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1.
Entropy (Basel) ; 24(8)2022 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-36010722

RESUMO

Complex networks are often used to analyze written text and reports by rendering texts in the form of a semantic network, forming a lexicon of words or key terms. Many existing methods to construct lexicons are based on counting word co-occurrences, having the advantage of simplicity and ease of applicability. Here, we use a quantum semantics approach to generalize such methods, allowing us to model the entanglement of terms and words. We show how quantum semantics can be applied to reveal disciplinary differences in the use of key terms by analyzing 12 scholarly texts that represent the different positions of various disciplinary schools (of conceptual change research) on the same topic (conceptual change). In addition, attention is paid to how closely the lexicons corresponding to different positions can be brought into agreement by suitable tuning of the entanglement factors. In comparing the lexicons, we invoke complex network-based analysis based on exponential matrix transformation and use information theoretic relative entropy (Jensen-Shannon divergence) as the operationalization of differences between lexicons. The results suggest that quantum semantics is a viable way to model the disciplinary differences of lexicons and how they can be tuned for a better agreement.

2.
Ann Work Expo Health ; 66(4): 520-536, 2022 04 22.
Artigo em Inglês | MEDLINE | ID: mdl-34365499

RESUMO

STOFFENMANAGER® and the Advanced REACH Tool (ART) are recommended tools by the European Chemical Agency for regulatory chemical safety assessment. The models are widely used and accepted within the scientific community. STOFFENMANAGER® alone has more than 37 000 users globally and more than 310 000 risk assessment have been carried out by 2020. Regardless of their widespread use, this is the first study evaluating the theoretical backgrounds of each model. STOFFENMANAGER® and ART are based on a modified multiplicative model where an exposure base level (mg m-3) is replaced with a dimensionless intrinsic emission score and the exposure modifying factors are replaced with multipliers that are mainly based on subjective categories that are selected by using exposure taxonomy. The intrinsic emission is a unit of concentration to the substance emission potential that represents the concentration generated in a standardized task without local ventilation. Further information or scientific justification for this selection is not provided. The multipliers have mainly discrete values given in natural logarithm steps (…, 0.3, 1, 3, …) that are allocated by expert judgements. The multipliers scientific reasoning or link to physical quantities is not reported. The models calculate a subjective exposure score, which is then translated to an exposure level (mg m-3) by using a calibration factor. The calibration factor is assigned by comparing the measured personal exposure levels with the exposure score that is calculated for the respective exposure scenarios. A mixed effect regression model was used to calculate correlation factors for four exposure group [e.g. dusts, vapors, mists (low-volatiles), and solid object/abrasion] by using ~1000 measurements for STOFFENMANAGER® and 3000 measurements for ART. The measurement data for calibration are collected from different exposure groups. For example, for dusts the calibration data were pooled from exposure measurements sampled from pharmacies, bakeries, construction industry, and so on, which violates the empirical model basic principles. The calibration databases are not publicly available and thus their quality or subjective selections cannot be evaluated. STOFFENMANAGER® and ART can be classified as subjective categorization tools providing qualitative values as their outputs. By definition, STOFFENMANAGER® and ART cannot be classified as mechanistic models or empirical models. This modeling algorithm does not reflect the physical concept originally presented for the STOFFENMANAGER® and ART. A literature review showed that the models have been validated only at the 'operational analysis' level that describes the model usability. This review revealed that the accuracy of STOFFENMANAGER® is in the range of 100 000 and for ART 100. Calibration and validation studies have shown that typical log-transformed predicted exposure concentration and measured exposure levels often exhibit weak Pearson's correlations (r is <0.6) for both STOFFENMANAGER® and ART. Based on these limitations and performance departure from regulatory criteria for risk assessment models, it is recommended that STOFFENMANAGER® and ART regulatory acceptance for chemical safety decision making should be explicitly qualified as to their current deficiencies.


Assuntos
Exposição Ocupacional , Algoritmos , Monitoramento Ambiental , Humanos , Exposição Ocupacional/análise , Medição de Risco , Ventilação
3.
Artigo em Inglês | MEDLINE | ID: mdl-33430311

RESUMO

Pulmonary exposure to micro- and nanoscaled particles has been widely linked to adverse health effects and high concentrations of respirable particles are expected to occur within and around many industrial settings. In this study, a field-measurement campaign was performed at an industrial manufacturer, during the production of paints. Spatial and personal measurements were conducted and results were used to estimate the mass flows in the facility and the airborne particle release to the outdoor environment. Airborne particle number concentration (1 × 103-1.0 × 104 cm-3), respirable mass (0.06-0.6 mg m-3), and PM10 (0.3-6.5 mg m-3) were measured during pouring activities. In overall; emissions from pouring activities were found to be dominated by coarser particles >300 nm. Even though the raw materials were not identified as nanomaterials by the manufacturers, handling of TiO2 and clays resulted in release of nanometric particles to both workplace air and outdoor environment, which was confirmed by TEM analysis of indoor and stack emission samples. During the measurement period, none of the existing exposure limits in force were exceeded. Particle release to the outdoor environment varied from 6 to 20 g ton-1 at concentrations between 0.6 and 9.7 mg m-3 of total suspended dust depending on the powder. The estimated release of TiO2 to outdoors was 0.9 kg per year. Particle release to the environment is not expected to cause any major impact due to atmospheric dilution.


