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The alveolar epithelium of the lung is by far the most permeable epithelial barrier of the human body. The risk for adverse effects by inhaled nanoparticles (NPs) depends on their hazard (negative action on cells and organism) and on exposure (concentration in the inhaled air and pattern of deposition in the lung). With the development of advanced...
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... Due to limited evidence about possible 3-MCPD toxicity, all latest published paper revealed that the 3-MCPD possesses serious effects on neurological toxicity and nephrotoxicity [76][77][78] Moreover, the in vivo study provides a better overview on the effects of 3-MCPD towards the human body as it is a directly dosing method, easy to perform and have complex multicellular response [79]. The most identified target organs in the in vivo study are the kidneys where 3-MCPD often causes renal alterations. ...
3-Monochloropropane-1,2-diol (3-MCPD) is one of the most common food contaminants in processed oils which forms mostly during the deodorization step of edible oil refining process. It has been detected in many types of food products such as infant formula, margarine, bread and soy sauce, which could result in kidney and testicular damage. The presence of 3-MCPD contaminant have been occurring for more a decade, which warrants a maximum permissible amount of 2 µg/kg body weight in food products in national and international levels. The purpose of this review is to provide an overview in the past 12 years on its physicochemical properties, occurrence, potential precursors and formation mechanism of 3-MCPD in foodstuffs. The toxicity, its quantification methods and mitigation strategy are also reviewed with an emphasis on the applicability, efficiency and issues encountered during the analysis. This review provides an elucidation regarding 3-MCPDEs and their food safety implications.
... In addition, particles less than 20 µm, when reaching the bloodstream, can be phagocyted by macrophages [7]. Due to their anatomical differences, animal models may not reflect reliably what occurs when humans are exposed to these particles [8]. ...
Microparticulate systems such as microparticles, microspheres, microcapsules or any particle in a micrometer scale (usually of 1–1000 µm) are widely used as drug delivery systems, because they offer higher therapeutic and diagnostic performance compared to conventional drug delivery forms. These systems can be manufactured with many raw materials, especially polymers, most of which have been effective in improving the physicochemical properties and biological activities of active compounds. This review will focus on the in vivo and in vitro application in the last decade (2012 to 2022) of different active pharmaceutical ingredients microencapsulated in polymeric or lipid matrices, the main formulation factors (excipients and techniques) and mostly their biological activities, with the aim of introducing and discussing the potential applicability of microparticulate systems in the pharmaceutical field.
... It is believed that the nasal olfactory pathway is key as a gateway entry because through it, inhaled NPs are able to reach the nerves of the trigeminal, brainstem and hippocampus. 88 Based on their size, the probability that the NPs reach the alveoli is maximal at approximately 20 nm, while probabilities of deposition in the alveoli for smaller and larger NPs reduce according to the classical model of the International Commission for 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 21 Radiological Protection (ICRP). The olfactory nerve provides a route (nose to brain) for the transport of xenobiotics, including particles, to the CNS that circumvent the protective BBB. ...
According to the World Health Organization, both indoor and urban air pollution are killing around 3.5 million people each year. During the last decades, the interest on understanding the composition...
... In case of asthma, the target site is lungs with the entire airways formed by alveolar and goblet cells with bronchiole cells containing bronchial epithelial Clara cells. The air-blood barrier within lungs consists of epithelial and endothelial tissues with attached basement membrane [106]. These structural peculiarities of lungs make it a better candidate for systemic and novel drug delivery target. ...
Asthma is considered as one of the most prevalent chronic respiratory alignment with subsequent airway inflammation mostly due to genetic predisposition and antigen allergies as associated factor. Treatments of asthma with synthetic drugs have laggings like side effects. Hence, alternative drugs are required for its treatment. The plant‐based compounds are widely utilitarian in regulation of asthma since ancient era due to negligible side effects, higher efficacy rate, and cost effectiveness. The main issue in use of these herbal compounds in drug formulation lie in its altered biocompatibility. In this panorama, several pharmaceutics have taken keen interest in searching novel drug delivery systems. Nanodrug delivery system using herbal compounds to treat asthma has proven to be an efficient mechanism. Traditional techniques used for herbal molecules delivery have disadvantages including critical biocompatibility, difficulty in absorption, poor target‐specific delivery, larger molecular weight, and retardation in crossing biological barriers. These can be extenuated by use of nanotechnology. Since use of herbal ingredient is in extremity with harmonious compatibility to be fabricated with nanocarriers, nanoparticles can be used for integration with herbal ingredients to ameliorate the technique and contravening asthma by reaching at target site with minimum effective level doses. The present study foregrounds current scenario related to treatment of asthma, mechanism involved in asthma physiopathology and epidemiology, nanoherbal in asthma drug delivery system, their delivery route, and efficiency. However, it could be opined that nanoherbal drug delivery is effective in treatment of asthma with easier dissolution without any toxicity or incompatibility.
