Pulmonary Toxicology

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Kenneth L Reed - One of the best experts on this subject based on the ideXlab platform.

  • Pulmonary bioassay studies with nanoscale and fine quartz particles in rats toxicity is not dependent upon particle size but on surface characteristics
    Toxicological Sciences, 2007
    Co-Authors: David B Warheit, T R Webb, Vicki L Colvin, Kenneth L Reed, Christie M Sayes
    Abstract:

    Pulmonary Toxicology studies in rats demonstrate that nanoparticles are more toxic than fine-sized particles of similar chemistry. This study, however, provides evidence to contradict this theory. The aims of the study were (1) to compare the toxicity of synthetic 50 nm nanoquartz I particles versus (mined) Min-USil quartz (~500 nm); the toxicity of synthetic 12 nm nanoquartz II particles versus (mined) Min-U-Sil (~500 nm) versus (synthetic) fine-quartz particles (300 nm); and (2) to evaluate the surface activities among the samples as they relate to toxicity. Wellcharacterized samples were tested for surface activity and hemolytic potential. In addition, groups of rats were instilled with either doses of 1 or 5 mg/kg of carbonyl iron (CI) or various aquartz particle types in phosphate-buffered saline solution and subsequently assessed using bronchoalveolar lavage fluid biomarkers, cell proliferation, and histopathological evaluation of lung tissue at 24 h, 1 week, 1 month, and 3 months postexposure. Exposures to the various a-quartz particles produced differential degrees of Pulmonary inflammation and cytotoxicity, which were not always consistent with particle size but correlated with surface activity, particularly hemolytic potential. Lung tissue evaluations of three of the quartz samples demonstrated ‘‘typical’’ quartzrelated effects—dose-dependent lung inflammatory macrophage accumulation responses concomitant with early development of Pulmonary fibrosis. The various a-quartz‐related effects were similar qualitatively but with different potencies. The range of particle-related toxicities and histopathological effects in descending order were nanoscale quartz II ¼ Min-U-Sil quartz > fine quartz > nanoscale quartz I > CI particles. The results demon

  • Pulmonary instillation studies with nanoscale tio2 rods and dots in rats toxicity is not dependent upon particle size and surface area
    Toxicological Sciences, 2006
    Co-Authors: David B Warheit, T R Webb, Vicki L Colvin, Christie M Sayes, Kenneth L Reed
    Abstract:

    Pulmonary Toxicology studies in rats demonstrate that nanoparticles administered to the lung are more toxic than larger, fine-sized particles of similar chemistry at identical mass concentrations. The aim of this study was to evaluate the acute lung toxicity in rats of intratracheally instilled pigment-grade TiO2 particles (rutile-type particle size = approximately 300 nm) versus nanoscale TiO2 rods (anatase = 200 nm x 35 nm) or nanoscale TiO2 dots (anatase = approximately 10 nm) compared with a positive control particle type, quartz. Groups of rats were instilled with doses of 1 or 5 mg/kg of the various particle types in phosphate-buffered saline (PBS). Subsequently, the lungs of PBS- and particle-exposed rats were assessed using bronchoalveolar lavage fluid biomarkers, cell proliferation methods, and by the histopathological evaluation of lung tissue at 24 h, 1 week, 1 month, and 3 months postinstillation exposure. Exposures to nanoscale TiO2 rods or nanoscale TiO2 dots produced transient inflammatory and cell injury effects at 24 h postexposure (pe) and were not different from the Pulmonary effects of larger sized TiO2 particle exposures. In contrast, Pulmonary exposures to quartz particles in rats produced a dose-dependent lung inflammatory response characterized by neutrophils and foamy lipid-containing alveolar macrophage accumulation as well as evidence of early lung tissue thickening consistent with the development of Pulmonary fibrosis. The results described herein provide the first example of nanoscale particle types which are not more cytotoxic or inflammogenic to the lung compared to larger sized particles of similar composition. Furthermore, these findings run counter to the postulation that surface area is a major factor associated with the Pulmonary toxicity of nanoscale particle types.

Christie M Sayes - One of the best experts on this subject based on the ideXlab platform.