Assuntos
Poluentes Ocupacionais do Ar , Exposição Ocupacional , Poluentes Ocupacionais do Ar/análise , Monitoramento Ambiental , Exposição por Inalação/análise , Exposição Ocupacional/análise , Pintura , Tamanho da Partícula , Titânio
4.
Open Res Eur ; 1: 72, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-37645135

RESUMO

Background: The Registration, Evaluation, Authorization and Restriction of Chemicals (REACH) regulation requires the establishment of Conditions of Use (CoU) for all exposure scenarios to ensure good communication of safe working practices. Setting CoU requires the risk assessment of all relevant Contributing Scenarios (CSs) in the exposure scenario. A new CS has to be created whenever an Operational Condition (OC) is changed, resulting in an excessive number of exposure assessments. An efficient solution is to quantify OC concentrations and to identify reasonable worst-case scenarios with probabilistic exposure modeling. Methods: Here, we appoint CoU for powder pouring during the industrial manufacturing of a paint batch by quantifying OC exposure levels and exposure determinants. The quantification was performed by using stationary measurements and a probabilistic Near-Field/Far-Field (NF/FF) exposure model. Work shift and OC concentration levels were quantified for pouring TiO 2 from big bags and small bags, pouring Micro Mica from small bags, and cleaning. The impact of exposure determinants on NF concentration level was quantified by (1) assessing exposure determinants correlation with the NF exposure level and (2) by performing simulations with different OCs. Results: Emission rate, air mixing between NF and FF and local ventilation were the most relevant exposure determinants affecting NF concentrations. Potentially risky OCs were identified by performing Reasonable Worst Case (RWC) simulations and by comparing the exposure 95 th percentile distribution with 10% of the occupational exposure limit value (OELV). The CS was shown safe except in RWC scenario (ventilation rate from 0.4 to 1.6 1/h, 100 m 3 room, no local ventilation, and NF ventilation of 1.6 m 3/min). Conclusions: The CoU assessment was considered to comply with European Chemicals Agency (ECHA) legislation and EN 689 exposure assessment strategy for testing compliance with OEL values. One RWC scenario would require measurements since the exposure level was 12.5% of the OELV.

5.
Int J Toxicol ; 39(4): 321-327, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32715854

RESUMO

People can be exposed to zinc oxide (ZnO) by inhalation of consumer products or during industrial processes. Zinc oxide nanoparticle (NP) exposure can induce acute inhalation toxicity. The toxicological mechanisms underlying the acute effects on the lungs have long focused on the phagolysosomal dissolution of ZnO NPs in macrophages followed by the release of free Zn2+ ions. However, we postulate an alternative mechanism based on the direct interaction of ZnO NPs with the lung surfactant (LS) layer covering the inside of the alveoli. Therefore, we tested the effect of ZnO NPs and Zn2+ ions on the function of LS in vitro using the constrained drop surfactometer. We found that the ZnO NPs inhibited the LS function, whereas Zn2+ ions did not. To examine the role of lung macrophages in the acute toxicity of inhaled ZnO NPs, mice were treated with Clodrosome, a drug that depletes alveolar macrophages, or Encapsome, the empty carrier of the drug. After macrophage depletion, the mice were exposed to an aerosol of ZnO NPs in whole body plethysmographs recording breathing patterns continuously. Mice in both groups developed shallow breathing (reduced tidal volume) shortly after the onset of exposure to ZnO NPs. This suggests a macrophage-independent mechanism of induction. This study shows that acute inhalation toxicity is caused by ZnO NP interaction with LS, independently of NP dissolution in macrophages.


