COVID-19 through Adverse Outcome Pathways: Building networks to better understand the disease - 3rd CIAO AOP Design Workshop

ALTEX - Alternatives to Animal ExperimentationCopyright © 2022 the author(s). On April 28-29, 2021, 50 scientists from different fields of expertise met for the 3rd online CIAO workshop. The CIAO project “Modelling the Pathogenesis of COVID-19 using the Adverse Outcome Pathway (AOP) framework” aims at building a holistic assembly of the available scientific knowledge on COVID-19 using the AOP framework. An individual AOP depicts the disease progression from the initial contact with the SARS-CoV-2 virus through biological key events (KE) toward an adverse outcome such as respiratory distress, anosmia or multiorgan failure. Assembling the individual AOPs into a network highlights shared KEs as central biological nodes involved in multiple outcomes observed in COVID-19 patients. During the workshop, the KEs and AOPs established so far by the CIAO members were presented and posi­tioned on a timeline of the disease course. Modulating factors influencing the progression and severity of the disease were also addressed as well as factors beyond purely biological phenomena. CIAO relies on an interdisciplinary crowd­sourcing effort, therefore, approaches to expand the CIAO network by widening the crowd and reaching stakeholders were also discussed. To conclude the workshop, it was decided that the AOPs/KEs will be further consolidated, inte­grating virus variants and long COVID when relevant, while an outreach campaign will be launched to broaden the CIAO scientific crowd.The CIAO project is steered by the Joint Research Centre of the European Commission (EC-JRC), the Humane Society International (HSI), and the Physicians Committee for Responsible Medicine (PCRM). For Jorid Birkelund Sørli, the research is supported by FIKA, Focused Research Effort on Chemicals in the Working Environment from the Danish Government. For Daniel Jacobson, this work was supported by the Laboratory Directed Research and Development Program of Oak Ridge National Laboratory, managed by UT-Battelle, LLC for the US Department of Energy (LOIS:10074) and the National Institutes of Health 3RF1AG053303-01S2

In vitro prediction of clinical signs of respiratory toxicity in rats following inhalation exposure

To date there are no OECD validated alternative approaches to study toxicity following inhalation exposure to airborne chemicals. The available OECD test guidelines for acute inhalation toxicity aim to estimate a value of the lethal air concentration of the test chemical leading to the death of 50% of the exposed animals (LC(50)), to satisfy hazard classification and labelling requirements. This paper explores the view that alternative approaches must compare to outcomes of existing guideline methods to become accepted and implemented in a regulatory context. This case study describes the initiatives taken to validate the lung surfactant bioassay, an in vitro cell-free method, and discusses the challenges faced. While the lung surfactant bioassay could not predict the GHS classification for acute inhalation toxicity of 26 chemicals, the assay successfully predicted the clinical signs of respiratory toxicity observed during or shortly after exposure in vivo as reported in registration dossiers. The lung surfactant bioassay is a promising alternative approach to assess the potential of chemicals to cause changes to respiration remaining after exposure (indicating decreased lung function), and can be combined with other test methods in an integrated approach to testing and assessment of inhaled substances

Pulmonary injury associated with spray of a water-based nano-sized waterproofing product: a case study

Abstract Background In most reported cases of lung trauma with water proofing products, volatile organic compounds (VOC) have a prominent role. Here we report on a case involving ten workers exposed to a sprayed product containing nanoparticles in a water solution with only a few percent VOC. Case presentation Ten workers suffered from respiratory symptoms following spray impregnation of hardwood furniture using a waterproofing product that contained positively charged fluorinated acrylate copolymer solid cores with a median diameter of 70 nm (1.3 w%) in aqueous suspension with 3.3 w% VOC and 0.3 w% quaternary ammonium. The worker who applied one liter of the product in a wood workshop, using an air mix spray gun, did not report any health complaints. Another worker, who entered the workshop 3 h later and had rolled and smoked two cigarettes, was hospitalized with severe chemical pneumonitis. A chest X-ray (CXR) showed bilateral infiltrative impairment in the lower lobe regions. On the next day a second CXR showed increased patchiness marking in all fields. A high-resolution Computer Tomography (CT)-scan demonstrated extensive bilateral areas of ground-glass opacities predominantly in the lower regions of the upper lobes, the right middle lobe and the apical regions of the lower lobes, compatible with severe chemical pneumonitis. On the following morning, nine workers in an adjacent workplace in the same building, experienced dry cough, chest tightness and substernal pain upon physical exercise. Reconstruction of the spray application in a climate chamber confirmed trimethyl silanol, glycol ethers and fluoroalkenes in the gas phase. Immediately after the spray application, aerosols were observed at a maximum concentration of 6.3 × 104 cm−3. Mass concentrations were 0.095 and 10 mg/m3 in the size ranges 5.6-560 nm and 0.22-30 μm, respectively, decreasing to less than 10 μg/m3 in both size ranges after 15 h. Conclusion The hospitalized worker had smoked cigarettes contaminated with fluoropolymers which is a plausible explanation for the lung trauma. Respiratory symptoms in the nine workers may be caused by inhalation of particles that became airborne by resuspension from surfaces when workers entered the adjacent workplace the next day. A contribution from VOC appears less likely because measurements and modelling showed that concentrations in the mg/m3 range could have occurred only if the building was assumed to be completely airtight

'Endemic to the species':Ordering the 'other' via organised crime

The United States has been the prime mover in the establishment of both the concept of organised crime and the use of the concept in its attempt to establish global hegemony, in which law enforcement became a little more than a front for a government-backed central casting agency, stereotyping both heroes and villains. This article offers an account of how the ?Other? has been used as prism for the construction of organised crime primarily in the United States and how this construction, as a franchise, has been exported on the international level and on heterogeneous criminal landscapes