  • Pulmonary bioassay studies with nanoscale and fine quartz particles in rats toxicity is not dependent upon particle size but on surface characteristics
    Toxicological Sciences, 2007
    Co-Authors: David B Warheit, T R Webb, Vicki L Colvin, Kenneth L Reed, Christie M Sayes
    Abstract:

    Pulmonary Toxicology studies in rats demonstrate that nanoparticles are more toxic than fine-sized particles of similar chemistry. This study, however, provides evidence to contradict this theory. The aims of the study were (1) to compare the toxicity of synthetic 50 nm nanoquartz I particles versus (mined) Min-USil quartz (~500 nm); the toxicity of synthetic 12 nm nanoquartz II particles versus (mined) Min-U-Sil (~500 nm) versus (synthetic) fine-quartz particles (300 nm); and (2) to evaluate the surface activities among the samples as they relate to toxicity. Wellcharacterized samples were tested for surface activity and hemolytic potential. In addition, groups of rats were instilled with either doses of 1 or 5 mg/kg of carbonyl iron (CI) or various aquartz particle types in phosphate-buffered saline solution and subsequently assessed using bronchoalveolar lavage fluid biomarkers, cell proliferation, and histopathological evaluation of lung tissue at 24 h, 1 week, 1 month, and 3 months postexposure. Exposures to the various a-quartz particles produced differential degrees of Pulmonary inflammation and cytotoxicity, which were not always consistent with particle size but correlated with surface activity, particularly hemolytic potential. Lung tissue evaluations of three of the quartz samples demonstrated ‘‘typical’’ quartzrelated effects—dose-dependent lung inflammatory macrophage accumulation responses concomitant with early development of Pulmonary fibrosis. The various a-quartz‐related effects were similar qualitatively but with different potencies. The range of particle-related toxicities and histopathological effects in descending order were nanoscale quartz II ¼ Min-U-Sil quartz > fine quartz > nanoscale quartz I > CI particles. The results demon

  • Pulmonary instillation studies with nanoscale tio2 rods and dots in rats toxicity is not dependent upon particle size and surface area
    Toxicological Sciences, 2006
    Co-Authors: David B Warheit, T R Webb, Vicki L Colvin, Christie M Sayes, Kenneth L Reed
    Abstract:

    Pulmonary Toxicology studies in rats demonstrate that nanoparticles administered to the lung are more toxic than larger, fine-sized particles of similar chemistry at identical mass concentrations. The aim of this study was to evaluate the acute lung toxicity in rats of intratracheally instilled pigment-grade TiO2 particles (rutile-type particle size = approximately 300 nm) versus nanoscale TiO2 rods (anatase = 200 nm x 35 nm) or nanoscale TiO2 dots (anatase = approximately 10 nm) compared with a positive control particle type, quartz. Groups of rats were instilled with doses of 1 or 5 mg/kg of the various particle types in phosphate-buffered saline (PBS). Subsequently, the lungs of PBS- and particle-exposed rats were assessed using bronchoalveolar lavage fluid biomarkers, cell proliferation methods, and by the histopathological evaluation of lung tissue at 24 h, 1 week, 1 month, and 3 months postinstillation exposure. Exposures to nanoscale TiO2 rods or nanoscale TiO2 dots produced transient inflammatory and cell injury effects at 24 h postexposure (pe) and were not different from the Pulmonary effects of larger sized TiO2 particle exposures. In contrast, Pulmonary exposures to quartz particles in rats produced a dose-dependent lung inflammatory response characterized by neutrophils and foamy lipid-containing alveolar macrophage accumulation as well as evidence of early lung tissue thickening consistent with the development of Pulmonary fibrosis. The results described herein provide the first example of nanoscale particle types which are not more cytotoxic or inflammogenic to the lung compared to larger sized particles of similar composition. Furthermore, these findings run counter to the postulation that surface area is a major factor associated with the Pulmonary toxicity of nanoscale particle types.

David B Warheit - One of the best experts on this subject based on the ideXlab platform.

  • hazard and risk assessment strategies for nanoparticle exposures how far have we come in the past 10 years
    F1000Research, 2018
    Co-Authors: David B Warheit
    Abstract:

    Nanotechnology is an emerging, cross-disciplinary technology designed to create and synthesize new materials at the nanoscale (generally defined as a particle size range of ≤10 -9 meters) to generate innovative or altered material properties. The particle properties can be modified to promote different and more flexible applications, resulting in consumer benefits, particularly in medical, cosmetic, and industrial applications. As this applied science matures and flourishes, concerns have arisen regarding potential health effects of exposures to untested materials, as many newly developed products have not been adequately evaluated. Indeed, it is necessary to ensure that societal and commercial advantages are not outweighed by potential human health or environmental disadvantages. Therefore, a variety of international planning activities or research efforts have been proposed or implemented, particularly in the European Union and United States, with the expectation that significant advances will be made in understanding potential hazards related to exposures in the occupational and/or consumer environments. One of the first conclusions reached regarding hazardous effects of nanoparticles stemmed from the findings of early Pulmonary Toxicology studies, suggesting that lung exposures to ultrafine particles were more toxic than those to larger, fine-sized particles of similar chemistry. This review documents some of the conceptual planning efforts, implementation strategies/activities, and research accomplishments over the past 10 years or so. It also highlights (in this author’s opinion) some shortcomings in the research efforts and accomplishments over the same duration. In general, much progress has been made in developing and implementing environmental, health, and safety research-based protocols for addressing nanosafety issues. However, challenges remain in adequately investigating health effects given 1) many different nanomaterial types, 2) various potential routes of exposure, 3) nanomaterial characterization issues, 4) limitations in research methodologies, such as time-course and dose-response issues, and 5) inadequate in vitro methodologies for in vivo standardized, guideline toxicity testing.