Assuntos
Pulmão/efeitos dos fármacos , Nanopartículas/toxicidade , Tensão Superficial/efeitos dos fármacos , Óxido de Zinco/toxicidade , Administração por Inalação , Animais , Ácido Clodrônico/administração & dosagem , Feminino , Lipossomos , Pulmão/imunologia , Pulmão/fisiologia , Macrófagos/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Volume de Ventilação Pulmonar/efeitos dos fármacos
6.
J Occup Environ Hyg ; 17(1): 15-29, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31815607

RESUMO

The purpose of the study was to compare measured air and surface concentrations after application of biocidal spray products with concentrations simulated with the ConsExpo Web spray simulation tool. Three different biocidal spray products were applied in a 20 m3 climate test chamber with well-controlled environmental conditions (22 ± 1 °C, 50 ± 2% relative humidity, and air exchange rate of 0.5 h-1). The products included an insect spray in a pressurized spray can, another insect spray product, and a disinfectant, the latter two applied separately with the same pumped spray device. The measurements included released particles, airborne organic compounds in both gas and particle phase, and surface concentrations of organic compounds on the wall and floor in front of the spraying position and on the most remote wall. Spraying time was a few seconds and the air concentrations were measured by sampling on adsorbent tubes at 9-13 times points during 4 hr after spraying. The full chamber experiment was repeated 2-3 times for each product. Due to sedimentation the concentrations of the particles in air decayed faster than explained by the air exchange rate. In spite of that, the non-volatile benzalkonium chlorides in the disinfectant could be measured in the air more than 30 min after spraying. ConsExpo Web simulated concentrations that were about half of the measured concentrations of the active substances when as many as possible of the default simulation parameters were replaced by the experimental values. ConsExpo Web was unable to simulate the observed faster decay of the airborne concentrations of the active substances, which might be due to underestimation of the gravitational particle deposition rates. There was a relatively good agreement between measured surface concentrations on the floor and calculated values based on the dislodgeable amount given in the selected ConsExpo Web scenarios. It is suggested to always supplement simulation tool results with practical measurements when assessing the exposure to a spray product.


Assuntos
Desinfetantes/análise , Exposição Ocupacional/estatística & dados numéricos , Aerossóis/análise , Humanos , Exposição por Inalação/estatística & dados numéricos , Inseticidas/análise , Modelos Estatísticos
7.
Indoor Air ; 29(5): 803-816, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31206776

RESUMO

A particle exposure experiment inside a large climate-controlled chamber was conducted. Data on spatial and temporal distribution of nanoscale and fine aerosols in the range of mobility diameters 8-600 nm were collected with high resolution, for sodium chloride, fluorescein sodium, and silica particles. Exposure scenarios studied included constant and intermittent source emissions, different aggregation conditions, high (10 h-1 ) and low (3.5 h-1 ) air exchange rates (AERs) corresponding to chamber Reynolds number, respectively, equal to 1 × 105 and 3 × 104 . Results are presented and analyzed to highlight the main determinants of exposure and to determine whether the assumptions underlying two-box models hold under various scenarios. The main determinants of exposure found were the source generation rate and the ventilation rate. The effect of particles nature was indiscernible, and the decrease of airborne total number concentrations attributable to surface deposition was estimated lower than 2% when the source was active. A near-field/far-field structure of aerosol concentration was always observed for the AER = 10 h-1 but for AER = 3.5 h-1 , a single-field structure was found. The particle size distribution was always homogeneous in space but a general shift of particle diameter (-8% to +16%) was observed between scenarios in correlation with the AER and with the source position, presumably largely attributable to aggregation.


Assuntos
Aerossóis/análise , Poluentes Atmosféricos/análise , Poluição do Ar em Ambientes Fechados/análise , Monitoramento Ambiental , Humanos , Modelos Teóricos , Nanopartículas , Tamanho da Partícula , Análise Espaço-Temporal , Ventilação
8.
Part Fibre Toxicol ; 16(1): 21, 2019 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-31182122

RESUMO

BACKGROUND: Short-term controlled exposure to diesel exhaust (DE) in chamber studies have shown mixed results on lung and systemic effects. There is a paucity of studies on well-characterized real-life DE exposure in humans. In the present study, 29 healthy volunteers were exposed to DE while sitting as passengers in diesel-powered trains. Exposure in electric trains was used as control scenario. Each train scenario consisted of three consecutive days (6 h/day) ending with biomarker samplings. RESULTS: Combustion-derived air pollutants were considerably higher in the passenger carriages of diesel trains compared with electric trains. The concentrations of black carbon and ultrafine particles were 8.5 µg/m3 and 1.2-1.8 × 105 particles/cm3 higher, respectively, in diesel as compared to electric trains. Net increases of NOx and NO2 concentrations were 317 µg/m3 and 36 µg/m3. Exposure to DE was associated with reduced lung function and increased levels of DNA strand breaks in peripheral blood mononuclear cells (PBMCs), whereas there were unaltered levels of oxidatively damaged DNA, soluble cell adhesion molecules, acute phase proteins in blood and urinary excretion of metabolites of polycyclic aromatic hydrocarbons. Also the microvascular function was unaltered. An increase in the low frequency of heart rate variability measures was observed, whereas time-domain measures were unaltered. CONCLUSION: Exposure to DE inside diesel-powered trains for 3 days was associated with reduced lung function and systemic effects in terms of altered heart rate variability and increased levels of DNA strand breaks in PBMCs compared with electric trains. TRIAL REGISTRATION: ClinicalTrials.Gov ( NCT03104387 ). Registered on March 23rd 2017.


