Health implications of nanoparticles
ABSTRACT Nanoparticles are increasingly used in a wide range of applications in science, technology and medicine. Since they are produced for specific purposes which cannot be met by larger particles and bulk material they are likely to be highly reactive, in particular, with biological systems. On the other hand a large body of know-how in environmental sciences is available from toxicological effects of ultrafine particles (smaller than 100nm in size) after inhalation. Since nanoparticles feature similar reactivity as ultrafine particles a sustainable development of new emerging nanoparticles is required. This paper gives a brief review on the dosimetry of nanoparticles, including deposition in the various regions of the respiratory tract and systemic translocation and uptake in secondary target organs, epidemiologic associations with health effects and toxicology of inhaled nanoparticles. General principles and current paradigms to explain for the specific behaviour of nanoparticles in toxicology are discussed. With that respect we consider nanoparticles to be in the range from 1 to 2nm (clusters of atoms/molecules) to particles that are smaller than 100nm at least in one dimension. Since the evidence for health risks of ultrafine and nanoparticles after inhalation has been increasing over the last decade, the paper attempts to extrapolate these findings and principles observed in particle inhalation toxicology into recommendations for an integrated concept of risk assessment of nanoparticles for a broad range of use in science, technology and medicine.
- SourceAvailable from: jimmunol.org[show abstract] [hide abstract]
ABSTRACT: Inhaled diesel exhaust particles (DEP) exert proinflammatory effects in the respiratory tract. This effect is related to the particle content of redox cycling chemicals and is involved in the adjuvant effects of DEP in atopic sensitization. We demonstrate that organic chemicals extracted from DEP induce oxidative stress in normal and transformed bronchial epithelial cells, leading to the expression of heme oxygenase 1, activation of the c-Jun N-terminal kinase cascade, IL-8 production, as well as induction of cytotoxicity. Among these effects, heme oxygenase 1 expression is the most sensitive marker for oxidative stress, while c-Jun N-terminal kinase activation and induction of apoptosis-necrosis require incremental amounts of the organic chemicals and increased levels of oxidative stress. While a macrophage cell line (THP-1) responded in similar fashion, epithelial cells produced more superoxide radicals and were more susceptible to cytotoxic effects than macrophages. Cytotoxicity is the result of mitochondrial damage, which manifests as ultramicroscopic changes in organelle morphology, a decrease in the mitochondrial membrane potential, superoxide production, and ATP depletion. Epithelial cells also differ from macrophages in not being protected by a thiol antioxidant, N-acetylcysteine, which effectively protects macrophages against cytotoxic DEP chemicals. These findings show that epithelial cells exhibit a hierarchical oxidative stress response that differs from that of macrophages by more rapid transition from cytoprotective to cytotoxic responses. Moreover, epithelial cells are not able to convert N-acetylcysteine to cytoprotective glutathione.The Journal of Immunology 11/2002; 169(8):4531-41. · 5.52 Impact Factor
- [show abstract] [hide abstract]
ABSTRACT: This paper examines the presence and characteristics of endocytosis by oesophageal epithelial cells. Biopsy specimens from normal and inflamed oesophagus were incubated in organ culture with fluorescent microspheres (0.1 and 0.01 microns diameter). These markers were taken into early endosomes and the lysosomes of both the smaller differentiating prickle cells and the larger mature squamous cells. Confocal and electron microscopy showed that markers passed to the early endosomes and the lysosomes by endocytosis. The process was energy dependent. Larger, 1 micron microspheres adhered to the epithelial cells but were not phagocytosed. Disaggregated cells were analysed by flow cytometry. Microspheres were endocytosed in proportion to the concentration in the culture medium in a dose dependent manner. Cells from inflamed oesophagus were significantly smaller (p = 0.013) and took up significantly more microspheres than cells from normal biopsy specimens (p = 0.015). In conclusion, endocytosis occurs in oesophageal epithelial cells and is increased in inflammation.Gut 12/1995; 37(5):598-602. · 10.73 Impact Factor
- [show abstract] [hide abstract]
ABSTRACT: Fibrous materials, exemplified by asbestos, that release respirable fibres are in common use and there is considerable knowledge regarding the toxicology of these common fibres. Newer materials or those that are under development, such as synthetic organic fibres and carbon nanotubes may have a different toxicology paradigms. The existing paradigm for silicate fibres suggests that respirable fibre types vary in their ability to cause lung disease and that this can be understood on the basis of the length of the fibres and their biopersistence in the lungs. Because fibres are regulated on a fibre number basis and the hazard is understood on the basis of the number of long fibres, in fibre testing the dose should always be expressed as fibre number, not mass and the length and diameter distribution need to be known. Short-term biological tests are likely to produce false positives in the case of long non-biopersistent fibres, because whilst they may have effects in vitro, they do not persist long enough in the lungs for sufficient dose to build up and produce effects in vivo. The biopersistence of fibres is therefore a key factor that needs to be known in order to interpret short-term tests that may claim to predict fibre pathogenicity.Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 10/2004; 553(1-2):5-9. · 3.90 Impact Factor