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- Bondarenko, Olesja M., et al.
(author)
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Current challenges and coming opportunities in nanoparticle risk assessment
- 2020
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In: Colloids for Nanobiotechnology : Synthesis, Characterization and Potential Applications - Synthesis, Characterization and Potential Applications. - 1876-276X .- 1876-2778. - 9780081028285 ; 16, s. 353-371
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Book chapter (peer-reviewed)abstract
- This chapter discusses the key aspects of engineered nanomaterial (ENM) toxicity. The individual properties of ENMs affecting their toxic potential are described, with a special focus on size, shape, and surface charge and functionalization. We present empirical evidence from a range of in vitro and in vivo studies showing potential adverse effects induced via inhalation, ingestion, or skin contact with ENMs, as well as a brief overview of human studies and nanoecotoxicology. Finally, a summary of current guidelines and frameworks is provided, together with a collection of the most prominent nanosafety projects and resources available for the assessment of nanotoxicity. This literature review demonstrates that there is a need for the collection of standardized data from human studies to inform epidemiological studies. Moreover, despite the wide usage of ENMs and reported toxic potentials, there is a shortage of policies regulating the exposure and usage of ENMs to protect both the environment and human health.
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- Gallud, Audrey, et al.
(author)
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Macrophage activation status determines the internalization of mesoporous silica particles of different sizes : Exploring the role of different pattern recognition receptors
- 2017
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In: Biomaterials. - : Elsevier BV. - 0142-9612 .- 1878-5905. ; 121, s. 28-40
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Journal article (peer-reviewed)abstract
- Mesoporous silica-based particles are promising candidates for biomedical applications. Here, we address the importance of macrophage activation status for internalization of AMS6 (approx. 200 nm in diameter) versus AMS8 (approx. 2 mu m) mesoporous silica particles and the role of different phagocytosis receptors for particle uptake. To this end, FITC-conjugated silica particles were used. AMS8 were found to be non-cytotoxic both for M-CSF-stimulated (anti-inflammatory) and GM-CSF-stimulated (pro-inflammatory) macrophages, whereas AMS6 exhibited cytotoxicity towards M-CSF-stimulated, but not GMCSF-stimulated macrophages; this toxicity was, however, mitigated in the presence of serum. AMS8 triggered the secretion of pro-inflammatory cytokines in M-CSF-activated cells. Class A scavenger receptor (SR-A) expression was noted in both M-CSF and GM-CSF-stimulated macrophages, although the expression was higher in the former case, and gene silencing of SR-A resulted in a decreased uptake of AMS6 in the absence of serum. GM-CSF-stimulated macrophages expressed higher levels of the mannose receptor CD206 compared to M-CSF-stimulated cells, and uptake of AMS6, but not AMS8, was reduced following the downregulation of CD206 in GM-CSF-stimulated cells; particle uptake was also suppressed by mannan, a competitive ligand. These studies demonstrate that macrophage activation status is an important determinant of particle uptake and provide evidence for a role of different macrophage receptors for cell uptake of silica particles.
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- Krebs, Alice, et al.
(author)
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Template for the Description of Cell-Based Toxicological Test Methods to Allow Evaluation and Regulatory Use of the Data
- 2019
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In: Altex. - : ALTEX Edition. - 1868-596X .- 1868-8551. ; 36:4, s. 682-699
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Journal article (other academic/artistic)abstract
- Only few cell-based test methods are described by Organisation for Economic Co-operation and Development (OECD) test guidelines or other regulatory references (e.g., the European Pharmacopoeia). The majority of toxicity tests still falls into the category of non-guideline methods. Data from these tests may nevertheless be used to support regulatory decisions or to guide strategies to assess compounds (e.g., drugs, agrochemicals) during research and development if they fulfill basic requirements concerning their relevance, reproducibility and predictivity. Only a method description of sufficient clarity and detail allows interpretation and use of the data. To guide regulators faced with increasing amounts of data from non-guideline studies, the OECD formulated Guidance Document 211 (GD211) on method documentation for the purpose of safety assessment. As GD211 is targeted mainly at regulators, it leaves scientists less familiar with regulation uncertain as to what level of detail is required and how individual questions should be answered. Moreover, little attention was given to the description of the test system (i.e., cell culture) and the steps leading to it being established in the guidance. To address these issues, an annotated toxicity test method template (ToxTemp) was developed (i) to fulfill all requirements of GD211, (ii) to guide the user concerning the types of answers and detail of information required, (iii) to include acceptance criteria for test elements, and (iv) to define the cells sufficiently and transparently. The fully annotated ToxTemp is provided here, together with reference to a database containing exemplary descriptions of more than 20 cell-based tests.
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