8 research outputs found
Pulmonary toxicity and lung tumorigenic potential of surrogate metal oxides in gas metal arc welding–stainless steel fume: Iron as a primary mediator versus chromium and nickel
In 2017, the International Agency for Research on Cancer classified welding fumes as “car- cinogenic to humans” (Group 1). Both mild steel (MS) welding, where fumes lack carcino- genic chromium and nickel, and stainless steel (SS) increase lung cancer risk in welders; therefore, further research to better understand the toxicity of the individual metals is needed. The objectives were to (1) compare the pulmonary toxicity of chromium (as Cr(III) oxide [Cr2O3] and Cr (VI) calcium chromate [CaCrO4]), nickel [II] oxide (NiO), iron [III] oxide (Fe2O3), and gas metal arc welding-SS (GMAW-SS) fume; and (2) determine if these metal oxides can promote lung tumors. Lung tumor susceptible A/J mice (male, 4–5 weeks old) were exposed by oropharyngeal aspiration to vehicle, GMAW-SS fume (1.7 mg), or a low or high dose of surrogate metal oxides based on the respective weight percent of each metal in the fume: Cr2O3 + CaCrO4 (366 + 5 μg and 731 + 11 μg), NiO (141 and 281 μg), or Fe2O3 (1 and 2 mg). Bronchoalveolar lavage, histopathology, and lung/liver qPCR were done at 1, 7, 28, and 84 days post-aspiration. In a two-stage lung carcinogenesis model, mice were initi- ated with 3-methylcholanthrene (10 μg/g; intraperitoneal; 1x) or corn oil then exposed to metal oxides or vehicle (1 x/week for 5 weeks) by oropharyngeal aspiration. Lung tumors were counted at 30 weeks post-initiation. Results indicate the inflammatory potential of the metal oxides was Fe2O3 \u3e Cr2O3 + CaCrO4 \u3e NiO. Overall, the pneumotoxic effects were negligible for NiO, acute but not persistent for Cr2O3 + CaCrO4, and persistent for the Fe2O3 exposures. Fe2O3, but not Cr2O3 + CaCrO4 or NiO significantly promoted lung tumors. These results provide experimental evidence that Fe2O3 is an important mediator of welding fume toxicity and support epidemiological findings and the IARC classification
Multiwalled carbon nanotube-induced pulmonary inflammatory and fibrotic responses and genomic changes following aspiration exposure in mice: A 1-year postexposure study
<p>Pulmonary exposure to multiwalled carbon nanotubes (MWCNT) induces an inflammatory and rapid fibrotic response, although the long-term signaling mechanisms are unknown. The aim of this study was to examine the effects of 1, 10, 40, or 80 μg MWCNT administered by pharyngeal aspiration on bronchoalveolar lavage (BAL) fluid for polymorphonuclear cell (PMN) infiltration, lactate dehydrogenase (LDH) activity, and lung histopathology for inflammatory and fibrotic responses in mouse lungs 1 mo, 6 mo, and 1 yr postexposure. Further, a 120-μg crocidolite asbestos group was incorporated as a positive control for comparative purposes. Results showed that MWCNT increased BAL fluid LDH activity and PMN infiltration in a dose-dependent manner at all three postexposure times. Asbestos exposure elevated LDH activity at all 3 postexposure times and PMN infiltration at 1 mo and 6 mo postexposure. Pathological changes in the lung, the presence of MWCNT or asbestos, and fibrosis were noted at 40 and 80 μg MWCNT and in asbestos-exposed mice at 1 yr postexposure. To determine potential signaling pathways involved with MWCNT-associated pathological changes in comparison to asbestos, up- and down-regulated gene expression was determined in lung tissue at 1 yr postexposure. Exposure to MWCNT tended to favor those pathways involved in immune responses, specifically T-cell responses, whereas exposure to asbestos tended to favor pathways involved in oxygen species production, electron transport, and cancer. Data indicate that MWCNT are biopersistent in the lung and induce inflammatory and fibrotic pathological alterations similar to those of crocidolite asbestos, but may reach these endpoints by different mechanisms.</p
Supplemental Material, DS2_IJT_10.11771091581818779038 - Similar and Differential Canonical Pathways and Biological Processes Associated With Multiwalled Carbon Nanotube and Asbestos-Induced Pulmonary Fibrosis: A 1-Year Postexposure Study
