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Background: There is an increasing concern about the neurotoxicity of engineered nanomaterials (NMs). To investigate the effects of subchronic oral exposures to SiO2 and CeO2 NMs on Alzheimer's disease (AD)-like pathology, 5xFAD transgenic mice and their C57BL/6J littermates were fed ad libitum for 3 or 14 weeks with control food pellets, or pellets dosed with these respective NMs at 0.1% or 1% (w/w). Behaviour effects were evaluated by X-maze, string suspension, balance beam and open field tests. Brains were analysed for plaque load, beta-amyloid peptide levels, markers of oxidative stress and neuroinflammation. Results: No marked behavioural impairments were observed in the mice exposed to SiO2 or CeO2 and neither treatment resulted in accelerated plaque formation, increased oxidative stress or inflammation. In contrast, the 5xFAD mice exposed to 1% CeO2 for 14 weeks showed significantly lower hippocampal Aβ plaque load and improved locomotor activity compared to the corresponding controls. Conclusions: The findings from the present study suggest that long-term oral exposure to SiO2 or CeO2 NMs has no neurotoxic and AD-promoting effects. The reduced plaque burden observed in the mice following dietary CeO2 exposure warrants further investigation to establish the underlying mechanism, given the easy applicability of this administration method. [ABSTRACT FROM AUTHOR]

Previous repeated inhalation exposure studies on rats with multi-walled carbon nanotubes (MWCNT, Baytubes®) suggested that their pulmonary toxicity was predominated by the morphology and density of the aggregated structure. Evidence of any disintegration of these structures in the lung did not exist. The objective of this study was to study as to which extent the formulation of pristine MWCNT as wet-dispersion changes the morphology of assemblage structures in the presence of disintegrated sub-structures. The focus was on the comparative inhalation dosimetry and kinetics of dry- and wet-dispersed Baytubes to better understand the cause of putative differences in pulmonary toxicity originating from pristine and rigorously formulated MWCNT. Rats were nose-only exposed to dry-dispersed and wet-dispersed Baytubes for 6-h at 25-30 mg/m3. Aerodynamic particle size measurements demonstrate substantial differences in the particle size of dry- (MMAD 2.6 µm) and wet-dispersed (MMAD 0.8 µm) MWCNT. Time-course changes of MWCNT retained in the lung were examined during a post-exposure period of 3 months. Lung burdens were analytically determined in digested lungs using the EC/OC total carbon method. Dosimetry was complemented by light and transmission electron microscopy (TEM) of MWCNT retained in alveolar macrophages (AM). As a result, the initially deposited pulmonary dose of MWCNT was three times higher following wet-dispersed MWCNT at essentially similar inhalation chamber concentrations. The elimination half-time of dry- and wet-dispersed MWCNT was 87 and 46 d, respectively. TEM provided evidence that wet-dispersed MWCNT were inhaled as disintegrated structures with distribution-patterns within the cytoplasm of AMs that differed appreciably from those of dry-dust exposed animals. In summary, this study shows that specialized technical processes to formulate MWCNT may have dramatic consequences on their pulmonary fate and associated toxicity. Such properties can only be revealed by the comparison of pulmonary toxicity with pulmonary (micro-)dosimetry and kinetics. [ABSTRACT FROM AUTHOR]

Specific regions in the rat larynx exhibit cellular changes in response to inhaled xenobiotics. These regions include the base of the epiglottis, ventral pouch, and medial surfaces of the vocal processes of the arytenoid cartilages. In order to collect information on the usefulness of trimming techniques, the influence of different vehicles, the impact of different application routes in toxicity studies, and differences between induced vs. spontaneous lesions, the data obtained from a large number of inhalation and non-inhalation studies perforated in Wistar RCCHan™: Wist rats at Harlan Laboratories Ltd Switzerland, all evaluated or reviewed by the same pathologist, were compiled for a detailed review. The value of different trimming techniques was deemed to be greatest for transverse and sagittolongitudinal section techniques, as compared to horizontolongitudinally section techniques. The comparison of lesions encountered in control rats of inhalation studies treated with different vehicles did not reveal differences in the type, distribution pattern, incidence and/or severity of spontaneous lesions. The types of lesions were also independent of different application routes in non-inhalation studies compared to inhalation studies. The pattern of spontaneous lesions in the rodent larynx was determined by degenerative and inflammatory lesions starting most often in the submucosal glands by desiccated secretion followed by mineralization and local inflammation or were induced by impacted foreign bodies. Squamous metaplasia was recorded in the respiratory epithelium overlaying the ventral gland as a spontaneous lesion in male Wistar rats from inhalation studies with a maximum of 20.0% in an inhalation oncogenicity study. Induced metaplastic changes recorded in the larynx were reversible. Other induced lesions in inhalation studies consisted of submucosal edema, necrosis, inflammation and/or granuloma. Induced lesions in non-inhalation studies were found to be exclusively related to reflux laryngitis or food impaction. It is concluded, that th rodents induced lesions of the larynx differ in type, distribution pattern, severity and incidence from spontaneous lesions. [ABSTRACT FROM AUTHOR]

The embryonated chicken egg is a well accepted test system in biomedical research. In connection with the discussion as an alternative to animal experiments, the sensitivity of the chicken embryo is a relevant issue. To assess the development and the reaction of the chicken embryo, the application of a standardized staging is neccessary. The sensitivity develops stepwise, beginning around day 7 of incubation. The extraembryonal blood vessel systems (yolk sac, chorio-allantoic-membrane) are not sensitive. In accordance with the 3 R"s, the embryonated chicken egg should be applied during early stages of development, to avoid a suffering of the embryo.

Early stages of the incubated chicken egg (appr. first third of the incubation period) are demonstrated as a model of experimental research in biology and medicine. Following a short introduction on anatomy and embryology, some advises on experimental methodology are given (application of test substances, evaluation). The application of this model is shown in several examples: as an alternative of animal experiments in ocular and mucosal toxicity, to study angiogenesis, aspects of tumour biology, or the effects of heavy metals. Furthermore, incubated eggs at day 4 of incubation can be used to investigate functional parameters of the cardiovascular system and effects of drugs on this system. Finally, the possibilities and the limitations of the test-system are discussed. It has to be pointed out that this system works in a period of incubation without any sensitivity of the embryo. Therefore, the test system using early stages of the incubated egg -- in contrast to other chicken egg models - is a real alternative to animal experiments.