Pulmonary instillation of low doses of titanium dioxide nanoparticles in mice leads to particle retention and gene expression changes in the absence of inflammation

AbstractWe investigated gene expression, protein synthesis, and particle retention in mouse lungs following intratracheal instillation of varying doses of nano-sized titanium dioxide (nano-TiO2). Female C57BL/6 mice were exposed to rutile nano-TiO2 via single intratracheal instillations of 18, 54, and 162μg/mouse. Mice were sampled 1, 3, and 28days post-exposure. The deposition of nano-TiO2 in the lungs was assessed using nanoscale hyperspectral microscopy. Biological responses in the pulmonary system were analyzed using DNA microarrays, pathway-specific real-time RT-PCR (qPCR), gene-specific qPCR arrays, and tissue protein ELISA. Hyperspectral mapping showed dose-dependent retention of nano-TiO2 in the lungs up to 28days post-instillation. DNA microarray analysis revealed approximately 3000 genes that were altered across all treatment groups (±1.3 fold; p<0.1). Several inflammatory mediators changed in a dose- and time-dependent manner at both the mRNA and protein level. Although no influx of neutrophils was detected at the low dose, changes in the expression of several genes and proteins associated with inflammation were observed. Resolving inflammation at the medium dose, and lack of neutrophil influx in the lung fluid at the low dose, were associated with down-regulation of genes involved in ion homeostasis and muscle regulation. Our gene expression results imply that retention of nano-TiO2 in the absence of inflammation over time may potentially perturb calcium and ion homeostasis, and affect smooth muscle activities

Nanotitanium dioxide toxicity in mouse lung is reduced in sanding dust from paint

<p>Abstract</p> <p>Background</p> <p>Little is known of how the toxicity of nanoparticles is affected by the incorporation in complex matrices. We compared the toxic effects of the titanium dioxide nanoparticle UV-Titan L181 (NanoTiO₂), pure or embedded in a paint matrix. We also compared the effects of the same paint with and without NanoTiO₂.</p> <p>Methods</p> <p>Mice received a single intratracheal instillation of 18, 54 and 162 μg of NanoTiO₂or 54, 162 and 486 μg of the sanding dust from paint with and without NanoTiO₂. DNA damage in broncheoalveolar lavage cells and liver, lung inflammation and liver histology were evaluated 1, 3 and 28 days after intratracheal instillation. Printex 90 was included as positive control.</p> <p>Results</p> <p>There was no additive effect of adding NanoTiO₂to paints: Therefore the toxicity of NanoTiO₂was reduced by inclusion into a paint matrix. NanoTiO₂induced inflammation in mice with severity similar to Printex 90. The inflammatory response of NanoTiO₂and Printex 90 correlated with the instilled surface area. None of the materials, except of Printex 90, induced DNA damage in lung lining fluid cells. The highest dose of NanoTiO₂caused DNA damage in hepatic tissue 1 day after intratracheal instillation. Exposure of mice to the dust from paints with and without TiO₂was not associated with hepatic histopathological changes. Exposure to NanoTiO₂or to Printex 90 caused slight histopathological changes in the liver in some of the mice at different time points.</p> <p>Conclusions</p> <p>Pulmonary inflammation and DNA damage and hepatic histopathology were not changed in mice instilled with sanding dust from NanoTiO₂paint compared to paint without NanoTiO₂. However, pure NanoTiO₂caused greater inflammation than NanoTiO₂embedded in the paint matrix.</p

Cardiovascular health effects following exposure of human volunteers during fire extinction exercises