  • Pulmonary bioassay studies with nanoscale and fine quartz particles in rats toxicity is not dependent upon particle size but on surface characteristics
    Toxicological Sciences, 2007
    Co-Authors: David B Warheit, T R Webb, Vicki L Colvin, Kenneth L Reed, Christie M Sayes
    Abstract:

    Pulmonary Toxicology studies in rats demonstrate that nanoparticles are more toxic than fine-sized particles of similar chemistry. This study, however, provides evidence to contradict this theory. The aims of the study were (1) to compare the toxicity of synthetic 50 nm nanoquartz I particles versus (mined) Min-USil quartz (~500 nm); the toxicity of synthetic 12 nm nanoquartz II particles versus (mined) Min-U-Sil (~500 nm) versus (synthetic) fine-quartz particles (300 nm); and (2) to evaluate the surface activities among the samples as they relate to toxicity. Wellcharacterized samples were tested for surface activity and hemolytic potential. In addition, groups of rats were instilled with either doses of 1 or 5 mg/kg of carbonyl iron (CI) or various aquartz particle types in phosphate-buffered saline solution and subsequently assessed using bronchoalveolar lavage fluid biomarkers, cell proliferation, and histopathological evaluation of lung tissue at 24 h, 1 week, 1 month, and 3 months postexposure. Exposures to the various a-quartz particles produced differential degrees of Pulmonary inflammation and cytotoxicity, which were not always consistent with particle size but correlated with surface activity, particularly hemolytic potential. Lung tissue evaluations of three of the quartz samples demonstrated ‘‘typical’’ quartzrelated effects—dose-dependent lung inflammatory macrophage accumulation responses concomitant with early development of Pulmonary fibrosis. The various a-quartz‐related effects were similar qualitatively but with different potencies. The range of particle-related toxicities and histopathological effects in descending order were nanoscale quartz II ¼ Min-U-Sil quartz > fine quartz > nanoscale quartz I > CI particles. The results demon

  • Pulmonary instillation studies with nanoscale tio2 rods and dots in rats toxicity is not dependent upon particle size and surface area
    Toxicological Sciences, 2006
    Co-Authors: David B Warheit, T R Webb, Vicki L Colvin, Christie M Sayes, Kenneth L Reed
    Abstract:

    Pulmonary Toxicology studies in rats demonstrate that nanoparticles administered to the lung are more toxic than larger, fine-sized particles of similar chemistry at identical mass concentrations. The aim of this study was to evaluate the acute lung toxicity in rats of intratracheally instilled pigment-grade TiO2 particles (rutile-type particle size = approximately 300 nm) versus nanoscale TiO2 rods (anatase = 200 nm x 35 nm) or nanoscale TiO2 dots (anatase = approximately 10 nm) compared with a positive control particle type, quartz. Groups of rats were instilled with doses of 1 or 5 mg/kg of the various particle types in phosphate-buffered saline (PBS). Subsequently, the lungs of PBS- and particle-exposed rats were assessed using bronchoalveolar lavage fluid biomarkers, cell proliferation methods, and by the histopathological evaluation of lung tissue at 24 h, 1 week, 1 month, and 3 months postinstillation exposure. Exposures to nanoscale TiO2 rods or nanoscale TiO2 dots produced transient inflammatory and cell injury effects at 24 h postexposure (pe) and were not different from the Pulmonary effects of larger sized TiO2 particle exposures. In contrast, Pulmonary exposures to quartz particles in rats produced a dose-dependent lung inflammatory response characterized by neutrophils and foamy lipid-containing alveolar macrophage accumulation as well as evidence of early lung tissue thickening consistent with the development of Pulmonary fibrosis. The results described herein provide the first example of nanoscale particle types which are not more cytotoxic or inflammogenic to the lung compared to larger sized particles of similar composition. Furthermore, these findings run counter to the postulation that surface area is a major factor associated with the Pulmonary toxicity of nanoscale particle types.

Iacopo Zanardi - One of the best experts on this subject based on the ideXlab platform.

