60 research outputs found
Cerium dioxide nanoparticles exacerbate house dust mite induced type II airway inflammation
No full textBackground
Nanomaterial inhalation represents a potential hazard for respiratory conditions such as asthma. Cerium dioxide nanoparticles (CeO2NPs) have the ability to modify disease outcome but have not been investigated for their effect on models of asthma and inflammatory lung disease. The aim of this study was to examine the impact of CeO2NPs in a house dust mite (HDM) induced murine model of asthma.
Results
Repeated intranasal instillation of CeO2NPs in the presence of HDM caused the induction of a type II inflammatory response, characterised by increased bronchoalveolar lavage eosinophils, mast cells, total plasma IgE and goblet cell metaplasia. This was accompanied by increases in IL-4, CCL11 and MCPT1 gene expression together with increases in the mucin and inflammatory regulators CLCA1 and SLC26A4. CLCA1 and SLC26A4 were also induced by CeO2NPs + HDM co-exposure in air liquid interface cultures of human primary bronchial epithelial cells. HDM induced airway hyperresponsiveness and airway remodelling in mice were not altered with CeO2NPs co-exposure. Repeated HMD instillations followed by a single exposure to CeO2NPs failed to produce changes in type II inflammatory endpoints but did result in alterations in the neutrophil marker CD177. Treatment of mice with CeO2NPs in the absence of HDM did not have any significant effects. RNA-SEQ was used to explore early effects 24 h after single treatment exposures. Changes in SAA3 expression paralleled increased neutrophil BAL levels, while no changes in eosinophil or lymphocyte levels were observed. HDM resulted in a strong induction of type I interferon and IRF3 dependent gene expression, which was inhibited with CeO2NPs co-exposure. Changes in the expression of genes including CCL20, CXCL10, NLRC5, IRF7 and CLEC10A suggest regulation of dendritic cells, macrophage functionality and IRF3 modulation as key early events in how CeO2NPs may guide pulmonary responses to HDM towards type II inflammation.
Conclusions
CeO2NPs were observed to modulate the murine pulmonary response to house dust mite allergen exposure towards a type II inflammatory environment. As this type of response is present within asthmatic endotypes this finding may have implications for how occupational or incidental exposure to CeO2NPs should be considered for those susceptible to disease
Evidence for the presence of a microsomal NADH-dependent enzyme system that can bioactivate aromatic amines in the liver of rats and mice
No full textStructure confirmation, reactivity, bacterial mutagenicity and quantification of 2,2,4-tribromo-5-hydroxycyclopent-4-ene-1,3-dione in drinking water
No full textAbstract The presence of two new disinfectant by-product (DBP) groups in the UK was recently shown using non-target analysis, halogenated-hydroxycyclopentenediones and halogenated-methanesulfonic acids. In this work, we confirmed the structure of 2,2,4-tribromo-5-hydroxycyclopent-4-ene-1,3-dione (TBHCD), and quantified it together with dibromomethanesulfonic acid at 122 ± 34 and 326 ± 157 ng L−1 on average in London’s drinking water, respectively (n = 21). We found TBHCD to be photolabile and unstable in tap water and at alkaline pH. Furthermore, spectral and computational data for TBHCD and three other halogenated-hydroxycyclopentenediones indicated they could act as a source of radicals in water and in the body. Importantly, TBHCD was calculated to have a 14.5 kcal mol−1 lower C-Br bond dissociation enthalpy than the N-Br bond of N-bromosuccinimide, a common radical substitution reagent used in organic synthesis. TBHCD was mutagenic in Salmonella/microsome assays using strains TA98, TA100 and TA102. This work reveals the unique features, activity and toxicity of trihalogenated hydroxycyclopent-4-ene-1,3-diones, prompting a need to more comprehensively assess their risks
Does urban chemical exposure influence the skewing of the immune system in Thai infants?
