Is pulmonary inflammation a valid predictor of particle induced lung pathology? The case of amorphous and crystalline silicas.

Although inflammation is a normal and beneficial response, it is also a key event in the pathology of many chronic diseases, including pulmonary and systemic particle-induced disease. In addition, inflammation is now considered as the key response in standard settings for inhaled particles and a critical endpoint in OECD-based sub-acute/ chronic animal inhalation testing protocols. In this paper, we discuss that whilst the role of inflammation in lung disease is undeniable, it is when inflammation deviates from normal parameters that adversity occurs.

Talc Inhalation in Rats and Humans: A Review and Appraisal of Available Evidence.

Background: Current information on the health effects and toxicology of talc suggests that this may lead to a specific target organ toxicity arising from repeated exposure (STOT-RE) classification.

Objective: To provide an assessment of the currently available inhalation toxicity data on talc and to put these data in the perspective of other poorly soluble low-toxicity particles.

Methods: A database of 177 articles was gathered from different sources.

Applying Existing Particle Paradigms to Inhaled Microplastic Particles.

Ambient particulate pollution originating from plastic contaminates air, including indoor and urban environments. The recent discovery of ambient microplastic (MP) particles of a size capable of depositing in the thoracic region of the airway, if inhaled, has raised concern for public exposure and health impacts following lessons learned from other particle domains. Current microplastic exposure estimates are relatively low compared to total ambient particulate matter, but optimal analytical techniques and therefore data for risk and health impact assessments are lacking.

Inflammation as a Key Outcome Pathway in Particle Induced Effects in the Lung.

Inflammation is considered a key event in the pathology of many chronic diseases, including pulmonary and systemic particle induced effects. In addition, inflammation is now considered as the key response in standard setting for poorly-soluble low toxicity (PSLT) particles and also the critical endpoint to screen for in OECD based sub-chronic animal inhalation testing protocols. During Particles & Health 2021, an afternoon session was dedicated to the subject and a brief summary of the most important messages are summarized in this paper.

Bimodal Interventional Instrument Markers for Magnetic Particle Imaging and Magnetic Resonance Imaging-A Proof-of-Concept Study.

The purpose of this work was to develop instrument markers that are visible in both magnetic particle imaging (MPI) and magnetic resonance imaging (MRI). The instrument markers were based on two different magnetic nanoparticle types (synthesized in-house KLB and commercial Bayoxide E8706). Coatings containing one of both particle types were fabricated and measured with a magnetic particle spectrometer (MPS) to estimate their MPI performance.

The parallels between particle induced lung overload and particle induced periprosthetic osteolysis (PPOL).

When particles deposit for instance in the lung after inhalation or in the hip joint after local release from a hip implant material they can initiate a defense response. Even though these particles originate from inert materials such as polyethylene (PE) or titanium, they may cause harm when reaching high local doses and overwhelming local defense mechanisms. This paper describes the parallels between adverse outcome pathways (AOP) and particle properties in lung overload and periprosthetic osteolysis (PPOL).

Optimised passive marker device visibility and automatic marker detection for 3-T MRI-guided endovascular interventions: a pulsatile flow phantom study.

Background: Passive paramagnetic markers on magnetic resonance imaging (MRI)-compatible endovascular devices induce susceptibility artifacts, enabling MRI-visibility and real-time MRI-guidance. Optimised visibility is crucial for automatic detection and device tracking but depends on MRI technical parameters and marker characteristics. We assessed marker visibility and automatic detection robustness for varying MRI parameters and marker characteristics in a pulsatile flow phantom.

Comment on Saber et al. (2019), "Commentary: the chronic inhalation study in rats for assessing lung cancer risk may be better than its reputation".

In their Commentary Saber et al. (Part Fibre Toxicol 16: 44, 2019) argue that chronic inhalation studies in rats can be used for assessing the lung cancer risk of insoluble nanomaterials. The authors make several significant errors in their interpretation and representation of the underlying science.

Expert workshop on the hazards and risks of poorly soluble low toxicity particles.

'Lung particle overload' refers to the impaired lung particle clearance and increased particle retention occurring with high lung doses of poorly soluble low toxicity (PSLT) particles. In rats, lung particle overload is associated with inflammation, epithelial hyperplasia, and, in extreme cases, lung cancer. While the human relevance of rat lung tumors occurring under overload has been questioned, recent regulatory decisions have considered these outcomes evidence of possible human hazard.

The hazards and risks of inhaled poorly soluble particles - where do we stand after 30 years of research?

Background: In 2006, titanium dioxide and carbon black were classified by IARC as "possibly carcinogenic to humans" and in 2017 the European Chemicals Agency's (ECHA) Committee for Risk Assessment concluded titanium dioxide meets the criteria to be classified as suspected of causing cancer (category 2, through the inhalation route). These classifications were based primarily on the occurrence of lung cancer in rats exposed chronically to high concentrations of these materials, as no such responses have been observed in other animal species similarly exposed. After the EU classification of titanium dioxide, it was suggested that Poorly Soluble particles of Low Toxicity (PSLTs) can be evaluated as a group.

Labeling of Collagen Type I Templates with a Naturally Derived Contrast Agent for Noninvasive MR Imaging in Soft Tissue Engineering.