Assuntos
Poluentes Atmosféricos/análise , Sistema Cardiovascular/efeitos dos fármacos , Dano ao DNA , Pulmão/efeitos dos fármacos , Material Particulado/análise , Emissões de Veículos/análise , Poluentes Atmosféricos/toxicidade , Biomarcadores/sangue , Biomarcadores/urina , Sistema Cardiovascular/fisiopatologia , Monitoramento Ambiental , Gasolina , Voluntários Saudáveis , Humanos , Pulmão/fisiopatologia , Material Particulado/toxicidade , Ferrovias , Emissões de Veículos/toxicidade
9.
Part Fibre Toxicol ; 16(1): 23, 2019 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-31182125

RESUMO

BACKGROUND: Little is known about the exposure levels and adverse health effects of occupational exposure to airplane emissions. Diesel exhaust particles are classified as carcinogenic to humans and jet engines produce potentially similar soot particles. Here, we evaluated the potential occupational exposure risk by analyzing particles from a non-commercial airfield and from the apron of a commercial airport. Toxicity of the collected particles was evaluated alongside NIST standard reference diesel exhaust particles (NIST2975) in terms of acute phase response, pulmonary inflammation, and genotoxicity after single intratracheal instillation in mice. RESULTS: Particle exposure levels were up to 1 mg/m3 at the non-commercial airfield. Particulate matter from the non-commercial airfield air consisted of primary and aggregated soot particles, whereas commercial airport sampling resulted in a more heterogeneous mixture of organic compounds including salt, pollen and soot, reflecting the complex occupational exposure at an apron. The particle contents of polycyclic aromatic hydrocarbons and metals were similar to the content in NIST2975. Mice were exposed to doses 6, 18 and 54 µg alongside carbon black (Printex 90) and NIST2975 and euthanized after 1, 28 or 90 days. Dose-dependent increases in total number of cells, neutrophils, and eosinophils in bronchoalveolar lavage fluid were observed on day 1 post-exposure for all particles. Lymphocytes were increased for all four particle types on 28 days post-exposure as well as for neutrophil influx for jet engine particles and carbon black nanoparticles. Increased Saa3 mRNA levels in lung tissue and increased SAA3 protein levels in plasma were observed on day 1 post-exposure. Increased levels of DNA strand breaks in bronchoalveolar lavage cells and liver tissue were observed for both particles, at single dose levels across doses and time points. CONCLUSIONS: Pulmonary exposure of mice to particles collected at two airports induced acute phase response, inflammation, and genotoxicity similar to standard diesel exhaust particles and carbon black nanoparticles, suggesting similar physicochemical properties and toxicity of jet engine particles and diesel exhaust particles. Given this resemblance as well as the dose-response relationship between diesel exhaust exposure and lung cancer, occupational exposure to jet engine emissions at the two airports should be minimized.


Assuntos
Poluentes Ocupacionais do Ar/toxicidade , Aeroportos , Dano ao DNA , Pulmão/efeitos dos fármacos , Material Particulado/toxicidade , Hidrocarbonetos Policíclicos Aromáticos/toxicidade , Poluentes Ocupacionais do Ar/análise , Poluentes Ocupacionais do Ar/farmacocinética , Animais , Biomarcadores/sangue , Líquido da Lavagem Broncoalveolar/citologia , Feminino , Pulmão/metabolismo , Pulmão/ultraestrutura , Camundongos Endogâmicos C57BL , Exposição Ocupacional/efeitos adversos , Exposição Ocupacional/análise , Material Particulado/análise , Material Particulado/farmacocinética , Hidrocarbonetos Policíclicos Aromáticos/análise , Hidrocarbonetos Policíclicos Aromáticos/farmacocinética , Proteína Amiloide A Sérica/análise , Fatores de Tempo , Distribuição Tecidual
10.
Sci Rep ; 9(1): 8093, 2019 05 30.
Artigo em Inglês | MEDLINE | ID: mdl-31147577

