Last data update: Dec 09, 2024. (Total: 48320 publications since 2009)
Records 1-12 (of 12 Records) |
Query Trace: Mandler K[original query] |
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Pulmonary evaluation of whole-body inhalation exposure of polycarbonate (PC) filament 3D printer emissions in rats
Farcas MT , McKinney W , Mandler WK , Knepp AK , Battelli L , Friend SA , Stefaniak AB , Service S , Kashon M , LeBouf RF , Thomas TA , Matheson J , Qian Y . J Toxicol Environ Health A 2024 87 (8) 325-341 During fused filament fabrication (FFF) 3D printing with polycarbonate (PC) filament, a release of ultrafine particles (UFPs) and volatile organic compounds (VOCs) occurs. This study aimed to determine PC filament printing emission-induced toxicity in rats via whole-body inhalation exposure. Male Sprague Dawley rats were exposed to a single concentration (0.529 mg/m(3), 40 nm mean diameter) of the 3D PC filament emissions in a time-course via whole body inhalation for 1, 4, 8, 15, and 30 days (4 hr/day, 4 days/week), and sacrificed 24 hr after the last exposure. Following exposures, rats were assessed for pulmonary and systemic responses. To determine pulmonary injury, total protein and lactate dehydrogenase (LDH) activity, surfactant proteins A and D, total as well as lavage fluid differential cells in bronchoalveolar lavage fluid (BALF) were examined, as well as histopathological analysis of lung and nasal passages was performed. To determine systemic injury, hematological differentials, and blood biomarkers of muscle, metabolic, renal, and hepatic functions were also measured. Results showed that inhalation exposure induced no marked pulmonary or systemic toxicity in rats. In conclusion, inhalation exposure of rats to a low concentration of PC filament emissions produced no significant pulmonary or systemic toxicity. |
Inhalation of polycarbonate emissions generated during 3D printing processes affects neuroendocrine function in male rats
Krajnak K , Farcas M , McKinney W , Waugh S , Mandler K , Knepp A , Jackson M , Richardson D , Hammer M , Matheson J , Thomas T , Qian Y . J Toxicol Environ Health A 2023 86 (16) 1-22 Three-dimensional (3D) printing of manufactured goods has increased in the last 10 years. The increased use of this technology has resulted in questions regarding the influence of inhaling emissions generated during printing. The goal of this study was to determine if inhalation of particulate and/or toxic chemicals generated during printing with polycarbonate (PC) plastic affected the neuroendocrine system. Male rats were exposed to 3D-printer emissions (592 µg particulate/m(3) air) or filtered air for 4 h/day (d), 4 days/week and total exposures lengths were 1, 4, 8, 15 or 30 days. The effects of these exposures on hormone concentrations, and markers of function and/or injury in the olfactory bulb, hypothalamus and testes were measured after 1, 8 and 30 days exposure. Thirty days of exposure to 3D printer emissions resulted in reductions in thyroid stimulating hormone, follicle stimulating hormone and prolactin. These changes were accompanied by (1) elevation in markers of cell injury; (2) reductions in active mitochondria in the olfactory bulb, diminished gonadotropin releasing hormone cells and fibers as well as less tyrosine hydroxylase immunolabeled fibers in the arcuate nucleus; and (3) decrease in spermatogonium. Polycarbonate plastics may contain bisphenol A, and the effects of exposure to these 3D printer-generated emissions on neuroendocrine function are similar to those noted following exposure to bisphenol A. |
Hazardous dusts from the fabrication of countertop: a review
Mandler WK , Qi C , Qian Y . Arch Environ Occup Health 2022 78 (2) 1-9 Artificial countertop materials, including solid surface composites (SSC) and engineered stone (ES) may pose significant pulmonary health risks for workers who manipulate them. These materials have rapidly become popular in the multibillion-dollar countertop industry, rivaling that of natural materials such as granite and marble due to their variety of desirable esthetic qualities and reduced costs. Both SSC and ES consist of a mineral substrate bound together in a polymer matrix. For SSC the mineral is about 70% aluminum trihydrate (ATH) while ES contains up to 95% crystalline silica by weight. Both materials emit airborne dusts when being manipulated with power tools during the fabrication process. Several deaths and dozens of cases of silicosis have been identified worldwide in workers who fabricate ES, while a single case of fatal pulmonary fibrosis has been associated with SCC dust exposure. This review examines the current state of knowledge for both SSC and ES regarding the composition, particle emission characteristics, workplace exposure data, particle constituent toxicity, and possible methods for reducing worker exposure. |