<p>Supplemental Material, DS2_IJT_10.11771091581818779038 for Similar and Differential Canonical Pathways and Biological Processes Associated With Multiwalled Carbon Nanotube and Asbestos-Induced Pulmonary Fibrosis: A 1-Year Postexposure Study by Julian M. Dymacek, Brandi N. Snyder-Talkington, Rebecca Raese, Chunlin Dong, Salvi Singh, Dale W. Porter, Barbara Ducatman, Michael G. Wolfarth, Michal E. Andrew, Lori Battelli, Vincent Castranova, Yong Qian, and Nancy L. Guo in International Journal of Toxicology</p
Supplemental Material, DS1_IJT_10.11771091581818779038 - Similar and Differential Canonical Pathways and Biological Processes Associated With Multiwalled Carbon Nanotube and Asbestos-Induced Pulmonary Fibrosis: A 1-Year Postexposure Study
<p>Supplemental Material, DS1_IJT_10.11771091581818779038 for Similar and Differential Canonical Pathways and Biological Processes Associated With Multiwalled Carbon Nanotube and Asbestos-Induced Pulmonary Fibrosis: A 1-Year Postexposure Study by Julian M. Dymacek, Brandi N. Snyder-Talkington, Rebecca Raese, Chunlin Dong, Salvi Singh, Dale W. Porter, Barbara Ducatman, Michael G. Wolfarth, Michal E. Andrew, Lori Battelli, Vincent Castranova, Yong Qian, and Nancy L. Guo in International Journal of Toxicology</p
Short-Term Pulmonary Toxicity Assessment of Pre- and Post-incinerated Organomodified Nanoclay in Mice
Organomodified nanoclays
(ONCs) are increasingly used as filler
materials to improve nanocomposite strength, wettability, flammability,
and durability. However, pulmonary risks associated with exposure
along their chemical lifecycle are unknown. This study’s objective
was to compare pre- and post-incinerated forms of uncoated and organomodified
nanoclays for potential pulmonary inflammation, toxicity, and systemic
blood response. Mice were exposed <i>via</i> aspiration
to low (30 μg) and high (300 μg) doses of preincinerated
uncoated montmorillonite nanoclay (CloisNa), ONC (Clois30B), their
respective incinerated forms (I-CloisNa and I-Clois30B), and crystalline
silica (CS). Lung and blood tissues were collected at days 1, 7, and
28 to compare toxicity and inflammation indices. Well-dispersed CloisNa
caused a robust inflammatory response characterized by neutrophils,
macrophages, and particle-laden granulomas. Alternatively, Clois30B,
I-Clois30B, and CS high-dose exposures elicited a low grade, persistent
inflammatory response. High-dose Clois30B exposure exhibited moderate
increases in lung damage markers and a delayed macrophage recruitment
cytokine signature peaking at day 7 followed by a fibrotic tissue
signature at day 28, similar to CloisNa. I-CloisNa exhibited acute,
transient inflammation with quick recovery. Conversely, high-dose
I-Clois30B caused a weak initial inflammatory signal but showed comparable
pro-inflammatory signaling to CS at day 28. The data demonstrate that
ONC pulmonary toxicity and inflammatory potential relies on coating
presence and incineration status in that coated and incinerated nanoclay
exhibited less inflammation and granuloma formation than pristine
montmorillonite. High doses of both pre- and post-incinerated ONC,
with different surface morphologies, may harbor potential pulmonary
health hazards over long-term occupational exposures
Short-Term Pulmonary Toxicity Assessment of Pre- and Post-incinerated Organomodified Nanoclay in Mice
Organomodified nanoclays
(ONCs) are increasingly used as filler
materials to improve nanocomposite strength, wettability, flammability,
and durability. However, pulmonary risks associated with exposure
along their chemical lifecycle are unknown. This study’s objective
was to compare pre- and post-incinerated forms of uncoated and organomodified
nanoclays for potential pulmonary inflammation, toxicity, and systemic
blood response. Mice were exposed <i>via</i> aspiration
to low (30 μg) and high (300 μg) doses of preincinerated
uncoated montmorillonite nanoclay (CloisNa), ONC (Clois30B), their
respective incinerated forms (I-CloisNa and I-Clois30B), and crystalline
silica (CS). Lung and blood tissues were collected at days 1, 7, and
28 to compare toxicity and inflammation indices. Well-dispersed CloisNa
caused a robust inflammatory response characterized by neutrophils,
macrophages, and particle-laden granulomas. Alternatively, Clois30B,
I-Clois30B, and CS high-dose exposures elicited a low grade, persistent