RESUMO

Air pollution is one of the major contributors to the global burden of disease, with particulate matter (PM) as one of its central concerns. Thus, there is a great need for exposure and risk assessments associated with PM pollution. However, current standard measurement techniques bring no knowledge of particle composition or shape, which have been identified among the crucial parameters for toxicology of inhaled particles. We present a method for collecting aerosols via impaction directly onto Transmission Electron Microscopy (TEM) grids, and based on the measured impactor collection efficiency and observed impact patterns we establish a reproducible imaging routine for automated Scanning Electron Microscopy (SEM) analysis. The method is validated by comparison to scanning mobility particle sizer (SMPS) measurements, where a good agreement is found between the particle size distributions (PSD), ensuring a representative description of the sampled aerosol. We furthermore determine sampling conditions for achieving optimal particle coverage on the TEM grids, allowing for a statistical analysis. In summary, the presented method can provide not only a representative PSD, but also detailed statistics on individual particle geometries. If coupled with Energy-dispersive X-ray spectroscopy (EDS) analysis elemental compositions can be assessed as well. This makes it possible to categorize particles both according to size and shape e.g. round and fibres, or agglomerates, as well as classify them based on their elemental composition e.g. salt, soot, or metals. Combined this method brings crucial knowledge for improving the foundation for PM risk assessments on workplaces and in ambient conditions with complex aerosol pollution.

11.
Environ Sci Technol ; 53(8): 4579-4587, 2019 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-30917278

RESUMO

Diesel-powered trains are used worldwide for passenger transport. The present study aimed to assess air pollution concentrations in passenger cars from diesel and electric trains. Personal exposure monitoring (6-7 h per day) was carried out for 49 days on diesel and 22 days on electric trains. Diesel trains had higher concentrations of all the assessed air pollution components. Average increases (and fold differences) in passenger cars of diesel trains compared with electric trains were for ultrafine particles 212 000 particles/cm3 (35-fold), black carbon 8.3 µg/m3 (6-fold), NO x 316 µg/m3 (8-fold), NO2 38 µg/m3 (3-fold), PM2.5 34 µg/m3 (2-fold), and benzo( a)pyrene 0.14 ng/m3 (6-fold). From time-series data, the pull and push movement modes, the engine in use, and the distance to the locomotive influenced the concentrations inside the diesel trains. In conclusion, concentrations of all air pollutants were significantly elevated in passenger cars in diesel trains compared to electric trains.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Monitoramento Ambiental , Material Particulado , Emissões de Veículos
12.
Part Fibre Toxicol ; 16(1): 13, 2019 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-30879468

RESUMO

BACKGROUND: Previous findings indicate that in utero exposure to nanoparticles may affect the reproductive system in male offspring. Effects such as decreased sperm counts and testicular structural changes in F1 males have been reported following maternal airway exposure to carbon black during gestation. In addition, a previous study in our laboratory suggested that the effects of in utero exposure of nanoparticles may span further than the first generation, as sperm content per gram of testis was significantly lowered in F2 males. In the present study we assessed male fertility parameters following in utero inhalation exposure to carbon black in four generations of mice. RESULTS: Filter measurements demonstrated that the time-mated females were exposed to a mean total suspended particle mass concentration of 4.79 ± 1.86 or 33.87 ± 14.77 mg/m3 for the low and high exposure, respectively. The control exposure was below the detection limit (LOD 0.08 mg/m3). Exposure did not affect gestation and litter parameters in any generation. No significant changes were observed in body and reproductive organ weights, epididymal sperm parameters, daily sperm production, plasma testosterone or fertility. CONCLUSION: In utero exposure to carbon black nanoparticles, at occupationally relevant exposure levels, via maternal whole body inhalation did not affect male-specific reproductive, fertility and litter parameters in four generations of mice.


Assuntos
Exposição por Inalação/efeitos adversos , Exposição Materna/efeitos adversos , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Reprodução/efeitos dos fármacos , Fuligem/toxicidade , Animais , Epididimo/efeitos dos fármacos , Epididimo/crescimento & desenvolvimento , Feminino , Masculino , Camundongos , Camundongos Endogâmicos , Gravidez , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Contagem de Espermatozoides , Motilidade dos Espermatozoides/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Espermatozoides/patologia , Testículo/efeitos dos fármacos , Testículo/crescimento & desenvolvimento
13.
Part Fibre Toxicol ; 15(1): 36, 2018 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-30201004