Evaluation of pulmonary effects of 3-D printer emissions from acrylonitrile butadiene styrene using an air-liquid interface model of primary normal human-derived bronchial epithelial cells
Farcas MT , McKinney W , Coyle J , Orandle M , Mandler WK , Stefaniak AB , Bowers L , Battelli L , Richardson D , Hammer MA , Friend SA , Service S , Kashon M , Qi C , Hammond DR , Thomas TA , Matheson J , Qian Y . Int J Toxicol 2022 41 (4) 10915818221093605 This study investigated the inhalation toxicity of the emissions from 3-D printing with acrylonitrile butadiene styrene (ABS) filament using an air-liquid interface (ALI) in vitro model. Primary normal human-derived bronchial epithelial cells (NHBEs) were exposed to ABS filament emissions in an ALI for 4 hours. The mean and mode diameters of ABS emitted particles in the medium were 175 ± 24 and 153 ± 15 nm, respectively. The average particle deposition per surface area of the epithelium was 2.29 × 10(7) ± 1.47 × 10(7) particle/cm(2), equivalent to an estimated average particle mass of 0.144 ± 0.042 μg/cm(2). Results showed exposure of NHBEs to ABS emissions did not significantly affect epithelium integrity, ciliation, mucus production, nor induce cytotoxicity. At 24 hours after the exposure, significant increases in the pro-inflammatory markers IL-12p70, IL-13, IL-15, IFN-γ, TNF-α, IL-17A, VEGF, MCP-1, and MIP-1α were noted in the basolateral cell culture medium of ABS-exposed cells compared to non-exposed chamber control cells. Results obtained from this study correspond with those from our previous in vivo studies, indicating that the increase in inflammatory mediators occur without associated membrane damage. The combination of the exposure chamber and the ALI-based model is promising for assessing 3-D printer emission-induced toxicity. |
Pulmonary and systemic toxicity in rats following inhalation exposure of 3-D printer emissions from acrylonitrile butadiene styrene (ABS) filament
Farcas MT , McKinney W , Qi C , Mandler KW , Battelli L , Friend SA , Stefaniak AB , Jackson M , Orandle M , Winn A , Kashon M , LeBouf RF , Russ KA , Hammond DR , Burns D , Ranpara A , Thomas TA , Matheson J , Qian Y . Inhal Toxicol 2020 32 1-16 BACKGROUND: Fused filament fabrication 3-D printing with acrylonitrile butadiene styrene (ABS) filament emits ultrafine particulates (UFPs) and volatile organic compounds (VOCs). However, the toxicological implications of the emissions generated during 3-D printing have not been fully elucidated. AIM AND METHODS: The goal of this study was to investigate the in vivo toxicity of ABS-emissions from a commercial desktop 3-D printer. Male Sprague Dawley rats were exposed to a single concentration of ABS-emissions or air for 4 hours/day, 4 days/week for five exposure durations (1, 4, 8, 15, and 30 days). At 24 hours after the last exposure, rats were assessed for pulmonary injury, inflammation, and oxidative stress as well as systemic toxicity. RESULTS AND DISCUSSION: 3-D printing generated particulate with average particle mass concentration of 240 ± 90 µg/m³, with an average geometric mean particle mobility diameter of 85 nm (geometric standard deviation = 1.6). The number of macrophages increased significantly at day 15. In bronchoalveolar lavage, IFN-γ and IL-10 were significantly higher at days 1 and 4, with IL-10 levels reaching a peak at day 15 in ABS-exposed rats. Neither pulmonary oxidative stress responses nor histopathological changes of the lungs and nasal passages were found among the treatments. There was an increase in platelets and monocytes in the circulation at day 15. Several serum biomarkers of hepatic and kidney functions were significantly higher at day 1. CONCLUSIONS: At the current experimental conditions applied, it was concluded that the emissions from ABS filament caused minimal transient pulmonary and systemic toxicity. |
In vitro toxicity assessment of respirable solid surface composite sawing particles