... At the same time, cell culture and exposure conditions need to be as close as possible to the ones found in vivo. Several human in vitro models exist to represent specific areas of the respiratory tract such as nasal, tracheal, bronchial, and alveolar regions (Fröhlich and Salar-Behzadi 2014;Steimer, Haltner, and Lehr 2005). In order to accurately predict the effects of inhaled (nano)particles, an in vitro system needs to include the following features: (1) a suitable model mimicking the morphology and metabolic function of a particular healthy or vulnerable tissue/organ, and able to reproduce in vivo particle deposition patterns and clearance; ...
2023): Assessing the invitro toxicity of airborne (nano)particles to the human respiratory system: from basic to advanced models, Journal of Toxicology and Environmental Health, Part B, ABSTRACT Several studies have been conducted to address the potential adverse health risks attributed to exposure to nanoscale materials. While in vivo studies are fundamental for identifying the relationship between dose and occurrence of adverse effects, in vitro model systems provide important information regarding the mechanism(s) of action at the molecular level. With a special focus on exposure to inhaled (nano)particulate material toxicity assessment, this review provides an overview of the available human respiratory models and exposure systems for in vitro testing, advantages , limitations, and existing investigations using models of different complexity. A brief overview of the human respiratory system, pathway and fate of inhaled (nano)particles is also presented.
... Nanoparticles, compared with larger 10 μm particles trapped in the upper respiratory tract or 2.5 μm particles that settle in the lungs, can penetrate the secondary organs and, therefore, may present a higher risk for human health [23,24]. Other studies supporting these phenomena have also shown that macrophage clearance mechanisms in the lung remove harmful inhaled NPs less efficiently than larger particles [17,25,26]. However, according to the literature, it is not only the size that can play a role when assessing nanoparticle toxicity. ...
The concentration of nanoparticles in the ambient air can lead to induced toxicities; however, it appears that nanoparticles’ unique properties are completely omitted when assessing health risks. This paper aims to enhance the EPA health risk assessment by incorporating two new variables that consider the size of nanoparticles: the toxicity multiplier and the size multiplier. The former considers the qualitative aspect of the size of particles within a concentration, whilst the latter takes into account the effects associated with the number of particles of the specific i-th size distribution interval. To observe the impact of the new variables, a case study was performed. The studied element was cadmium, which was measured using ICP-MS to discover concentrations of size fractions, ranging from <15.1 to <9830 nm. Next, the cadmium concentration is assessed using both the current state-of-the-art method and the proposed method with adjustments. Based on the new approach, the final risk was 1.1 × 10−5, which was almost 24 times higher compared with the current method. The contribution of nanoparticles to the risk value grew from barely 6% to an alarming 88%. Therefore, the enhanced method can lead to more realistic results when assessing the health risks of nanoparticles.
... While too simplistic and not recapitulating neither the complexity of whole organisms nor the toxicokinetics [19] in vitro models offer many advantages. They permit different levels of study: organ, tissue, cell (one or several populations), they allow large screening of effects with a very small amount of test material and are very well adapted for the study of mechanisms, mainly for short term studies [17,20,21]. As they are performed under Forest et al. ...
Electronic cigarettes (or e-cigarettes) can be used as smoking cessation aid. Some studies tend to show that they are less hazardous than tobacco cigarettes, even if it does not mean they are completely safe. The huge variation in study designs assessing in vitro toxicity of e-cigarettes aerosol makes it difficult to make comparisons and draw robust and irrefutable conclusions. In this paper, we review this heterogeneity (in terms of e-cigarette products, biological models, and exposure conditions) with a special focus on the wide disparity in the doses used as well as in the way they are expressed. Finally, we discuss the major issue of dosimetry and show how dosimetry tools enable to align data between different exposure systems or data from different laboratories and therefore allow comparisons to help further exploring the risk potential of e-cigarettes.
