Pharmacology, Toxicology and Environmental Health Commons^™

Numerical Simulations Of In Vitro Nanoparticle Toxicity – The Case Of Poly(Amido Amine) Dendrimers., Marcus Maher, Pratap Naha, Sourav Prasanna Mukherjee, Hugh Byrne

Articles

A phenomenological rate equation model is constructed to numerically simulate nanoparticle uptake and subsequent cellular response. Polyamidoamine dendrimers (generations 4-6) are modelled and the temporal evolution of the intracellular cascade of; increased levels of reactive oxygen species, intracellular antioxidant species, caspase activation, mitochondrial membrane potential decay, tumour necrosis factor and interleukin generation is simulated, based on experimental observations.

The dose and generation dependence of several of these response factors are seen to well represent experimental observations at a range of time points. The model indicates that variations between responses of different cell-lines, including murine macrophages, human keratinocytes and colon cells, …

Size Dependent Translocation And Fetal Accumulation Of Gold Nanoparticles From Maternal Blood In The Rat., Manuela Semmler-Behnke, Jens Lipka, Alexander Wenk, Martin Schäffler, Furong Tian, Günter Schmid, Günter Oberdörster, Wolfgang G. Kreyling

Articles

Background

There is evidence that nanoparticles (NP) cross epithelial and endothelial body barriers. We hypothesized that gold (Au) NP, once in the blood circulation of pregnant rats, will cross the placental barrier during pregnancy size-dependently and accumulate in the fetal organism by 1. transcellular transport across the hemochorial placenta, 2. transcellular transport across amniotic membranes 3. transport through ~20 nm wide transtrophoblastic channels in a size dependent manner. The three AuNP sizes used to test this hypothesis are either well below, or of similar size or well above the diameters of the transtrophoblastic channels.

Methods

We intravenously injected monodisperse, negatively …

The Association Of Cold Weather And All-Cause And Cause-Specific Mortality In The Island Of Ireland Between 1984 And 2007, Ariana Zeka, Stephen Browne, Helen Mcavoy, Patrick Goodman

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Background: This study aimed to assess the relationship between cold temperature and daily mortality in the Republic of Ireland (ROI) and Northern Ireland (NI), and to explore any differences in the population responses between the two jurisdictions. Methods: A time-stratified case-crossover approach was used to examine this relationship in two adult national populations, between 1984 and 2007. Daily mortality risk was examined in association with exposure to daily maximum temperatures on the same day and up to 6 weeks preceding death, during the winter (December-February) and an extended cold period (October-March), using distributed lag models. Model stratification by age and …

Epoxy Resin Monomers With Reduced Skin Sensitizing Potency, Niamh F. O'Boyle, Ida B. Niklasson, Ali R. Tehrani-Bagda, Tamara Delaine, Krister Holmberg, Kristina Luthman, Ann-Therese Karlberg

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Epoxy resin monomers, including diglycidyl ethers of bisphenol A and F (DGEBA and DGEBF), are extensively used as building blocks for thermosetting polymers. However, they are known to cause widespread contact allergy. This research describes a number of alternative epoxy resin monomers, designed with the aim of reducing the skin sensitizing potency whilst maintaining the ability to form thermosetting polymers. The compounds were designed, synthesized, assessed for skin sensitizing potency using the in vivo murine local lymph node assay, and tested for technical applicability using thermogravimetric analysis and differential scanning calorimetry. All the novel epoxy resin monomers had decreased skin …

Β-Lactam Estrogen Receptor Antagonists And A Dual-Targeting Estrogen Receptor/Tubulin Ligand, Niamh O'Boyle, Jade K. Pollock, Miriam Carr, Andrew Js Knox, Seema M. Nathwani, Shu Wang, Laura Caboni, Daniela M. Zisterer, Mary Meegan

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Twelve novel β-lactams were synthesised and their antiproliferative effects and binding affinity for the predominant isoforms of the estrogen receptor (ER), ERα and ERβ, were determined. β-Lactams 23 and 26 had the strongest binding affinities for ERα (IC₅₀ values: 40 and 8 nM respectively) and ERβ (IC₅₀ values: 19 and 15 nM). β-Lactam 26 was the most potent in antiproliferative assays using MCF-7 breast cancer cells, and further biochemical analysis showed that it caused accumulation of cells in G₂/M phase (mitotic blockade) and depolymerisation of tubulin in MCF-7 cells. Compound 26 also induced apoptosis and downregulation …

Concern-Driven Integrated Toxicity Testing Strategies For Nanomaterials - Report Of The Nanosafety Cluster Working Group 10, Hugh Byrne, Agnes G. Oomen, Peter M.J. Bos, Teresa F. Fernandes, Kerstin Hund-Rinke, Diana Boraschi, Karin Aschberger, Stefania Gottardo, Frank Von Der Kammer, Dana Kühnel, Danail Hristozov, Antonio Marcomini, Lucia Migliore

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Bringing together topic-related European Union-(EU)-funded projects, the so-called “NanoSafety Cluster” aims at identifying key areas for further research on risk assessment procedures for nanomaterials (NM). The outcome of NanoSafety Cluster Working Group 10, this commentary presents a vision for concern-driven integrated approaches for the (eco-)toxicological testing and assessment (IATA) of NM. Such approaches should start out by determining concerns, i.e. specific information needs for a given NM based on realistic exposure scenarios. Recognized concerns can be addressed in a set of tiers using standardized protocols for NM preparation and testing. Tier 1 includes determining physico-chemical properties, non-testing (e.g. structure …