Abstract Background Firefighters have increased risk of cardiovascular disease and of sudden death from coronary heart disease on duty while suppressing fires. This study investigated the effect of firefighting activities, using appropriate personal protective equipment (PPE), on biomarkers of cardiovascular effects in young conscripts training to become firefighters. Methods Healthy conscripts (n = 43) who participated in a rescue educational course for firefighting were enrolled in the study. The exposure period consisted of a three-day training course where the conscripts participated in various firefighting exercises in a constructed firehouse and flashover container. The subjects were instructed to extinguish fires of either wood or wood with electrical cords and mattresses. The exposure to particulate matter (PM) was assessed at various locations and personal exposure was assessed by portable PM samplers and urinary excretion of 1-hydroxypyrene. Cardiovascular measurements included microvascular function and heart rate variability (HRV). Results The subjects were primarily exposed to PM in bystander positions, whereas self-contained breathing apparatus effectively abolished pulmonary exposure. Firefighting training was associated with elevated urinary excretion of 1-hydroxypyrene (105%, 95% CI: 52; 157%), increased body temperature, decreased microvascular function (−18%, 95% CI: -26; −9%) and altered HRV. There was no difference in cardiovascular measurements for the two types of fires. Conclusion Observations from this fire extinction training show that PM exposure mainly occurs in situations where firefighters removed the self-contained breathing apparatus. Altered cardiovascular disease endpoints after the firefighting exercise period were most likely due to complex effects from PM exposure, physical exhaustion and increased core body temperature

Epoxy composite dusts with and without carbon nanotubes cause similar pulmonary responses, but differences in liver histology in mice following pulmonary deposition

Inorganic chemical composition given as elemental weight% measured by standardless WDXRF. The three epoxy materials were measured as solid disks (4 cm in diameter, 1 cm high). For comparison, the results for CNT powder, previously published in [25], were added to the figure. Displayed axis 99.7 – 100 %. (PPTX 71 kb

Acute and subacute pulmonary toxicity and mortality in mice after intratracheal instillation of ZnO nanoparticles in three laboratories

Inhalation is the main pathway of ZnO exposure in the occupational environment but only few studies have addressed toxic effects after pulmonary exposure to ZnO nanoparticles (NP). Here we present results from three studies of pulmonary exposure and toxicity of ZnO NP in mice. The studies were prematurely terminated because interim results unexpectedly showed severe pulmonary toxicity. High bolus doses of ZnO NP (25 up to 100μg; ≥1.4mg/kg) were clearly associated with a dose dependent mortality in the mice. Lower doses (≥6μg; ≥0.3mg/kg) elicited acute toxicity in terms of reduced weight gain, desquamation of epithelial cells with concomitantly increased barrier permeability of the alveolar/blood as well as DNA damage. Oxidative stress was shown via a strong increase in lipid peroxidation and reduced glutathione in the pulmonary tissue. Two months post-exposure revealed no obvious toxicity for 12.5 and 25μg on a range of parameters. However, mice that survived a high dose (50μg; 2.7mg/kg) had an increased pulmonary collagen accumulation (fibrosis) at a similar level as a high bolus dose of crystalline silica. The recovery from these toxicological effects appeared dose-dependent. The results indicate that alveolar deposition of ZnO NP may cause significant adverse health effects

A Comprehensive Review

Funding: This project has received funding from the European Unions’ Horizon 2020 research and innovation Programme under grant agreement No 733032. HBM4EU.Polycyclic aromatic hydrocarbons (PAHs) are among the chemicals with proven impact on workers' health. The use of human biomonitoring (HBM) to assess occupational exposure to PAHs has become more common in recent years, but the data generated need an overall view to make them more usable by regulators and policymakers. This comprehensive review, developed under the Human Biomonitoring for Europe (HBM4EU) Initiative, was based on the literature available from 2008-2022, aiming to present and discuss the information on occupational exposure to PAHs, in order to identify the strengths and limitations of exposure and effect biomarkers and the knowledge needs for regulation in the workplace. The most frequently used exposure biomarker is urinary 1-hydroxypyrene (1-OH-PYR), a metabolite of pyrene. As effect biomarkers, those based on the measurement of oxidative stress (urinary 8-oxo-dG adducts) and genotoxicity (blood DNA strand-breaks) are the most common. Overall, a need to advance new harmonized approaches both in data and sample collection and in the use of appropriate biomarkers in occupational studies to obtain reliable and comparable data on PAH exposure in different industrial sectors, was noted. Moreover, the use of effect biomarkers can assist to identify work environments or activities of high risk, thus enabling preventive risk mitigation and management measures.publishersversionpublishe