... Depending on their aerodynamic diameter, airborne particles bigger than a few micrometers are deposited along the surface covered with mucus of the conducting airways by impaction, where they are rapidly removed via mucociliary clearance. Inhaled nanoparticles (NP) smaller than 100 nm in diameter deposit mainly by diffusion in the whole lung, but are especially efficient in the most distal and fragile parts of the lung, the alveoli [1]. While the alveolar region possesses over 90% of the lung's surface area, it also represents the most susceptible tissue interface to the environment with only a few 100 nm thickness of the alveolar walls, protected only by a thin liquid layer [2]. ...
Lung epithelial organoids for the hazard assessment of inhaled nanomaterials offer a promising improvement to in vitro culture systems used so far. Organoids grow in three-dimensional (3D) spheres and can be derived from either induced pluripotent stem cells (iPSC) or primary lung tissue stem cells from either human or mouse. In this perspective we will highlight advantages and disadvantages of traditional culture systems frequently used for testing nanomaterials and compare them to lung epithelial organoids. We also discuss the differences between tissue and iPSC-derived organoids and give an outlook in which direction the whole field could possibly go with these versatile tools.
... The rat is the alternative recommended by Organisation for Economic Co-operation and Development (OECD) because it is a more qualified model, easier to implement, and remains representative of the human respiratory system [23][24][25]. This animal model is preferred to the mouse model because it has more anatomical similarities with humans than with mice [26]. This animal model is the most commonly used to study the pulmonary toxicity of alumina particles. ...
Alumina nanoparticles (Al2O3 NPs) can be released in occupational environments in
different contexts such as industry, defense, and aerospace. Workers can be exposed by inhalation to these NPs, for instance, through welding fumes or aerosolized propellant combustion residues. Several clinical and epidemiological studies have reported that inhalation of Al2O3 NPs could trigger aluminosis, inflammation in the lung parenchyma, respiratory symptoms such as cough or shortness of breath, and probably long-term pulmonary fibrosis. The present review is a critical update of the current knowledge on underlying toxicological, molecular, and cellular mechanisms induced by exposure to Al2O3 NPs in the lungs. A major part of animal studies also points out inflammatory cells
and secreted biomarkers in broncho-alveolar lavage fluid (BALF) and blood serum, while in vitro studies on lung cells indicate contradictory results regarding the toxicity of these NPs.
... Respiratory sensitizing agents have been identified primarily using rodent inhalation studies. While these investigations are the current gold standard, they are not rapid and the costs associated with such bioassays is costly [7][8][9]. There is a need to develop alternative to animal models that can accurately and rapidly identify possible sensitizing agents. ...
Diisocyanates are commonly used in polyurethanes where use includes industrial, commercial, and residential applications and can exist as respirable contaminants. These respirable contaminants exist in the air we breathe. Yet, there is no rapid assay available to test for potential respiratory sensitizers. To assess these hazards, as well as to decrease animal numbers used in testing, investigations that lead to verifiable in vitro methods are needed. We describe an easy, reliable, verified cell culture model that can be adopted by any lab capable of performing molecular toxicology. The architecturally relevant alveolar model consists of epithelial cells, macrophage cells, and dendritic cells in a simply maintained submerged system ideal for high-throughput testing. Exposures to contaminants that verify biomarker identification include a known pulmonary sensitizer (isophorone diisocyanate) and a positive control for cellular activation (phorbol 12-myristate 13-acetate/ionomycin). The mitochondrial reactive oxygen species generation and cytostructural changes were assessed with confocal laser scanning microscopy; cell morphology was assessed with scanning electron microscopy; biochemical reactions were assessed via protein arrays; genetic alterations were assessed via gene arrays; and cell surface activation markers were assessed via flow cytometry. Results showed that compared to untreated cultures, isophorone diisocyanate increased markers for dendritic cell activation, trafficking, and antigen presentation; number and length of dendritic protrusions; oxidative stress; and genetic and cytokine expression of neutrophil chemoattractants. The chemokines and cytokines CCL7, CXCL5, IL-6, and IL-8 were identified as biomarkers indicative of respiratory sensitization. By including multiple methods to assess endpoints, the in vitro model described can serve as a high-throughput assay to identify substances which may lead to respiratory sensitization.
