 week, 1 month, and 3 months postinstillation. Exposures to high-dose (5 mglkg) SWCNT produced mortality in ∼15% of the SWCNT-instilled rats within 24 h postinstillation. This mortality resulted from mechanical blockage of the upper airways by the instillate and was not due to inherent Pulmonary Toxicity of the instilled SWCNT particulate. Exposures to quartz particles produced significant increases versus controls in Pulmonary inflammation, cytoToxicity, and lung cell parenchymal cell proliferation indices. Exposures to SWCNT produced transient inflammatory and cell injury effects. Results from the lung histopathology component of the study indicated that Pulmonary exposures to quartz particles (5 mglkg) produced dose-dependent inflammatory responses, concomitant with foamy alveolar macrophage accumulation and lung tissue thickening at the sites of normal particle deposition. Pulmonary exposures to carbonyl iron or graphite particles produced no significant adverse effects. Pulmonary exposures to SWCNT in rats produced a non-dose-dependent series of multifocal granulomas, which were evidence of a foreign tissue body reaction and were nonuniform in distribution and not progressive beyond 1 month postexposure (pe). The observation of SWCNT-induced multifocal granulomas is inconsistent with the following: (1) lack of lung Toxicity by assessing lavage parameters, (2) lack of lung Toxicity by measuring cell proliferation parameters, (3) an apparent lack of a dose response relationship, (4) nonuniform distribution of lesions, (5) the paradigm of dust-related lung Toxicity effects, (6) possible regression of effects over time. In addition, the results of two recent exposure assessment studies indicate very low aerosol SWCNT exposures at the workplace. Thus, the physiological relevance of these findings should ultimately be determined by conducting an inhalation Toxicity study.
