Assessing the toxicity of traffic-derived air pollution using a primary human air-liquid interface airway in vitro model.

Traffic-derived air pollution (TDAP) frequently exceeds the 2021 World Health Organization air quality guideline levels and is linked to respiratory diseases through molecular mechanisms such as oxidative stress and inflammation. To determine these mechanisms without relying on animal models and inter-species extrapolation, physiologically relevant human in vitro models are promising tools. We sought to investigate the oxidative stress and inflammatory responses to TDAP in a co-culture model of the human lung.

Kidney morphological changes associated with early-life carbonaceous ultrafine particle exposure: A pathomics approach.

Background: Fine particulate matter (<2.5 μm, PM), and its subcomponent ultrafine carbonaceous particles (UFP), have been shown to cause adverse health effects, including respiratory and cardiovascular disease, and decline in kidney function. Previous research demonstrated the presence of these particles in the kidney, yet potential effects on kidney tissue remain elusive.

Application of in vitro pulmonary models for hazard screening of silica particles.

There is an increasing need for new approach methodologies (NAMs) for safety assessment of nanomaterials (NMs) in order to keep pace with innovation. In vitro assays are useful tools during pre-market hazard screening approaches of NMs to prioritize safe(r) candidate NMs and reduce the amount of regulatory testing required. For pre-regulatory hazard screening applications, it is crucial that in vitro assays have the capacity to distinguish between NMs based on their hazard potency and have the ability to provide accurate hazard rankings.

Hazard screening of colloidal silica nanomaterials with varying degrees of silane surface functionalization: a safe-by-design case study.

Background: The Safe and Sustainable by Design (SSbD) concept facilitates the design of safer and more sustainable chemicals and materials and is a crucial approach towards reaching the goals set out in the European Green Deal. It is critical that suitable guidance is provided on how to use new approach methodologies (NAMs) to fill hazard data gaps for nanomaterials (NMs) to facilitate SSbD decisions. Here, we showcase a nano-specific in vitro SSbD case study.

Altered cytokine release of airway epithelial cells in vitro by combinations of respiratory syncytial virus, Streptococcus pneumoniae, Printex 90 and diesel exhaust particles.

Air pollution exposure has been linked to an increased severity of respiratory infections. Studying the cellular mechanisms behind a potential interaction between biological infectious agents, like viruses or bacteria, and the chemical constituent of air pollution could provide more understanding of this finding. In vitro models allow assessment of the mechanisms leading to such increased severity of respiratory infections.

Copper-enriched automotive brake wear particles perturb human alveolar cellular homeostasis.

Background: Airborne fine particulate matter with diameter < 2.5 μm (PM2.5), can reach the alveolar regions of the lungs, and is associated with over 4 million premature deaths per year worldwide.

Impact on murine neurodevelopment of early-life exposure to airborne ultrafine carbon nanoparticles.

The effects of ultrafine particle (UFP) inhalation on neurodevelopment, especially during critical windows of early life, remain largely unexplored. The specific time windows during which exposure to UFP might be the most detrimental remain poorly understood. Here, we studied early-life exposure to clean ultrafine carbonaceous particles (UFP) and neurodevelopment and central nervous system function in offspring.

Comparison of the neurotoxic potency of different ultrafine particle fractions from diesel engine exhaust following direct and simulated inhalation exposure.

Exposure to traffic-related air pollution and ultrafine particles (<100 nm; UFP) is linked with neurodegeneration. However, the impact of the aromatic content in fuels and the contribution of different fractions of UFP, i.e.

Expanded PAH analysis of household air pollution in a rural region of China with high lung cancer incidence.

The domestic combustion of locally sourced smoky (bituminous) coal in Xuanwei and Fuyuan counties, China, is responsible for some of the highest lung cancer rates in the world. Recent research has pointed to methylated PAHs (mPAHs), particularly 5-methylchrysene (5MC), within coal combustion products as a driving factor. Here we describe measurements of mPAHs in Xuanwei and Fuyuan derived from controlled burnings (i.

Biodistribution of cerium dioxide and titanium dioxide nanomaterials in rats after single and repeated inhalation exposures.

Background: Physiologically based kinetic models facilitate the safety assessment of inhaled engineered nanomaterials (ENMs). To develop these models, high quality datasets on well-characterized ENMs are needed. However, there are at present, several data gaps in the systemic availability of poorly soluble particles after inhalation.

Roadmap towards safe and sustainable advanced and innovative materials. (Outlook for 2024-2030).

The adoption of innovative advanced materials holds vast potential, contingent upon addressing safety and sustainability concerns. The European Commission advocates the integration of Safe and Sustainable by Design (SSbD) principles early in the innovation process to streamline market introduction and mitigate costs. Within this framework, encompassing ecological, social, and economic factors is paramount.

Improving the dichloro-dihydro-fluorescein (DCFH) assay for the assessment of intracellular reactive oxygen species formation by nanomaterials.

To facilitate Safe and Sustainable by Design (SSbD) strategies during the development of nanomaterials (NMs), quick and easy in vitro assays to test for hazard potential at an early stage of NM development are essential. The formation of reactive oxygen species (ROS) and the induction of oxidative stress are considered important mechanisms that can lead to NM toxicity. In vitro assays measuring oxidative stress are therefore commonly included in NM hazard assessment strategies.