inflammatory response. High-dose Clois30B exposure exhibited moderate
increases in lung damage markers and a delayed macrophage recruitment
cytokine signature peaking at day 7 followed by a fibrotic tissue
signature at day 28, similar to CloisNa. I-CloisNa exhibited acute,
transient inflammation with quick recovery. Conversely, high-dose
I-Clois30B caused a weak initial inflammatory signal but showed comparable
pro-inflammatory signaling to CS at day 28. The data demonstrate that
ONC pulmonary toxicity and inflammatory potential relies on coating
presence and incineration status in that coated and incinerated nanoclay
exhibited less inflammation and granuloma formation than pristine
montmorillonite. High doses of both pre- and post-incinerated ONC,
with different surface morphologies, may harbor potential pulmonary
health hazards over long-term occupational exposures
<i>In Vivo</i> Toxicity Assessment of Occupational Components of the Carbon Nanotube Life Cycle To Provide Context to Potential Health Effects
Pulmonary
toxicity studies on carbon nanotubes focus primarily
on as-produced materials and rarely are guided by a life cycle perspective
or integration with exposure assessment. Understanding toxicity beyond
the as-produced, or pure native material, is critical, due to modifications
needed to overcome barriers to commercialization of applications.
In the first series of studies, the toxicity of as-produced carbon
nanotubes and their polymer-coated counterparts was evaluated in reference
to exposure assessment, material characterization, and stability of
the polymer coating in biological fluids. The second series of studies
examined the toxicity of aerosols generated from sanding polymer-coated
carbon-nanotube-embedded or neat composites. Postproduction modification
by polymer coating did not enhance pulmonary injury, inflammation,
and pathology or <i>in vitro</i> genotoxicity of as-produced
carbon nanotubes, and for a particular coating, toxicity was significantly
attenuated. The aerosols generated from sanding composites embedded
with polymer-coated carbon nanotubes contained no evidence of free
nanotubes. The percent weight incorporation of polymer-coated carbon
nanotubes, 0.15% or 3% by mass, and composite matrix utilized altered
the particle size distribution and, in certain circumstances, influenced
acute <i>in vivo</i> toxicity. Our study provides perspective
that, while the number of workers and consumers increases along the
life cycle, toxicity and/or potential for exposure to the as-produced
material may greatly diminish
<i>In Vivo</i> Toxicity Assessment of Occupational Components of the Carbon Nanotube Life Cycle To Provide Context to Potential Health Effects
Pulmonary
toxicity studies on carbon nanotubes focus primarily
on as-produced materials and rarely are guided by a life cycle perspective
or integration with exposure assessment. Understanding toxicity beyond
the as-produced, or pure native material, is critical, due to modifications
needed to overcome barriers to commercialization of applications.
In the first series of studies, the toxicity of as-produced carbon
nanotubes and their polymer-coated counterparts was evaluated in reference
to exposure assessment, material characterization, and stability of
the polymer coating in biological fluids. The second series of studies
examined the toxicity of aerosols generated from sanding polymer-coated
carbon-nanotube-embedded or neat composites. Postproduction modification
by polymer coating did not enhance pulmonary injury, inflammation,
and pathology or <i>in vitro</i> genotoxicity of as-produced
carbon nanotubes, and for a particular coating, toxicity was significantly
attenuated. The aerosols generated from sanding composites embedded
with polymer-coated carbon nanotubes contained no evidence of free
nanotubes. The percent weight incorporation of polymer-coated carbon
nanotubes, 0.15% or 3% by mass, and composite matrix utilized altered
the particle size distribution and, in certain circumstances, influenced
acute <i>in vivo</i> toxicity. Our study provides perspective
that, while the number of workers and consumers increases along the
life cycle, toxicity and/or potential for exposure to the as-produced
material may greatly diminish