Mandler WK , Kang S , Farcas M , Qi C , Friend SA , Qian Y . Toxicol Ind Health 2020 36 (4) 748233720921683 Solid surface composites (SSCs) are a class of popular construction materials composed of aluminum trihydrate and acrylic polymers. Previous investigations have demonstrated that sawing SSC releases substantial airborne dusts, with a number-based geometric mean diameter of 1.05 microm. We reported that in mice, aspiration exposure to airborne SSC dusts induced symptoms of pulmonary inflammation at 24-h postexposure: neutrophilic influx, alveolitis, and increased lactate dehydrogenase (LDH) and pro-inflammatory cytokine levels in lavage fluid. The particles appeared to be poorly cleared, with 81% remaining at 14-day postexposure. The objective of this study was to determine the toxicity specifically of respirable particles on a model of human alveolar macrophages (THP-1). The relative toxicities of subfractions (0.07, 0.66, 1.58, 5.0, and 13.42 microm diameter) of the airborne particles were also determined. THP-1 macrophages were exposed for 24 h to respirable particles from sawing SSC (0, 12.5, 25, 50, or 100 microg/ml) or size-specific fractions (100 microg/ml). Exposure to respirable SSC particles induced THP-1 macrophage toxicity in a dose-dependent manner. Viability was decreased by 15% and 19% after exposure to 50 and 100 microg/ml SSC, respectively, which correlated with increased cell culture supernatant LDH activity by 40% and 70% when compared to control. Reactive oxygen species (ROS) production and inflammatory cytokines were increased in a dose-dependent manner. A size-dependent cytotoxic effect was observed in the cells exposed to subfractions of SSC particles. SSC particles of 0.07, 0.66, and 1.58 microm diameter killed 36%, 17%, and 22% of cells, respectively. These results indicate a potential for cytotoxicity of respirable SSC particles and a relationship between particle size and toxicity, with the smallest fractions appearing to exhibit the greatest toxicity. |
Acrylonitrile butadiene styrene (ABS) and polycarbonate (PC) filaments three-dimensional (3-D) printer emissions-induced cell toxicity
Farcas MT , Stefaniak AB , Knepp AK , Bowers L , Mandler WK , Kashon M , Jackson SR , Stueckle TA , Sisler JD , Friend SA , Qi C , Hammond DR , Thomas TA , Matheson J , Castranova V , Qian Y . Toxicol Lett 2019 317 1-12 During extrusion of some polymers, fused filament fabrication (FFF) 3-D printers emit billions of particles per minute and numerous organic compounds. The scope of this study was to evaluate FFF 3-D printer emission-induced toxicity in human small airway epithelial cells (SAEC). Emissions were generated from a commercially available 3-D printer inside a chamber, while operating for 1.5h with acrylonitrile butadiene styrene (ABS) or polycarbonate (PC) filaments, and collected in cell culture medium. Characterization of the culture medium revealed that repeat print runs with an identical filament yield various amounts of particles and organic compounds. Mean particle sizes in cell culture medium were 201+/-18nm and 202+/-8nm for PC and ABS, respectively. At 24h post-exposure, both PC and ABS emissions induced a dose dependent significant cytotoxicity, oxidative stress, apoptosis, necrosis, and production of pro-inflammatory cytokines and chemokines in SAEC. Though the emissions may not completely represent all possible exposure scenarios, this study indicate that the FFF could induce toxicological effects. Further studies are needed to quantify the detected chemicals in the emissions and their corresponding toxicological effects. |
Mouse pulmonary response to dust from sawing Corian(R), a solid-surface composite material
Mandler WK , Qi C , Orandle MS , Sarkisian K , Mercer RR , Stefaniak AB , Knepp AK , Bowers LN , Battelli LA , Shaffer J , Friend SA , Qian Y , Sisler JD . J Toxicol Environ Health A 2019 82 (11) 1-19 Corian(R), a solid-surface composite (SSC), is composed of alumina trihydrate and acrylic polymer. The aim of the present study was to examine the pulmonary toxicity attributed to exposure to SSC sawing dust. Male mice were exposed to either phosphate buffer saline (PBS, control), 62.5, 125, 250, 500, or 1000 microg of SSC dust, or 1000 microg silica (positive control) via oropharyngeal aspiration. Body weights were measured for the duration of the study. Bronchoalveolar lavage fluid (BALF) and tissues were collected for analysis at 1 and 14 days post-exposure. Enhanced-darkfield and histopathologic analysis was performed to assess particle distribution and inflammatory responses. BALF cells and inflammatory cytokines were measured. The geometric mean diameter of SSC sawing dust following suspension in PBS was 1.25 microm. BALF analysis indicated that lactate dehydrogenase (LDH) activity, inflammatory cells, and pro-inflammatory cytokines were significantly elevated in the 500 and 1000 microg SSC exposure groups at days 1 and 14, suggesting that exposure to these concentrations of SSC induced inflammatory responses, in some cases to a greater degree than the silica positive control. Histopathology indicated the presence of acute alveolitis at all doses at day 1, which was largely resolved by day 14. Alveolar particle deposition and granulomatous mass formation were observed in all exposure groups at day 14. The SSC particles were poorly cleared, with 81% remaining at the end of the observation period. These findings demonstrate that SSC sawing dust exposure induces pulmonary inflammation and damage that warrants further investigation. Abbreviations: ANOVA: Analysis of Variance; ATH: Alumina Trihydrate; BALF: Bronchoalveolar Lavage Fluid; Dpg: Geometric Mean Diameter; FE-SEM: Field Emission Scanning Electron Microscopy; IACUC: Institutional Animal Care and Use Committee; IFN-gamma: Interferon Gamma; IL-1 Beta: Interleukin-1 Beta; IL-10: Interleukin-10; IL-12: Interleukin-12; IL-2: Interleukin-2; IL-4: Interleukin-4; IL-5: Interleukin-5; IL-6: Interleukin-6; KC/GRO: Neutrophil-Activating Protein 3; MMAD: Mass Median Aerodynamic Diameter; PBS: Phosphate-Buffered Saline; PEL: Permissible Exposure Limit; PM: Polymorphonuclear Leukocytes; PNOR: Particles Not Otherwise Regulated; SEM/EDX: Scanning Electron Microscope/Energy-Dispersive X-Ray; SSA: Specific Surface Area; SSC: Solid Surface Composite; TNFalpha: Tumor Necrosis Factor-Alpha; VOC: Volatile Organic Compounds; sigmag: Geometric Standard Deviation. |
Toxicological assessment of dust from sanding micronized copper-treated lumber in vivo
Sisler JD , Mandler WK , Shaffer J , Lee T , McKinney WG , Battelli LA , Orandle MS , Thomas TA , Castranova VC , Qi C , Porter DW , Andrew ME , Fedan JS , Mercer RR , Qian Y . J Hazard Mater 2019 373 630-639 Micronized copper azole (MCA) is a lumber treatment improve longevity. In this study, the in vivo response to PM2.5 sanding dust generated from MCA-treated lumber was compared to that of untreated yellow pine (UYP) or soluble copper azole-treated (CA-C) lumber to determine if the MCA was more bioactive than CA-C. Mice were exposed to doses (28, 140, or 280 mug/mouse) of UYP, MCA, or CA-C sanding dust using oropharyngeal aspiration. Bronchoalveolar lavage fluid (BALF) lactate dehydrogenase activity was increased at 1 day post-exposure to 280 mug/mouse of MCA and CA-C compared to UYP. BALF polymorphonuclear cells were increased by MCA and CA-C. There were increases in BALF cytokines in MCA and CA-C-exposed groups at 1 day post-exposure. Lung histopathology indicated inflammation with infiltration of neutrophils and macrophages. Pulmonary responses were more severe in MCA and CA-C-exposed groups at 1 day post-exposure. MCA caused more severe inflammatory responses than CA-C at 1 day post-exposure. These findings suggest that the MCA and CA-C sanding dusts are more bioactive than the UYP sanding dust, and, moreover, the MCA sanding dust is more bioactive in comparison to the CA-C sanding dust. No chronic toxic effects were observed among all observed sanding dusts. |
Microvascular dysfunction following multi-walled carbon nanotube exposure is mediated by thrombospondin-1 receptor CD47
Mandler WK , Nurkiewicz TR , Porter DW , Kelley EE , Olfert IM . Toxicol Sci 2018 165 (1) 90-99 Pulmonary exposure to multi-walled carbon nanotubes (MWCNT) disrupts peripheral microvascular function. Thrombospondin-1 (TSP-1) is highly expressed during lung injury and has been shown to alter microvascular reactivity. It is unclear exactly how TSP-1 exerts effects on vascular function, but we hypothesized that the TSP-1 receptor CD47 may mediate changes in vasodilation.Wildtype (WT) or CD47 knockout (CD47 KO) C57B6/J-background animals were exposed to 50 microg of MWCNT or saline control via pharyngeal aspiration. Twenty-four hours post-exposure, intravital microscopy was performed to assess arteriolar dilation and venular leukocyte adhesion and rolling. To assess tissue redox status, electron paramagnetic resonance and NOx measurements were performed, while inflammatory biomarkers were measured via multiplex assay.Vasodilation was impaired in the WT+MWCNT group compared to control (57+/-9% vs 90+/-2% relaxation), while CD47 KO animals showed no impairment (108+/-8% relaxation). Venular leukocyte adhesion and rolling increased by > 2-fold, while the CD47 KO group showed no