No full textIntroduction
Urbanisation and industrialisation have led to increased chemical pollution, potentially influencing infants' immune systems and allergies. This prospective cohort study aimed to investigate the impact of urban chemical exposure on the skewing of the immune system and allergy in Thai infants.
Methods
A pilot cohort of first-trimester pregnant women and infants born to them, attending Ramathibodi, Samut Prakan, and Rayong Hospitals in Thailand, was recruited. Their exposure to urban chemical pollutants was assessed via a self-assessment questionnaire (SAQ), estimated ambient PM2.5 exposure quantified by spatial interpolation of reported concentrations, and biomarkers (whole blood heavy metals; As, Cd, Cr, Hg, Mn, and Pb) by Inductively Coupled Plasma Mass Spectrometry (ICP-MS) in the first trimester, urine cotinine/creatinine ratio (CCR) across pregnancy and infancy (early-life). The outcomes included allergy (allergic diseases, sensitisation, and total IgE) and immunological profiles of infants (cytokines). Sensitisation was indicated by measuring specific IgE (sIgE) to common allergen. IgE and sIgE were analysed multiple times during pregnancy and the first year of life. Statistical analyses of correlations and univariate logistic regression and multivariable logistic regression with Bonferroni correction were conducted to determine associations between chemical exposure to immune system changes and allergic outcomes.
Results
Of 203 pregnant women, 86 maternal-child pairs were included in the analysis (sub-cohort study for this DPhil). Allergic diseases (allergic dermatitis; AD and food allergy; FA) were diagnosed in 24 infants (27.9%). There were no differences in sIgE and total IgE between individuals with and without allergies. Spearman’s correlation found both significant positive and negative associations of allergy and concentrations of infant cytokines (Interleukin (IL)-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-13, IL-22, IL-31, IL-33, interferon (IFN)-γ, tumour necrosis factor (TNF)-ꭤ, and thymic stromal lymphopoietin (TSLP)) with all of heavy metals except Cd and Pb, urine CCR, and PM2.5. Univariate logistic regression analysis found that prepregnancy body mass index (BMI), maternal occupation, maternal education, maternal sensitisation, sibling allergy, gravida, birth weight, child gender, exclusive breastfeeding, type of residence, home ventilation system (open door/window, fan), air conditioner (AC) use, air purifier use, recently furnished, mould visibility at home, pet exposure, environmental tobacco smoke (ETS) exposure, season of data collection, birth season, Pb exposure, PM2.5 exposure, and IL-12/IL-23 p40 concentration were significantly associated with allergic outcomes. Multivariable logistic regression analysis with Bonferroni correction and hospital (site of data collection) adjustment found that home ventilation (open door/window), using air purifier, visible mould, household ETS, and maternal sensitisation were significant associated with allergic outcome in infant children.