Micro- and nanoplastics concepts for particle and fibre toxicologists.

Micro- and nanoplastic particles (MNP) are omnipresent as either pollution or intentionally used in consumer products, released from packaging or even food. There is an exponential increase in the production of plastics. With the realization of bioaccumulation in humans, toxicity research is quickly expanding.

First-in-human controlled inhalation of thin graphene oxide nanosheets to study acute cardiorespiratory responses.

Graphene oxide nanomaterials are being developed for wide-ranging applications but are associated with potential safety concerns for human health. We conducted a double-blind randomized controlled study to determine how the inhalation of graphene oxide nanosheets affects acute pulmonary and cardiovascular function. Small and ultrasmall graphene oxide nanosheets at a concentration of 200 μg m or filtered air were inhaled for 2 h by 14 young healthy volunteers in repeated visits.

In vitro neurotoxicity of particles from diesel and biodiesel fueled engines following direct and simulated inhalation exposure.

Combustion-derived particulate matter (PM) is a major source of air pollution. Efforts to reduce diesel engine emission include the application of biodiesel. However, while urban PM exposure has been linked to adverse brain effects, little is known about the direct effects of PM from regular fossil diesel (PMDEP) and biodiesel (PMBIO) on neuronal function.

Airway contraction and cytokine release in isolated rat lungs induced by wear particles from the road and tire interface and road vehicle brakes.

The dominant road traffic particle sources are wear particles from the road and tire interface, and from vehicle brake pads. The aim of this work was to investigate the effect of road and brake wear particles on pulmonary function and biomarkers in isolated perfused rat lungs. Particles were sampled from the studded tire wear of three road pavements containing different rock materials in a road simulator; and from the wear of two brake pad materials using a pin-on-disk machine.

Placental-fetal distribution of carbon particles in a pregnant rabbit model after repeated exposure to diluted diesel engine exhaust.

Background: Airborne pollution particles have been shown to translocate from the mother's lung to the fetal circulation, but their distribution and internal placental-fetal tissue load remain poorly explored. Here, we investigated the placental-fetal load and distribution of diesel engine exhaust particles during gestation under controlled exposure conditions using a pregnant rabbit model. Pregnant dams were exposed by nose-only inhalation to either clean air (controls) or diluted and filtered diesel engine exhaust (1 mg/m) for 2 h/day, 5 days/week, from gestational day (GD) 3 to GD27.

In vitro neurotoxicity screening of engine oil- and hydraulic fluid-derived aircraft cabin bleed-air contamination.

In most airplanes, cabin air is extracted from the turbine compressors, so-called bleed air. Bleed air can become contaminated by leakage of engine oil or hydraulic fluid and possible neurotoxic constituents, like triphenyl phosphate (TPhP) and tributyl phosphate (TBP). The aim of this study was to characterize the neurotoxic hazard of TBP and TPhP, and to compare this with the possible hazard of fumes originating from engine oils and hydraulic fluids in vitro.

The State of the Art and Challenges of In Vitro Methods for Human Hazard Assessment of Nanomaterials in the Context of Safe-by-Design.

The Safe-by-Design (SbD) concept aims to facilitate the development of safer materials/products, safer production, and safer use and end-of-life by performing timely SbD interventions to reduce hazard, exposure, or both. Early hazard screening is a crucial first step in this process. In this review, for the first time, commonly used in vitro assays are evaluated for their suitability for SbD hazard testing of nanomaterials (NMs).

Establishing relationships between particle-induced in vitro and in vivo inflammation endpoints to better extrapolate between in vitro markers and in vivo fibrosis.

Background: Toxicity assessment for regulatory purposes is starting to move away from traditional in vivo methods and towards new approach methodologies (NAM) such as high-throughput in vitro models and computational tools. For materials with limited hazard information, utilising quantitative Adverse Outcome Pathways (AOPs) in a testing strategy involving NAM can produce information relevant for risk assessment. The aim of this work was to determine the feasibility of linking in vitro endpoints to in vivo events, and moreover to key events associated with the onset of a chosen adverse outcome to aid in the development of NAM testing strategies.

An inter-laboratory effort to harmonize the cell-delivered in vitro dose of aerosolized materials.

Air-liquid interface (ALI) lung cell models cultured on permeable transwell inserts are increasingly used for respiratory hazard assessment requiring controlled aerosolization and deposition of any material on ALI cells. The approach presented herein aimed to assess the transwell insert-delivered dose of aerosolized materials using the VITROCELL® Cloud12 system, a commercially available aerosol-cell exposure system. An inter-laboratory comparison study was conducted with seven European partners having different levels of experience with the VITROCELL® Cloud12.

Neuromodulatory and neurotoxic effects of e-cigarette vapor using a realistic exposure method.

The most direct effects of inhaled harmful constituents are the effects on the airways. However, inhaled compounds can be rapidly absorbed and subsequently result in systemic effects. For example, e-cigarette vapor has been shown to evoke local effects in the lung, although little is known about subsequent effects in secondary target organs such as the brain.