change. Application of the antioxidant apocynin rescued normal leukocyte activity in the WT+MWCNT group. Lung and plasma NOx were reduced in the WT+MWCNT group by 47% and 32%, respectively, while the CD47 KO groups were unchanged from control. Some inflammatory cytokines were increased in the CD47+MWCNT group only.In conclusion, TSP-1 is an important ligand mediating MWCNT-induced microvascular dysfunction, and CD47 is a component of this dysregulation. CD47 activation likely disrupts nitric oxide (*NO) signaling and promotes leukocyte-endothelial interactions. Impaired *NO production, signaling, and bioavailability is linked to a variety of cardiovascular diseases in which TSP-1/CD47 may play an important role. |
Thrombospondin-1 mediates multi-walled carbon nanotube induced impairment of arteriolar dilation
Mandler WK , Nurkiewicz TR , Porter DW , Olfert IM . Nanotoxicology 2016 11 (1) 1-31 Pulmonary exposure to multi-walled carbon nanotubes (MWCNT) has been shown to disrupt endothelium-dependent arteriolar dilation in the peripheral microcirculation. The molecular mechanisms behind these arteriolar disruptions have yet to be fully elucidated. The secreted matricellular matrix protein thrombospondin-1 (TSP-1) is capable of moderating arteriolar vasodilation by inhibiting soluble guanylate cyclase activity. We hypothesized that TSP-1 may be a link between nanomaterial exposure and observed peripheral microvascular dysfunction. To test this hypothesis, wild-type C57B6J (WT) and TSP-1 knockout (KO) mice were exposed via lung aspiration to 50 microg MWCNT or a sham dispersion medium control. Following exposure (24hrs), arteriolar characteristics and reactivity were measured in the gluteus maximus muscle using intravital microscopy (IVM) coupled with microiontophoretic delivery of acetylcholine (ACh) or sodium nitroprusside (SNP). In WT mice exposed to MWCNT, skeletal muscle TSP-1 protein increased > 5-fold compared to sham exposed, and exhibited a 39% and 47% decrease in endothelium-dependent and independent vasodilation, respectively. In contrast, TSP-1 protein was not increased following MWCNT exposure in KO mice and exhibited no loss in dilatory capacity. Microvascular leukocyte leukocyte-endothelium interactions were measured by leukocyte adhesion and rolling activity in assessing third order venules. The WT+MWCNT group demonstrated 223% higher leukocyte rolling compared to WT+SHAM controls. TSP-1 KO animals exposed to MWCNT showed no differences from WT+SHAM control. These data provide evidence that TSP-1 is likely a central mediator of the systemic microvascular dysfunction that follows pulmonary MWCNT exposure. |
Implementing rapid HIV testing with or without risk-reduction counseling in drug treatment centers: results of a randomized trial
Metsch LR , Feaster DJ , Gooden L , Matheson T , Mandler RN , Haynes L , Tross S , Kyle T , Gallup D , Kosinski AS , Douaihy A , Schackman BR , Das M , Lindblad R , Erickson S , Korthuis PT , Martino S , Sorensen JL , Szapocznik J , Walensky R , Branson B , Colfax GN . Am J Public Health 2012 102 (6) 1160-7 OBJECTIVES: We examined the effectiveness of risk reduction counseling and the role of on-site HIV testing in drug treatment. METHODS: Between January and May 2009, we randomized 1281 HIV-negative (or status unknown) adults who reported no past-year HIV testing to (1) referral for off-site HIV testing, (2) HIV risk-reduction counseling with on-site rapid HIV testing, or (3) verbal information about testing only with on-site rapid HIV testing. RESULTS: We defined 2 primary self-reported outcomes a priori: receipt of HIV test results and unprotected anal or vaginal intercourse episodes at 6-month follow-up. The combined on-site rapid testing participants received more HIV test results than off-site testing referral participants (P < .001; Mantel-Haenszel risk ratio = 4.52; 97.5% confidence interval [CI] = 3.57, 5.72). At 6 months, there were no significant differences in unprotected intercourse episodes between the combined on-site testing arms and the referral arm (P = .39; incidence rate ratio [IRR] = 1.04; 97.5% CI = 0.95, 1.14) or the 2 on-site testing arms (P = .81; IRR = 1.03; 97.5% CI = 0.84, 1.26). CONCLUSIONS: This study demonstrated on-site rapid HIV testing's value in drug treatment centers and found no additional benefit from HIV sexual risk-reduction counseling. (Am J Public Health. Published online ahead of print April 19, 2012: e1-e8. doi:10.2105/AJPH.2011.300460.) |
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