MWCNTs of different physicochemical properties cause similar inflammatory responses, but differences in transcriptional and histological markers of fibrosis in mouse lungs

Multi-walled carbon nanotubes (MWCNTs) are extensively produced and used in composite materials and electronic applications, thus increasing risk of worker and consumer exposure. MWCNTs are an inhomogeneous group of nanomaterials that come in various lengths, shapes and with different metal contaminations, which makes hazard evaluation difficult. However, several studies suggest that length plays an important role in the toxicity induced by MWCNTs. How the length influences toxicity at the molecular level is yet to be characterized. Female C57BL/6 mice were exposed by single intratracheal instillation to 18, 54 or 162 µg/mouse of a short MWCNT (NRCWE-026, 847±102 nm in length) or long MWCNT (NM-401, 4048±366 nm in length). The two MWCNTs were extensively characterized. Lung tissues were harvested 24 h, 3 d and 28 d after exposure. We employed DNA microarrays, bronchoalveolar lavage fluid analysis, comet assay and dichlorodihydrofluorescein assay in order to profile the pulmonary responses. Bioinformatics tools were then applied to compare and contrast the expression profiles and to build a length dependent property-response matrix for gene-by-gene comparison. The toxicogenomic analysis of the global mRNA changes after exposure to the short, entangled NRCWE-026 or the longer, stiffer NM-401 showed high degree of similarities. The toxicity of both MWCNTs was driven by strong inflammatory and acute phase responses, which peaked at day 3 and was observed both in bronchoalveolar lavage cell influx and in gene expression profiles. The inflammatory response was sustained at post-exposure day 28. Also, at the sub-chronic level, we identified a sub-set of 14 fibrosis related genes that were uniquely differentially regulated after exposure to NM-401. Acellular ROS production occurred almost exclusively with NRCWE-026, however the longer NM-401 induced in vivo DNA strand breaks and differential regulation of genes involved in free radical scavenging more readily than NRCWE-026. Our results indicate that the global mRNA response after exposure to MWCNTs is length independent at the acute time points, but that fibrosis may be length dependent sub-chronic end point.JRC.H.6-Digital Earth and Reference Dat

Histopathological analysis of tumour types after intraperitoneal injection of mineral fibers in rats

Female rats were treated twice by an intraperitoneal injection of mineral fibres. The treatment led to malignant tumours in the peritoneal cavity. Most of these tumours were classified as malignant mesotheliomas. Some rats had undifferentiated sarcomas rather than mesotheliomas. Three different types of malignant mesotheliomas can be distinguished: epithelioid, sarcomatoid and mixed. Cartilaginous or osseous differentiation occuring in mesotheliomas has only been described as a biological feature in a few cases of mesotheliomas of the pleura in man (Goldstein, 1979; McCaughey, 1958; Yousem and Hochholzer, 1987). Some of the affected persons were known to have been exposed to asbestos (Goldstein, 1979; Yousem and Hochholzer, 1987). In the following report histopathological features of malignant mesotheliomas occurring in the abdominal cavity after intraperitoneal injection of different types of mineral fibres in female Wistar rats are described. Additionally, the number of animals with mesotheliomas, according to the injected fibre type is presented

Histological observations and morphometric analysis in lungs of hamsters after long term inhalation of cadmium compounds

Long term inhalation studies with Syrian hamsters were performed to evaluate the effects of different cadmium compounds on the lung of this species. No tumours were observed in the lung of the hamsters. Bronchiolization is localized at the bronchiolar-alveolar junction. The walls of the respiratory bronchioles, alveolar ducts and adjacent alveoli become replaced by cuboidal ciliated cells. Interstitial fibrosis was observed in a significantly high frequency

Tierexperimentelle Kanzerogenitaetsstudie ueber die Kombinationswirkung von Kohleverbrennungsabgas (mit PAH angereichert) mit zwei Metallverbindungen und Asbest

With 15 refs., 8 tabs., 20 figs.SIGLECopy held by FIZ Karlsruhe; available from UB/TIB Hannover / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekDEGerman

Proliferative and nonproliferative lesions of the rat and mouse respiratory tract

The INHAND Project (International Harmonization of and Diagnostic Criteria for Lesions in Rats and Mice) is a joint initiative of the Societies of Toxicologic Pathology from Europe (ESTP). Great Britain (BSTP). Japan (JSPT) and North America (STP) to develop an internationally-accepted nomenclature for proliferative and non-proliferative lesions in laboratory animals. The purpose of this publication is to provide a standardized nomenclature for classifying microscopic lesions observed in the respiratory tract of laboratory rats and mice, with color photomicrographs illustrating examples of some lesions. The standardized nomenclature presented in this document is also available electronically on the internet (http.//www gorem org/) Sources of material included histopathology databases from government, academia, and industrial laboratories throughout the world. Content includes spontaneous developmental and aging lesions as well as lesions induced by exposure to test materials. A widely accepted and utilized international harmonization of nomenclature for respiratory tract lesions in laboratory animals will decrease confusion among regulatory and scientific research organizations in different countries and provide a common language to increase and enrich international exchanges of information among toxicologists and pathologists

International Harmonization of Nomenclature and Diagnostic Criteria (INHAND) Progress to Date and Future Plans

Standardization of microscopic pathology nomenclature and diagnostic criteria, especially for rats and mice, has been under discussion for many years by pathologists in the profession of toxicologic pathology. In 2005, the Society of Toxicologic Pathology (STP) and European Society of Toxicologic Pathology (ESTP), along with Registry of Industrial Toxicology Animal-data (RITA), established a collaborative process to review, update, and harmonize existing nomenclature documents and databases. The British Society of Toxicologic Pathology (BSTP) and the Japanese Society of Toxicologic Pathology (JSTP) joined the project in 2006, making this a genuinely global initiative. The result of these discussions was the INHAND Proposal (International Harmonization of Nomenclature and Diagnostic Criteria for Lesions in Rats and Mice). A Global Editorial Steering Committee (GESC) manages the overall objectives of the project, and Working Groups (WG) formulate the terminology proposals for each organ system (Vahle et al, 2009). Both the GESC and the WGs are composed of experts from the North American, British and European and Japanese Societies of Toxicologic Pathology

International Harmonization of Nomenclature and Diagnostic Criteria (INHAND) Progress to Date and Future Plans

Standardization of microscopic pathology nomenclature and diagnostic criteria, especially for rats and mice, has been under discussion for many years by pathologists in the profession of toxicologic pathology. In 2005, the Society of Toxicologic Pathology (STP) and European Society of Toxicologic Pathology (ESTP), along with Registry of Industrial Toxicology Animal-data (RITA), established a collaborative process to review, update, and harmonize existing nomenclature documents and databases. The British Society of Toxicologic Pathology (BSTP) and the Japanese Society of Toxicologic Pathology (JSTP) joined the project in 2006, making this a genuinely global initiative. The result of these discussions was the INHAND Proposal (International Harmonization of Nomenclature and Diagnostic Criteria for Lesions in Rats and Mice). A Global Editorial Steering Committee (GESC) manages the overall objectives of the project, and Working Groups (WG) formulate the terminology proposals for each organ system (Vahle et al, 2009). Both the GESC and the WGs are composed of experts from the North American, British and European and Japanese Societies of Toxicologic Pathology

Pruefung von Kohleverbrennungsabgas (mit PAH angereichert) auf kanzerogene und andere chronisch-toxische Effekte im Tierversuch

With 18 refs., 52 tabs., 51 figs.SIGLECopy held by FIZ Karlsruhe; available from UB/TIB Hannover / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekDEGerman