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•QA/QC scores for NMP PBK experimental and modeling studies reveal limitations.•A practical guideline to establish a PBK model for NMP is provided.•A Probability Density Function ...framework for NMP data alignment is provided.•A fully aligned risk assessment framework for NMP in humans is provided.
Insufficient data on nano- and microplastics (NMP) hinder robust evaluation of their potential health risks. Methodological disparities and the absence of established toxicity thresholds impede the comparability and practical application of research findings. The diverse attributes of NMP, such as variations in sizes, shapes, and compositions, complicate human health risk assessment. Although probability density functions (PDFs) show promise in capturing this diversity, their integration into risk assessment frameworks is limited. Physiologically based kinetic (PBK) models offer a potential solution to bridge the gap between external exposure and internal dosimetry for risk evaluation. However, the heterogeneity of NMP poses challenges for accurate biodistribution modeling.
A literature review, encompassing both experimental and modeling studies, was conducted to examine biodistribution studies of monodisperse micro- and nanoparticles. The literature search in PubMed and Scopus databases yielded 39 studies that met the inclusion criteria. Evaluation criteria were adapted from previous Quality Assurance and Quality Control (QA-QC) studies, best practice guidelines from WHO (2010), OECD guidance (2021), and additional criteria specific to NMP risk assessment. Subsequently, a conceptual framework for a comprehensive NMP-PBK model was developed, addressing the multidimensionality of NMP particles.
Parameters for an NMP-PBK model are presented. QA-QC evaluations revealed that most experimental studies scored relatively well (>0) in particle characterizations and environmental settings but fell short in criteria application for biodistribution modeling. The evaluation of modeling studies revealed that information regarding the model type and allometric scaling requires improvement. Three potential applications of PDFs in PBK modeling of NMP are identified: capturing the multidimensionality of the NMP continuum, quantifying the probabilistic definition of external exposure, and calculating the bio-accessibility fraction of NMP in the human body. A framework for an NMP-PBK model is proposed, integrating PDFs to enhance the assessment of NMP’s impact on human health.
Studies investigating the relationship between exposure to air pollution and brain development using magnetic resonance images are emerging. However, most studies have focused only on prenatal ...exposures, and have included a limited selection of pollutants. Here, we aim to expand the current knowledge by studying pregnancy and childhood exposure to a wide selection of pollutants, and brain morphology in preadolescents.
We used data from 3133 preadolescents from a birth cohort from Rotterdam, the Netherlands (enrollment: 2002–2006). Concentrations of nitrogen oxides, coarse, fine, and ultrafine particles, and composition of fine particles were estimated for participant's home addresses in pregnancy and childhood, using land use regression models. Structural brain images were obtained at age 9–12 years. We assessed the relationships of air pollution exposure, with brain volumes, and surface-based morphometric data, adjusting for socioeconomic and life-style characteristics, using single as well as multi-pollutant approach.
No associations were observed between air pollution exposures and global volumes of total brain, and cortical and subcortical grey matter. However, we found associations between higher pregnancy and childhood air pollution exposures with smaller corpus callosum, smaller hippocampus, larger amygdala, smaller nucleus accumbens, and larger cerebellum (e.g. -69.2mm3 hippocampal volume 95%CI -129.1 to -9.3 per 1ng/m3 increase in pregnancy exposure to polycyclic aromatic hydrocarbons). Higher pregnancy exposure to air pollution was associated with smaller cortical thickness while higher childhood exposure was associated with predominantly larger cortical surface area.
Higher pregnancy or childhood exposure to several air pollutants was associated with altered volume of several brain structures, as well as with cortical thickness and surface area. Associations showed some similarity to delayed maturation and effects of early-life stress.
•Pregnancy and childhood air pollution was not associated with global volumes.•Air pollution was associated with smaller corpus callosum and hippocampus volumes.•Also associated with larger cerebellum, amygdala, and nucleus accumbens volumes.•Pregnancy and childhood air pollution was related to smaller cortical thickness.•Childhood air pollution was related to larger cortical surface.
Trace and major elements concentrations in PM10 and PM2.5 were measured at 20 sites spread in the Barcelona metropolitan area (1 rural background, 6 urban background, 13 road traffic sites) and at 1 ...reference site. Three 2-week samples per site and size fraction were collected during 2009 using low volume samplers, adding a total of 120 samples. Collected samples were analysed for elemental composition using Energy Dispersive X-ray fluorescence (XRF). EC, OC, and hopanes and steranes concentrations in PM2.5 were determined. Positive Matrix Factorisation (PMF) model was used for a source apportionment analysis. The work was performed as part of the ESCAPE project.
Elements were found in concentrations within the usual range in Spanish urban areas. Mineral elements were measured in higher concentrations during the warm season, due to enhanced resuspension; concentrations of fueloil combustion elements were also higher in summer. Elements in higher concentration at the traffic sites were: Ba, Cr, Cu, Fe, Mn, Mo, Pb, Sn, Zn and Zr. Spatial variations related to non-traffic sources were observed for concentrations of Br, Cl, K, and Na (sea salt origin) and Ni, V and S (shipping emissions), which were higher at the coastal sites, as well as for Zn and Pb, higher at sites closer to industrial facilities.
Five common sources for PM10 and PM2.5 were identified by PMF: road traffic (with tracers Ba, Cr, Cu, Fe, Mo and Zn); fueloil combustion (Ni and V); secondary sulphate; industry (Pb and Zn); and mineral source (Al, Ca, Mg, Si, Sr and Ti). A marine aerosol source, a mixture of sea salt with aged anthropogenic aerosols, was found only in PM10. EC, hopanes and steranes concentrations correlate strongly with the PM10 road traffic source contributions, being hence all attributed to the same source. OC may arise from other sources in addition to road traffic and have a high contribution of secondary OC.
Significant spatial and temporal variation in the PM2.5 and PM10 elemental composition was found. Spatial patterns differed per element, related to the main source. The identified source contributions can be used in health studies of source-specific particles.
•Trace and major elements PM10 and PM2.5 concentrations at 20 sites in Barcelona.•Ba, Cr, Cu, Fe, Mn, Mo, Pb, Sn, Zn and Zr in higher concentrations at traffic sites.•Spatial variations related to non-traffic sources observed for specific elements.•Sources: road traffic, fueloil combustion, sulphate, industry, mineral, marine.•Improved exposure assessment to be exploited by epidemiological studies.
The presence of microplastics in environmental compartments is generally recognized as a (potential) health risk. Many papers have been published on the abundance of microplastics at various ...locations around the globe, but only limited knowledge is available on possible mitigation routes. One of the mitigation routes is based on the choice of plastic materials used for products that may unintentionally end up in the environment. As a first approach, this paper presents a method to calculate the tendency of polymers to form microplastics, based on their mechanical and physical properties. A MicroPlastic Index (MPI) that correlates the microplastic formation to polymer properties is defined for both impact and wear of polymers via a theoretical particle size and the energy required to form these particles. A first comparison between calculated and experimental particle size is included. The MPI for impact and wear follow the same trend. Finally, these MPIs are correlated to the respective abundance of the microplastics in the environment, corrected for global production of the corresponding polymers: the higher the MPI, the more microplastics are found in the environment. Thus, the MPI can be used as a basis for choice or redesign of polymers to reduce microplastic formation.
Background: There is a strong need for laboratory in vitro test systems for the toxicity of airborne particulate matter and nanoparticles. The measurement of oxidative stress potential offers a ...promising way forward. Objectives:Aworkshop was convened involving leading workers from the field in order to review the available test methods and to generate a Consensus Statement. Discussions: Workshop participants summarised their own research activities as well as discussion the relative merits of different test methods. Conclusions: In vitro test methods have an important role to play in the screening of toxicity in airborne particulate matter and nanoparticles. In vitro cell challenges were preferable to in vitro acellular systems but both have a potential major role to play and offer large cost advantages relative to human or animal inhalation studies and animal in vivo installation experiments. There remains a need to compare tests one with another on standardised samples and also to establish a correlation with the results of population-based epidemiology.