  • The ozone paradox: ozone is a strong oxidant as well as a medical drug.
    Medicinal research reviews, 2009
    Co-Authors: Velio Bocci, Emma Borrelli, Valter Travagli, Iacopo Zanardi
    Abstract:

    After five decades characterized by empiricism and several pitfalls, some of the basic mechanisms of action of ozone in Pulmonary Toxicology and in medicine have been clarified. The present knowledge allows to understand the prolonged inhalation of ozone can be very deleterious first for the lungs and successively for the whole organism. On the other hand, a small ozone dose well calibrated against the potent antioxidant capacity of blood can trigger several useful biochemical mechanisms and reactivate the antioxidant system. In detail, firstly ex vivo and second during the infusion of ozonated blood into the donor, the ozone therapy approach involves blood cells and the endothelium, which by transferring the ozone messengers to billions of cells will generate a therapeutic effect. Thus, in spite of a common prejudice, single ozone doses can be therapeutically used in selected human diseases without any toxicity or side effects. Moreover, the versatility and amplitude of beneficial effect of ozone applications have become evident in orthopedics, cutaneous, and mucosal infections as well as in dentistry.

T R Webb - One of the best experts on this subject based on the ideXlab platform.

  • Pulmonary bioassay studies with nanoscale and fine quartz particles in rats toxicity is not dependent upon particle size but on surface characteristics
    Toxicological Sciences, 2007
    Co-Authors: David B Warheit, T R Webb, Vicki L Colvin, Kenneth L Reed, Christie M Sayes
    Abstract:

    Pulmonary Toxicology studies in rats demonstrate that nanoparticles are more toxic than fine-sized particles of similar chemistry. This study, however, provides evidence to contradict this theory. The aims of the study were (1) to compare the toxicity of synthetic 50 nm nanoquartz I particles versus (mined) Min-USil quartz (~500 nm); the toxicity of synthetic 12 nm nanoquartz II particles versus (mined) Min-U-Sil (~500 nm) versus (synthetic) fine-quartz particles (300 nm); and (2) to evaluate the surface activities among the samples as they relate to toxicity. Wellcharacterized samples were tested for surface activity and hemolytic potential. In addition, groups of rats were instilled with either doses of 1 or 5 mg/kg of carbonyl iron (CI) or various aquartz particle types in phosphate-buffered saline solution and subsequently assessed using bronchoalveolar lavage fluid biomarkers, cell proliferation, and histopathological evaluation of lung tissue at 24 h, 1 week, 1 month, and 3 months postexposure. Exposures to the various a-quartz particles produced differential degrees of Pulmonary inflammation and cytotoxicity, which were not always consistent with particle size but correlated with surface activity, particularly hemolytic potential. Lung tissue evaluations of three of the quartz samples demonstrated ‘‘typical’’ quartzrelated effects—dose-dependent lung inflammatory macrophage accumulation responses concomitant with early development of Pulmonary fibrosis. The various a-quartz‐related effects were similar qualitatively but with different potencies. The range of particle-related toxicities and histopathological effects in descending order were nanoscale quartz II ¼ Min-U-Sil quartz > fine quartz > nanoscale quartz I > CI particles. The results demon

  • Pulmonary instillation studies with nanoscale tio2 rods and dots in rats toxicity is not dependent upon particle size and surface area
    Toxicological Sciences, 2006
    Co-Authors: David B Warheit, T R Webb, Vicki L Colvin, Christie M Sayes, Kenneth L Reed
    Abstract:

    Pulmonary Toxicology studies in rats demonstrate that nanoparticles administered to the lung are more toxic than larger, fine-sized particles of similar chemistry at identical mass concentrations. The aim of this study was to evaluate the acute lung toxicity in rats of intratracheally instilled pigment-grade TiO2 particles (rutile-type particle size = approximately 300 nm) versus nanoscale TiO2 rods (anatase = 200 nm x 35 nm) or nanoscale TiO2 dots (anatase = approximately 10 nm) compared with a positive control particle type, quartz. Groups of rats were instilled with doses of 1 or 5 mg/kg of the various particle types in phosphate-buffered saline (PBS). Subsequently, the lungs of PBS- and particle-exposed rats were assessed using bronchoalveolar lavage fluid biomarkers, cell proliferation methods, and by the histopathological evaluation of lung tissue at 24 h, 1 week, 1 month, and 3 months postinstillation exposure. Exposures to nanoscale TiO2 rods or nanoscale TiO2 dots produced transient inflammatory and cell injury effects at 24 h postexposure (pe) and were not different from the Pulmonary effects of larger sized TiO2 particle exposures. In contrast, Pulmonary exposures to quartz particles in rats produced a dose-dependent lung inflammatory response characterized by neutrophils and foamy lipid-containing alveolar macrophage accumulation as well as evidence of early lung tissue thickening consistent with the development of Pulmonary fibrosis. The results described herein provide the first example of nanoscale particle types which are not more cytotoxic or inflammogenic to the lung compared to larger sized particles of similar composition. Furthermore, these findings run counter to the postulation that surface area is a major factor associated with the Pulmonary toxicity of nanoscale particle types.