Comprehensive evaluation of the flavonol anti-oxidants, alpha-glycosyl isoquercitrin and isoquercitrin, for genotoxic potential.

Quercetin and its glycosides possess potential benefits to human health. Several flavonols are available to consumers as dietary supplements, promoted as anti-oxidants; however, incorporation of natural quercetin glycosides into food and beverage products has been limited by poor miscibility in water. Enzymatic conjugation of multiple glucose moieties to isoquercitrin to produce alpha-glycosyl isoquercitrin (AGIQ) enhances solubility and bioavailability.

Analysis of negative historical control group data from the in vitro micronucleus assay using TK6 cells.

The recent revisions of the Organisation for Economic Co-operation and Development (OECD) genetic toxicology test guidelines emphasize the importance of historical negative controls both for data quality and interpretation. The goal of a HESI Genetic Toxicology Technical Committee (GTTC) workgroup was to collect data from participating laboratories and to conduct a statistical analysis to understand and publish the range of values that are normally seen in experienced laboratories using TK6 cells to conduct the in vitro micronucleus assay. Data from negative control samples from in vitro micronucleus assays using TK6 cells from 13 laboratories were collected using a standard collection form.

The role of ethyl acrylate induced GSH depletion in the rodent forestomach and its impact on MTD and in vivo genotoxicity in developing an adverse outcome pathway (AOP).

Adverse outcome pathways (AOP) and mode of action (MOA) frameworks help evaluate the toxicity findings of animal studies and their relevance to humans. To effectively use these tools to improve hazard identification and risk assessments for ethyl acrylate (EA), knowledge gaps in metabolism and genotoxicity were identified and addressed. For EA, hypothesized early key events relate to its irritation potential: concentration dependent irritation and cytotoxicity, progressing to regenerative proliferation and forestomach carcinogenicity after repeated oral bolus application in rodents.

A 104-week pulmonary toxicity assessment of long and short single-wall carbon nanotubes after a single intratracheal instillation in rats.

We compared long-term pulmonary toxicities after a single intratracheal instillation of two types of dispersed single-wall carbon nanotubes (SWCNTs), namely, those with relatively long or short linear shapes with average lengths of 8.6 and 0.55 µm, respectively.

Reference control data obtained from an in vivo comet-micronucleus combination assay using Sprague Dawley rats.

According to the International Conference on Harmonization Guidance on Genotoxicity Testing and Data Interpretation for Pharmaceuticals Intended for Human Use (ICH S2(R1)), a positive response in any in vitro assay necessitates additional in vivo test(s) (other tissue/endpoint) in addition to the erythrocyte micronucleus test when Option 1 of the test battery is selected. When Option 2 of the test battery is selected, a bacterial gene mutation test and two in vivo tests with different tissues/endpoint are required. The in vivo alkaline comet assay is recommended as the second in vivo test because it can detect a broad spectrum of DNA damage in any tissue and can be combined with the erythrocyte micronucleus test.

Long-term retention of pristine multi-walled carbon nanotubes in rat lungs after intratracheal instillation.

As a result of the growing potential industrial and medical applications of multi-walled carbon nanotubes (MWCNTs), people working in or residing near facilities that manufacture them may be exposed to airborne MWCNTs in the future. Because of concerns regarding their toxicity, quantitative data on the long-term clearance of pristine MWCNTs from the lungs are required. We administered pristine MWCNTs well dispersed in 0.

Risk Assessment of the Carbon Nanotube Group.

This study assessed the health risks via inhalation and derived the occupational exposure limit (OEL) for the carbon nanotube (CNT) group rather than individual CNT material. We devised two methods: the integration of the intratracheal instillation (IT) data with the inhalation (IH) data, and the "biaxial approach." A four-week IH test and IT test were performed in rats exposed to representative materials to obtain the no observed adverse effect level, based on which the OEL was derived.

Hepatic Lesions Caused by Large Granular Lymphocyte Leukemia in Fischer 344 Rats: Similar Morphologic Features and Morphogenesis to Those of Nodular Regenerative Hyperplasia (NRH) in the Human Liver.

To characterize the hepatic lesions in Fischer 344 (F344) rats afflicted with large granular lymphocyte (LGL) leukemia, the livers of rats with LGL leukemia at various stages were examined histopathologically and immunohistochemically. The morphologic features in the livers of rats afflicted with LGL leukemia were diffuse, uniform-sized, granular, or micronodular lesions consisting of hepatocytes showing centrilobular atrophy and perilobular hypertrophy (CAPH) without fibrosis. With progression in the stage of the LGL leukemia, the severity of the CAPH of hepatocytes increased resulting in fatty change and/or single-cell necrosis, along with compensatory hyperplasia of the hepatocytes, finally resulting in lesions similar to those seen in nodular regenerative hyperplasia (NRH) in the human liver.

Repeated-dose liver and gastrointestinal tract micronucleus assays for quinoline in rats.

Repeated-dose liver, bone marrow, and gastrointestinal tract micronucleus assays that use young adult rats were evaluated in a collaborative study that was organized by the Japanese Environmental Mutagen Society-Mammalian Mutagenicity Study Group. A genotoxic hepatocarcinogen quinoline was orally administered to independent groups of five Crl:CD (SD) male rats at doses of 30, 60 and 120mg/kg for 14 days and at doses of 15, 30 and 60mg/kg for 28 days. After treatment, the livers were harvested and hepatocytes were isolated by collagenase treatment.

Flow cytometric analysis of micronuclei in rat peripheral blood: An interlaboratory reproducibility study.

In anticipation of proposed OECD guideline changes that may include increasing the number of reticulocytes scored for micronuclei, an inter-laboratory reproducibility study of the rat peripheral blood micronucleus assay was performed using flow cytometry. In this experiment, male Sprague-Dawley (SD) rats were treated with the model clastogen cyclophosphamide (CP: 5, 10 or 15mg/kg) by a single oral administration. As controls, rats were treated with physiological saline (solvent) in the same manner as for the model clastogen.

Lung toxicity assessment using bronchoalveolar lavage fluid and pleural lavage fluid cytology by intratracheal treatment in rats.

Usefulness of bronchoalveolar lavage fluid (BALF) and pleural cavity lavage fluid (PLF) as an experimental material was evaluated for the assessment of pulmonary toxicity of chemicals in rats. From the viewpoint of safety, isoflurane can be used for euthanasia/anesthesia because there was no difference in biological properties of BALF between diethyl ether and isoflurane. Here, we also recognized phosphate buffered saline (PBS) and distilled water equally as a solvent/vehicle for negative control.