Emissions from solid-fuel burning cookstoves are associated with 3 to 4 million premature deaths annually and contribute significantly to impacts on climate. Pellet-fueled gasifier stoves have some ...emission factors (EFs) approaching those of gas-fuel (liquid petroleum gas) stoves; however, their emissions have not been evaluated for biological effects. Here we used a new International Organization for Standardization (ISO) testing protocol to determine pollutant- and mutagenicity-EFs for a stove designed for pellet fuel, the Mimi Moto, and for two other forced-draft stoves, Xunda and Philips HD4012, burning pellets of hardwood or peanut hulls. The Salmonella assay-based mutagenicity-EFs (revertants/megajouledelivered) spanned three orders of magnitude and correlated highly (r = 0.99; n = 5) with EFs of the sum of 32 particle-phase polycyclic aromatic hydrocarbons (PAHs). The Mimi Moto/hardwood pellet combination had total-PAH- and mutagenicity-EFs 99.2 and 96.6% lower, respectively, compared to data published previously for the Philips stove burning non-pelletized hardwood, and 100 and 99.8% lower, respectively, compared to those of a wood-fueled three-stone fire. The Xunda burning peanut hull pellets had the highest fuel energy-based mutagenicity-EF (revertants/megajoulethermal) of the pellet stove/fuel combinations tested, which was between that of diesel exhaust, a known human carcinogen, and a natural-draft wood stove. Although the Mimi Moto burning hardwood pellets had the lowest fuel energy-based mutagenicity-EF, this value was between that of utility coal and utility wood boilers. This advanced stove/fuel combination has the potential to greatly reduce emissions in contrast to a traditional stove, but adequate ventilation is required to approach acceptable levels of indoor air quality.
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•Pellet cookstoves can be a clean energy solution for those reliant on solid fuels.•Here, five pellet cookstove/fuel combinations were assessed for PM mutagenicity.•Mutagenicity emission factors spanned 3 orders-of-magnitude & correlated with PAHs.•Cleanest combination was similar to utility boiler; dirtiest to that of diesel PM.•Pellet stoves can greatly reduce emissions, but adequate ventilation is required.
Micro- and nanoplastics have been detected in environmental compartments from the highest mountains to the deepest seas. They have been shown to be present at almost all trophic levels, and within ...humans they have been detected in numerous organs and human stool. Whilst their ubiquitous nature is indisputable, little is known about the health risks they may present. Much current research is focussed on the production of test materials with which to perform the necessary health studies. An important aspect of this is the correct storage and suspension of the materials to ensure they remain stable both chemically and with regards to size and shape. In this review, we look at the chemical stability of nine common polymers in a range of liquids; first with the use of commercial compatibility charts and then with a more quantitative approach using Hansen solubility parameters. We then look at stability with regards to particle agglomeration, whether and how stable compositions can be predicted, and which dispersants can be added to increase stability. Finally, we discuss the role of bio-surfactants and the eco-corona and how these may offer a route to both better stability and environmental relevance.
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•No “one size fits all” approach, different plastic types require different liquids.•Zeta potential and Hansen Solubility Parameter can predict stable suspensions.•Surfactants aid suspension stability but influence toxicity and uptake tests.•Biosurfactants may aid stability whilst also increasing environmental relevance.
Diesel emissions are the main source of air pollution in urban areas, and diesel exposure is linked with substantial adverse health effects. In vitro diesel exposure models are considered a suitable ...tool for understanding these effects. Here we aimed to use a controlled in vitro exposure system to whole diesel exhaust to study the effect of whole diesel exhaust concentration and exposure duration on mucociliary differentiated human primary bronchial epithelial cells (PBEC). PBEC cultured at the air-liquid interface were exposed for 60 to 375 min to three different dilutions of diesel exhaust (DE). The DE mixture was generated by an engine at 47% load, and characterized for particulate matter size and distribution and chemical and gas composition. Cytotoxicity and epithelial barrier function was assessed, as well as mRNA expression and protein release analysis. DE caused a significant dose-dependent increase in expression of oxidative stress markers (HMOX1 and NQO1; n = 4) at 6 h after 150 min exposure. Furthermore, DE significantly increased the expression of the markers of the integrated stress response CHOP and GADD34 and of the proinflammatory chemokine CXCL8, as well as release of CXCL8 protein. Cytotoxic effects or effects on epithelial barrier function were observed only after prolonged exposures to the highest DE dose. These results demonstrate the suitability of our model and that exposure dose and duration and time of analysis postexposure are main determinants for the effects of DE on differentiated primary human airway epithelial cells.