RESUMO

BACKGROUND: Engineered nanoparticles are smaller than 100 nm and designed to improve or creating even new physico-chemical properties. Consequently, toxicological properties of materials may change as size reaches the nm size-range. We examined outcomes related to the central nervous system in the offspring following maternal inhalation exposure to nanosized carbon black particles (Printex 90). METHODS: Time-mated mice (NMRI) were exposed by inhalation, for 45 min/day to 0, 4.6 or 37 mg/m3 aerosolized carbon black on gestation days 4-18, i.e. for a total of 15 days. Outcomes included maternal lung inflammation (differential cell count in bronchoalveolar lavage fluid and Saa3 mRNA expression in lung tissue), offspring neurohistopathology and behaviour in the open field test. RESULTS: Carbon black exposure did not cause lung inflammation in the exposed females, measured 11 or 28-29 days post-exposure. Glial fibrillary acidic protein (GFAP) expression levels were dose-dependently increased in astrocytes around blood vessels in the cerebral cortex and hippocampus in six weeks old offspring, indicative of reactive astrogliosis. Also enlarged lysosomal granules were observed in brain perivascular macrophages (PVMs) in the prenatally exposed offspring. The number of parvalbumin-positive interneurons and the expression levels of parvalbumin were decreased in the motor and prefrontal cortices at weaning and 120 days of age in the prenatally exposed offspring. In the open field test, behaviour was dose-dependently altered following maternal exposure to Printex 90, at 90 days of age. Prenatally exposed female offspring moved a longer total distance, and especially males spent significantly longer time in the central zone of the maze. In the offspring, the described effects were long-lasting as they were present at all time points investigated. CONCLUSION: The present study reports for the first time that maternal inhalation exposure to Printex 90 carbon black induced dose-dependent denaturation of PVM and reactive astrocytes, similarly to the findings observed following maternal exposure to Printex 90 by airway instillation. Of note, some of the observed effects have striking similarities with those observed in mouse models of neurodevelopmental disorders.


Assuntos
Encéfalo/efeitos dos fármacos , Exposição por Inalação/efeitos adversos , Exposição Materna/efeitos adversos , Nanopartículas/toxicidade , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Fuligem/toxicidade , Animais , Comportamento Animal/efeitos dos fármacos , Encéfalo/crescimento & desenvolvimento , Relação Dose-Resposta a Droga , Feminino , Proteína Glial Fibrilar Ácida/biossíntese , Macrófagos/efeitos dos fármacos , Macrófagos/patologia , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos Endogâmicos , Atividade Motora/efeitos dos fármacos , Gravidez
14.
Int J Pharm ; 550(1-2): 114-122, 2018 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-30125651

RESUMO

The lungs have potential as a means of systemic drug delivery of macromolecules. Systemic delivery requires crossing of the air-blood barrier, however with molecular size-dependent limitations in lung absorption of large molecules. Systemic availability after inhalation can be improved by absorption enhancers, such as bile salts. Enhancers may potentially interfere with the different constituents of the lungs, e.g. the lung surfactant lining the alveoli or the lung epithelium. We used two in vitro models to investigate the potential effects of bile salts on lung surfactant function (with the constrained drop surfactometer) and on the epithelium in the proximal airways (with the MucilAir™ cell system), respectively. In addition, we measured direct effects on respiration in mice inhaling bile salt aerosols. The bile salts inhibited lung surfactant function at different dose levels, however they did not affect the integrity of ciliated cells at the tested doses. Furthermore, the bile salt aerosols induced changes in the breathing pattern of mice indicative of pulmonary irritation. The bile salts were ranked according to potency in vitro for surfactant function disruption and in vivo for induction of pulmonary irritation. The ranking was the same, suggesting a correlation between the interference with lung surfactant and the respiratory response.


Assuntos
Ácidos e Sais Biliares , Sistemas de Liberação de Medicamentos , Administração por Inalação , Aerossóis , Animais , Ácidos e Sais Biliares/administração & dosagem , Ácidos e Sais Biliares/química , Epitélio/efeitos dos fármacos , Pulmão/efeitos dos fármacos , Masculino , Camundongos , Surfactantes Pulmonares/antagonistas & inibidores
15.
Mutagenesis ; 33(3): 253-261, 2018 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-30124895

RESUMO

Particles from burning candles contribute to the overall indoor exposure to particulate matter (PM). However, little is known about the effects of indoor sources of particles on cardiovascular disease endpoints. This study investigated the effect of pulmonary exposure to particles from combustion of candles and progression of atherosclerosis. Telomere shortening was assessed in tissues due to its relationship to risk of cardiovascular diseases. The particles were collected from burning candles and used for toxicological studies in cultured endothelial cells and apolipoprotein E (ApoE) knockout mice. Three hours exposure to particles increased the production of reactive oxygen species in endothelial cells, whereas there was no effect on cytotoxicity. Intratracheal instillation of particles (0.5 or 5 mg/kg) once a week for 5 weeks in ApoE-/- mice was associated with an accelerated progression of atherosclerosis in aorta and telomere shortening in the lung and spleen, whereas there was no effect on inflammation in the lungs (i.e. cell numbers), cell damage (i.e. lactate dehydrogenase) and lung barrier damage (i.e. protein concentration) as measured in bronchoalveolar lavage fluid. The results indicate that particles from burning candles are hazardous and this indoor emission source is an important contribution to the health risk of exposure to PM.


Assuntos
Poluentes Atmosféricos/efeitos adversos , Apolipoproteínas E/genética , Aterosclerose/genética , Encurtamento do Telômero/efeitos dos fármacos , Poluentes Atmosféricos/química , Animais , Aorta/efeitos dos fármacos , Aorta/patologia , Aterosclerose/fisiopatologia , Humanos , Pulmão/efeitos dos fármacos , Camundongos , Camundongos Knockout , Estresse Oxidativo/efeitos dos fármacos , Tamanho da Partícula , Material Particulado/efeitos adversos , Material Particulado/química , Placa Aterosclerótica/patologia , Espécies Reativas de Oxigênio/metabolismo , Encurtamento do Telômero/genética
16.
Environ Mol Mutagen ; 59(6): 539-548, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29761929

RESUMO

Firefighting is regarded as possibly carcinogenic, although there are few mechanistic studies on genotoxicity in humans. We investigated exposure to polycyclic aromatic hydrocarbons (PAH), lung function, systemic inflammation and genotoxicity in peripheral blood mononuclear cells (PBMC) of 22 professional firefighters before and after a 24-h work shift. Exposure was assessed by measurements of particulate matter (PM), PAH levels on skin, urinary 1-hydroxypyrene (1-OHP) and self-reported participation in fire extinguishing activities. PM measurements indicated that use of personal protective equipment (PPE) effectively prevented inhalation exposure, but exposure to PM occurred when the environment was perceived as safe and the self-contained breathing apparatuses were removed. The level of PAH on skin and urinary 1-OHP concentration were similar before and after the work shift, irrespective of self-reported participation in fire extinction activities. Post-shift, the subjects had reduced levels of oxidatively damaged DNA in PBMC, and increased plasma concentration of vascular cell adhesion molecule 1 (VCAM-1). The subjects reporting participation in fire extinction activities during the work shift had a slightly decreased lung function, increased plasma concentration of VCAM-1, and reduced levels of oxidatively damaged DNA in PBMC. Our results suggest that the firefighters were not exposed to PM while using PPE, but exposure occurred when PPE was not used. The work shift was not associated with increased levels of genotoxicity. Increased levels of VCAM-1 in plasma were observed. Environ. Mol. Mutagen. 59:539-548, 2018. © 2018 Wiley Periodicals, Inc.


Assuntos
Inflamação/etiologia , Leucócitos Mononucleares/efeitos dos fármacos , Pulmão/efeitos dos fármacos , Mutagênicos/efeitos adversos , Exposição Ocupacional/efeitos adversos , Hidrocarbonetos Policíclicos Aromáticos/efeitos adversos , Adulto , Poluentes Ocupacionais do Ar/efeitos adversos , Poluentes Ocupacionais do Ar/análise , Ensaio Cometa , Dano ao DNA/efeitos dos fármacos , Bombeiros , Humanos , Exposição por Inalação/efeitos adversos , Exposição por Inalação/análise , Leucócitos Mononucleares/metabolismo , Pulmão/fisiologia , Masculino , Pessoa de Meia-Idade , Mutagênicos/análise , Exposição Ocupacional/análise , Oxirredução/efeitos dos fármacos , Material Particulado/efeitos adversos , Material Particulado/análise , Hidrocarbonetos Policíclicos Aromáticos/análise
17.
J Nanopart Res ; 20(2): 48, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29497347

RESUMO

Fume hoods are one of the most common types of equipment applied to reduce the potential of particle exposure in laboratory environments. A number of previous studies have shown particle release during work with nanomaterials under fume hoods. Here, we assessed laboratory workers' inhalation exposure during synthesis and handling of CuO, TiO2 and ZnO in a fume hood. In addition, we tested the capacity of a fume hood to prevent particle release to laboratory air during simulated spillage of different powders (silica fume, zirconia TZ-3Y and TiO2). Airborne particle concentrations were measured in near field, far field, and in the breathing zone of the worker. Handling CuO nanoparticles increased the concentration of small particles (< 58 nm) inside the fume hood (up to 1 × 105 cm-3). Synthesis, handling and packaging of ZnO and TiO2 nanoparticles did not result in detectable particle release to the laboratory air. Simulated powder spills showed a systematic increase in the particle concentrations inside the fume hood with increasing amount of material and drop height. Despite powder spills were sometimes observed to eject into the laboratory room, the spill events were rarely associated with notable release of particles from the fume hood. Overall, this study shows that a fume hood generally offers sufficient exposure control during synthesis and handling of nanomaterials. An appropriate fume hood with adequate sash height and face velocity prevents 98.3% of particles release into the surrounding environment. Care should still be made to consider spills and high cleanliness to prevent exposure via resuspension and inadvertent exposure by secondary routes.