Conclusions
This study found statistically significant association between early-life exposure to urban environments and an increased risk of allergies (AD and FA) and immune skewing in Thai infants. These factors included residence type, ventilation practices, heavy metal exposure, environmental tobacco smoke, and household ETS. Exposure to urban pollution, including heavy metals, ETS, and PM2.5 also significantly correlated with the production of critical cytokines related to allergies and inflammation, depending on the timing of exposure from pregnancy to infancy. These findings will help to inform public health strategies and policies for reducing environmental health risks in these and similar urban environments
Identification of Novel Simulants for Toxic Industrial Chemicals and Chemical Warfare Agents for Human Decontamination Studies: A Systematic Review and Categorisation of Physicochemical Characteristics
No full textChemical simulants have long been used in human trials of mass decontamination to determine the efficacy of decontamination interventions against more toxic agents. Until now, reliance has mostly been on individual chemicals as surrogates to specific agents (e.g., methyl salicylate for sulphur mustard). A literature review was conducted to identify chemicals that had been previously tested on human volunteers and that represent diverse physicochemical characteristics in order to create a repository for chemical simulants. Of the 171 unique chemicals identified, 78 were discounted for the risk they could pose to human volunteers, 39 were deemed suitable for use, and a further 54 were considered to be possible simulants but would require further research. Suitable simulants included both solid and liquid chemicals spanning a wide range of physicochemical properties including molecular weight, octanol/water partition coefficient, vapour pressure, and solubility. This review identifies an array of potential simulants suitable for use in human volunteer decontamination studies and is of relevance to future studies on systemic absorption and surface decontamination
AN IMPROVED NON-TARGET ANALYSIS AND SUSPECT SCREENING WORKFLOW FOR ORGANIC ACID CONTAMINANTS IN DRINKING WATER
No full textA novel and generalisable analytical workflow for non-target analysis (NTA) and suspect screening (SS) of potentially toxic organic acids in drinking water is presented, featuring selective extraction by silica-based strong anion exchange solid-phase extraction (SAX-SPE), mixed-mode liquid chromatography-high resolution mass spectrometric (LC-HRMS) analysis, non-targeted peak detection, features reduction and SS. To achieve this, a selection of 23 structurally diverse compounds with a broad range of polarities were evaluated. Importantly, the novel introduction of an elution solvent containing ammonium bicarbonate extended the current applicability of SAX-SPE for strong acids and subsequent mass spectrometry analysis. This new method performed with consistently higher recovery (88 ± 7 % at 500 ng L-1), improved selectivity and lower matrix interference (mean = 12%) over a generic mixed-mode weak anion exchange SPE method. In addition, a novel filter for reducing full-scan features from fulvic and humic acids was successfully introduced, reducing workload and potential for false positives. The workflow was then applied to NTA/SS of 10 London municipal drinking water samples, allowing the identification of 22 confirmed substances. Several poorly investigated and potentially harmful compounds were found. In particular, predicted mutagenicity and occurrence frequency indicated the need for further investigation of halogenated hydroxy-cyclopentene-diones (HCDs) and dibromomethanesulfonic acid in drinking water. Overall, this approach demonstrated that employing some selectivity for general molecular properties in NTA overall helped shortlist suspect and potentially toxic chemical contaminants with higher confidence, in this case for organic acids
Exposure to nanomaterials in consumer spray products available in the UK
No full textProducts containing nanomaterials (NMs) (size < 100 nanometres) are rapidly entering the market, however little is known about inhalation exposures to NMs from their use. Here, we analysed representative consumer spray products available in the UK that claim (or are expected) to contain NMs, to assess potential NM exposure levels during use. In the absence of a UK-focused product inventory, we searched “The Nanodatabase” (nanodb.dk), which listed 269 (out of 3001) products for which inhalation was identified as an exposure pathway. None were available over-the-counter at large stores, but 40 were available on “.co.uk” websites (mainly Amazon). We obtained a representative sample (based on product type and claimed content e.g. silver, silica, gold) and found that 12 out of 16 products contained detectable NMs. We used a multi-method approach to characterise the NMs; inductively-coupled plasma mass spectrometry (ICP-MS), ultraviolet-visible spectroscopy and energy-dispersive x-ray spectroscopy to assess NM composition, and dynamic light scattering, nanoparticle tracking analysis, transmission electron microscopy and single particle ICP-MS to determine particle size and shape. The sizes of the airborne particles/droplets produced by spraying a sub-set (6) of these products were measured using aerodynamic and mobility particle sizers, demonstrating the presence of inhalable aerosols. Whilst 5 out of 6 products clearly contained NMs, only 3 produced aerosols in the nano-size range, suggesting that other constituents (e.g. solvent, fragrance) make up the bulk of the aerosol mass. Using the data generated, quantities of NMs inhaled when using these products can be estimated, which is important for appropriate risk characterisation
Effects of nicotine and E-cigarette fluids on cytochromes P450 in hCMEC/D3 blood-brain barrier cell line
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