The diversity and increasing prevalence of products derived from engineered nanomaterials (ENM), warrants implementation of non‐animal approaches to health hazard assessment for ethical and practical ...reasons. Although non‐animal approaches are becoming increasingly popular, there are almost no studies of side‐by‐side comparisons with traditional in vivo assays. Here, transcriptomics is used to investigate mechanistic similarities between healthy/asthmatic models of 3D air–liquid interface (ALI) cultures of donor‐derived human bronchial epithelia cells, and mouse lung tissue, following exposure to copper oxide ENM. Only 19% of mouse lung genes with human orthologues are not expressed in the human 3D ALI model. Despite differences in taxonomy and cellular complexity between the systems, a core subset of matching genes cluster mouse and human samples strictly based on ENM dose (exposure severity). Overlapping gene orthologue pairs are highly enriched for innate immune functions, suggesting an important and maybe underestimated role of epithelial cells. In conclusion, 3D ALI models based on epithelial cells, are primed to bridge the gap between traditional 2D in vitro assays and animal models of airway exposure, and transcriptomics appears to be a unifying dose metric that links in vivo and in vitro test systems.
After exposure to copper oxide nanoparticles, the transcriptomes of 3D air–liquid interface cultures of human bronchial epithelial cells are compared to mouse lung tissues. Both models share an unprecedented functional core of 1936 differentially expressed gene orthologues, corresponding to 266 highly enriched pathways. The data increases knowledge that is relevant for regulatory validation of non‐animal alternative testing systems.
Recently, Sustainable Aviation Fuel (SAF) blends and novel combustion technologies have been introduced to reduce aircraft engine emissions. However, there is limited knowledge about the impact of ...combustion technology and fuel composition on toxicity of primary Particulate Matter (PM) emissions, comparable to regulated non-volatile PM (nvPM).
In this study, primary PM was collected on filters using a standardised approach, from both a Rich-Quench-Lean (RQL) combustion rig and a bespoke liquid fuelled Combustion Aerosol Standard (CAST) Generator burning 12 aviation fuels including conventional Jet-A, SAFs, and blends thereof. The fuels varied in aromatics (0–25.2%), sulphur (0–3000 ppm) and hydrogen (13.43–15.31%) contents. Toxicity of the collected primary PM was studied in vitro utilising Air-Liquid Interface (ALI) exposure of lung epithelial cells (Calu-3) in monoculture and co-culture with macrophages (differentiated THP-1 cells). Cells were exposed to PM extracted from filters and nebulised from suspensions using a cloud-based ALI exposure system. Toxicity readout parameters were analysed 24 h after exposure.
Results showed presence of genotoxicity and changes in gene expression at dose levels which did not induce cytotoxicity. DNA damage was detected through Comet assay in cells exposed to CAST generated samples. Real-Time PCR performed to investigate the expression profile of genes involved in oxidative stress and DNA repair pathways showed different behaviours after exposure to the various PM samples. No differences were found in pro-inflammatory interleukin-8 secretion. This study indicates that primary PM toxicity is driven by wider factors than fuel composition, highlighting that further work is needed to substantiate the full toxicity of aircraft exhaust PM inclusive of secondary PM emanating from numerous engine technologies across the power range burning conventional Jet-A and SAF.
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•Human lung cells were exposed to primary PM from combustion of aviation fuels.•Toxicity depended on combustion technology but did not correlate with fuel properties.•Genotoxicity induced even at the relatively low PM deposition doses.•Strategies of lowering aromatic content may result in less harmful PM emissions.
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