18.
J Occup Environ Hyg ; 15(5): D38-D43, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29494272

RESUMO

In conceptual exposure models, the transmission of pollutants in an imperfectly mixed room is usually described with general ventilation multipliers. This is the approach used in the Advanced REACH Tool (ART) and Stoffenmanager® exposure assessment tools. The multipliers used in these tools were reported by Cherrie (1999; http://dx.doi.org/10.1080/104732299302530 ) and Cherrie et al. (2011; http://dx.doi.org/10.1093/annhyg/mer092 ) who developed them by positing input values for a standard Near-Field/Far-Field (NF/FF) model and then calculating concentration ratios between NF and FF concentrations. This study revisited the calculations that produce the multipliers used in ART and Stoffenmanager and found that the recalculated general ventilation multipliers were up to 2.8 times (280%) higher than the values reported by Cherrie (1999) and the recalculated NF and FF multipliers for 1-hr exposure were up to 1.2 times (17%) smaller and for 8-hr exposure up to 1.7 times (41%) smaller than the values reported by Cherrie et al. (2011). Considering that Stoffenmanager and the ART are classified as higher-tier regulatory exposure assessment tools, the errors is general ventilation multipliers should not be ignored. We recommend revising the general ventilation multipliers. A better solution is to integrate the NF/FF model to Stoffenmanager and the ART.


Assuntos
Poluição do Ar em Ambientes Fechados/análise , Modelos Teóricos , Ventilação/normas , Poluentes Ocupacionais do Ar , Monitoramento Ambiental/métodos , Exposição Ocupacional/análise
19.
J Hazard Mater ; 341: 218-227, 2018 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-28780436

RESUMO

Here, we studied the particle release rate during Electrostatic spray deposition of anatase-(TiO2)-based photoactive coating onto tiles and wallpaper using a commercially available electrostatic spray device. Spraying was performed in a 20.3m3 test chamber while measuring concentrations of 5.6nm to 31µm-size particles and volatile organic compounds (VOC), as well as particle deposition onto room surfaces and on the spray gun user hand. The particle emission and deposition rates were quantified using aerosol mass balance modelling. The geometric mean particle number emission rate was 1.9×1010s-1 and the mean mass emission rate was 381µgs-1. The respirable mass emission-rate was 65% lower than observed for the entire measured size-range. The mass emission rates were linearly scalable (±ca. 20%) to the process duration. The particle deposition rates were up to 15h-1 for <1µm-size and the deposited particles consisted of mainly TiO2, TiO2 mixed with Cl and/or Ag, TiO2 particles coated with carbon, and Ag particles with size ranging from 60nm to ca. 5µm. As expected, no significant VOC emissions were observed as a result of spraying. Finally, we provide recommendations for exposure model parameterization.

20.
Mutagenesis ; 33(1): 105-115, 2018 02 24.
Artigo em Inglês | MEDLINE | ID: mdl-29045708

RESUMO

This study investigated a number of biomarkers, associated with systemic inflammation as well as genotoxicity, in 53 young and healthy subjects participating in a course to become firefighters, while wearing personal protective equipment (PPE). The exposure period consisted of a 3-day training course where the subjects participated in various live-fire training exercises. The subjects were instructed to extinguish fires of either wood or wood with electrical cords and mattresses. The personal exposure was measured as dermal polycyclic aromatic hydrocarbon (PAH) concentrations and urinary excretion of 1-hydroxypyrene (1-OHP). The subjects were primarily exposed to particulate matter (PM) in by-stander positions, since the self-contained breathing apparatus effectively prevented pulmonary exposure. There was increased dermal exposure to pyrene (68.1%, 95% CI: 52.5%, 83.8%) and sum of 16 polycyclic aromatic hydrocarbons (Æ©PAH; 79.5%, 95% CI: 52.5%, 106.6%), and increased urinary excretion of 1-OHP (70.4%, 95% CI: 52.5%; 106.6%) after the firefighting exercise compared with the mean of two control measurements performed 2 weeks before and 2 weeks after the firefighting course, respectively. The level of Fpg-sensitive sites in peripheral blood mononuclear cells (PBMCs) was increased by 8.0% (95% CI: 0.02%, 15.9%) compared with control measurements. The level of DNA strand breaks was positively associated with dermal exposure to pyrene and Æ©PAHs, and urinary excretion of 1-OHP. Fpg-sensitive sites were only associated positively with PAHs. Biomarkers of inflammation and lung function showed no consistent response. In summary, the study demonstrated that PAH exposure during firefighting activity was associated with genotoxicity in PBMCs.


Assuntos
Dano ao DNA/efeitos dos fármacos , Bombeiros , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/metabolismo , Exposição Ocupacional/efeitos adversos , Hidrocarbonetos Policíclicos Aromáticos/toxicidade , Adulto , Biomarcadores , Estudos Cross-Over , Ensaio de Imunoadsorção Enzimática , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Voluntários Saudáveis , Humanos , Mediadores da Inflamação/sangue , Exposição por Inalação , Masculino , Testes de Função Respiratória , Pele/química , Pele/efeitos dos fármacos , Urinálise , Adulto Jovem
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