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.

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.

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].

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.

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.

Elemental composition and oxidative properties of PM(2.5) in Estonia in relation to origin of air masses - results from the ECRHS II in Tartu.

Fine particulate matter (PM(2.5)) was sampled at an urban background site in Tartu, Estonia over one-year period during the ECRHS II study. The elemental composition of 71 PM(2.

Associations of urban air particulate composition with inflammatory and cytotoxic responses in RAW 246.7 cell line.

Epidemiological studies show heterogeneities in the particulate pollution-related exposure-effect relationships among cardiorespiratory patients, but the connection to chemical composition and toxic properties of the inhaled particles is largely unknown. To identify the chemical constituents and sources responsible for the diverse inflammatory and cytotoxic effects of urban air, fine (PM(2.5-0.

Particle induced toxicity in relation to transition metal and polycyclic aromatic hydrocarbon contents.

Exposure to ambient particulate matter (PM) is statistically significantly associated with morbidity and mortality. The objectives of this study were (a) to investigate in vivo pulmonary and systemic cytotoxicity and inflammatory activity in compromised animals exposed to PM and (b) to investigate the relationships of the outcomes to the chemical compositions of particular polycyclic aromatic hydrocarbons (PAH) and transition metals in the PM. The PM samples were collected in European cities representing contrasting situations.

MR-compatible polyetheretherketone-based guide wire assisting MR-guided stenting of iliac and supraaortic arteries in swine: feasibility study.

The purpose of this study was to demonstrate first magnetic resonance (MR)-guided stenting of iliac and supraaortic arteries using a polyetheretherketone-based (PEEK) MR-compatible guide wire. In vitro and animal experiments were performed in a short magnet wide-bore scanner (1.5 Tesla, Espree, Siemens Healthcare, Erlangen, Germany).

First magnetic resonance imaging-guided aortic stenting and cava filter placement using a polyetheretherketone-based magnetic resonance imaging-compatible guidewire in swine: proof of concept.

The purpose of this study was to demonstrate feasibility of percutaneous transluminal aortic stenting and cava filter placement under magnetic resonance imaging (MRI) guidance exclusively using a polyetheretherketone (PEEK)-based MRI-compatible guidewire. Percutaneous transluminal aortic stenting and cava filter placement were performed in 3 domestic swine. Procedures were performed under MRI-guidance in an open-bore 1.

Drug delivery and nanoparticles:applications and hazards.

The use of nanotechnology in medicine and more specifically drug delivery is set to spread rapidly. Currently many substances are under investigation for drug delivery and more specifically for cancer therapy. Interestingly pharmaceutical sciences are using nanoparticles to reduce toxicity and side effects of drugs and up to recently did not realize that carrier systems themselves may impose risks to the patient.

Impact of the FcgammaII-receptor on quartz uptake and inflammatory response by alveolar macrophages.

The inflammatory response following particle inhalation is described as a key event in the development of lung diseases, e.g., fibrosis and cancer.

Curcumin protects against cytotoxic and inflammatory effects of quartz particles but causes oxidative DNA damage in a rat lung epithelial cell line.

Chronic inhalation of high concentrations of respirable quartz particles has been implicated in various lung diseases including lung fibrosis and cancer. Generation of reactive oxygen species (ROS) and oxidative stress is considered a major mechanism of quartz toxicity. Curcumin, a yellow pigment from Curcuma longa, has been considered as nutraceutical because of its strong anti-inflammatory, antitumour and antioxidant properties.

Surface-dependent quartz uptake by macrophages: potential role in pulmonary inflammation and lung clearance.

Inhalation of quartz particles is associated with a variety of adverse lung effects. Since particle surface is considered to be crucial for particle pathogenicity, we investigated the influence of quartz surface properties on lung burden, inflammation (bronchoalveolar lavage cells), and cytotoxicity (protein, lactate dehydrogenase, beta-glucuronidase) 90 days after a single intratracheal instillation of 2 mg DQ12 into rats. The role of particle surface characteristics was investigated by comparative investigation of native versus surface-modified quartz, using polyvinylpyridine N-oxide (PVNO) or aluminum lactate (AL) coating.

Nanoparticles in drug delivery and environmental exposure: same size, same risks?

Engineered nanoparticles are an important tool for future nanomedicines to deliver and target drugs or bring imaging agents to the targets where they are required. Since the original application of liposomes in the 1970s, a wealth of carrier and imaging systems has been developed, including magnetoliposomes, dendrimers, fullerenes and polymer carriers. However, to make use of this potential, toxicological issues must be addressed, in particular because of findings on combustion-derived nanoparticles in environmentally exposed populations, which show effects in those with respiratory or cardiovascular diseases.

Endocytosis, oxidative stress and IL-8 expression in human lung epithelial cells upon treatment with fine and ultrafine TiO2: role of the specific surface area and of surface methylation of the particles.

Inhaled ultrafine particles show considerably stronger pulmonary inflammatory effects when tested at equal mass dose with their fine counterparts. However, the responsible mechanisms are not yet fully understood. We investigated the role of particle size and surface chemistry in initiating pro-inflammatory effects in vitro in A549 human lung epithelial cells on treatment with different model TiO(2) particles.

Testing strategies to establish the safety of nanomaterials: conclusions of an ECETOC workshop.

The European Centre for Ecotoxicology and Toxicology of Chemicals (ECETOC) convened a workshop in Barcelona, Spain, in November 2005 to develop testing strategies to establish the safety of nanomaterials. It brought together about 70 scientific and clinical experts from industry, academia, government agencies, research institutes, and nongovernmental organizations. The primary questions to be addressed were the following: What can we do today, and what do we need tomorrow? The three major themes of the workshop were: (1) the need for enhanced efforts in nanomaterial characterization; (2) methodologies for assessments of airborne and internal exposures to nanomaterials; and (3) evaluation of the hazard potential--primarily focusing on pulmonary or dermal routes of exposures.

Actin plays a crucial role in the phagocytosis and biological response to respirable quartz particles in macrophages.

The uptake of respirable quartz particles by alveolar macrophages (AM) is believed to cause an inflammatory response, which is discussed as a crucial step in quartz pathogenicity. However, little is known about the mechanism and the relevance of particle uptake. Therefore, the aim of this study was to analyze the role of the actin cytoskeleton in quartz particle uptake, reactive oxygen species generation (ROS) and tumour necrosis factor alpha (TNF-alpha) release.