In vivo monitoring of tissue-engineered constructs is important to assess their integrity, remodeling, and degradation. However, this is challenging when the contrast with neighboring tissues is low, necessitating labeling with contrast agents (CAs), but current CAs have limitations (i.e.

An updated review of the genotoxicity of respirable crystalline silica.

Human exposure to (certain forms of) crystalline silica (CS) potentially results in adverse effects on human health. Since 1997 IARC has classified CS as a Group 1 carcinogen [1], which was confirmed in a later review in 2012 [2]. The genotoxic potential and mode of genotoxic action of CS was not conclusive in either of the IARC reviews, although a proposal for mode of actions was made in an extensive review of the genotoxicity of CS by Borm, Tran and Donaldson in 2011 [3].

Magnetic Particle Imaging: A Resovist Based Marking Technology for Guide Wires and Catheters for Vascular Interventions.

Magnetic particle imaging (MPI) is able to provide high temporal and good spatial resolution, high signal to noise ratio and sensitivity. Furthermore, it is a truly quantitative method as its signal strength is proportional to the concentration of its tracer, superparamagnetic iron oxide nanoparticles (SPIOs), over a wide range practically relevant concentrations. Thus, MPI is proposed as a promising future method for guidance of vascular interventions.

Silica-induced NLRP3 inflammasome activation in vitro and in rat lungs.

Rationale: Mineral particles in the lung cause inflammation and silicosis. In myeloid and bronchial epithelial cells the inflammasome plays a role in responses to crystalline silica. Thioredoxin (TRX) and its inhibitory protein TRX-interacting protein link oxidative stress with inflammasome activation.

Comparative performance of a panel of commercially available antimicrobial nanocoatings in Europe.

Background: Bacterial resistance against the classic antibiotics is posing an increasing challenge for the prevention and treatment of infections in health care environments. The introduction of antimicrobial nanocoatings with active ingredients provides alternative measures for active killing of microorganisms, through a preventive hygiene approach.

Purpose: The purpose of this study was to investigate the antimicrobial activity of a panel of antimicrobial coatings available on the European market.

A theranostic agent to enhance osteogenic and magnetic resonance imaging properties of calcium phosphate cements.

With biomimetic biomaterials, like calcium phosphate cements (CPCs), non-invasive assessment of tissue regeneration is challenging. This study describes a theranostic agent (TA) to simultaneously enhance both imaging and osteogenic properties of such a bone substitute material. For this purpose, mesoporous silica beads were produced containing an iron oxide core to enhance bone magnetic resonance (MR) contrast.

Dual contrast agent for computed tomography and magnetic resonance hard tissue imaging.

Calcium phosphate cements (CPCs) are commonly used bone substitute materials, which closely resemble the composition of the mineral phase of bone. However, this high similarity to natural bone also results in difficult discrimination from the bone tissue by common imaging modalities, that is, plain X-ray radiography and three-dimensional computed tomography (CT). In addition, new imaging techniques introduced for bone tissue visualization, like magnetic resonance imaging (MRI), face a similar problem.

A planar conformation and the hydroxyl groups in the B and C rings play a pivotal role in the antioxidant capacity of quercetin and quercetin derivatives.

The polyphenol quercetin (Q) that has a high antioxidant capacity is a lead compound in the design of antioxidants. We investigated the possibility of modifying quercetin while retaining its antioxidant capacity as much as possible. To this end, the antioxidant capacities of Q, rutin, monohydroxyethyl rutinoside (monoHER) and a series of synthesized methylated Q derivatives were determined.

The carcinogenic action of crystalline silica: a review of the evidence supporting secondary inflammation-driven genotoxicity as a principal mechanism.

In 1987 the International Agency for Research on Cancer (IARC) classified crystalline silica (CS) as a probable carcinogen and in 1997 reclassified it as a Group 1 carcinogen, i.e., that there was sufficient evidence for carcinogenicity in experimental animals and sufficient evidence for carcinogenicity in humans.

Cement-related particles interact with proinflammatory IL-8 chemokine from human primary oropharyngeal mucosa cells and human epithelial lung cancer cell line A549.

Epidemiological studies have shown that respirable exposure to emitted cement particulate matter is associated with adverse health risk for human. The underlying mechanisms, however, are poorly understood. To examine the effect of cement, nine blinded cement-related particulates (<10 μm) were assessed with regard to their induction of the proinflammatory cytokines IL-6 and IL-8 in human primary epithelial cells (pEC) from oropharyngeal mucosa as well as from nonsmall-cell lung carcinoma (non-SCLC) cells A549.

Multifunctional Nanocarriers for diagnostics, drug delivery and targeted treatment across blood-brain barrier: perspectives on tracking and neuroimaging.

Nanotechnology has brought a variety of new possibilities into biological discovery and clinical practice. In particular, nano-scaled carriers have revolutionalized drug delivery, allowing for therapeutic agents to be selectively targeted on an organ, tissue and cell specific level, also minimizing exposure of healthy tissue to drugs. In this review we discuss and analyze three issues, which are considered to be at the core of nano-scaled drug delivery systems, namely functionalization of nanocarriers, delivery to target organs and in vivo imaging.