Combustion of PTFE: The effects of gravity on ultrafine particle generation

The objective of this project is to obtain an understanding of the effect of gravity on the toxicity of ultrafine particle and gas phase materials produced when fluorocarbon polymers are thermally degraded or burned. The motivation for the project is to provide a basic technical foundation on which policies for spacecraft health and safety with regard to fire and polymers can be formulated

The U.S. Environmental Protection Agency Particulate Matter Health Effects Research Centers Program: a midcourse report of status, progress, and plans.

In 1998 Congress mandated expanded U.S. Environmental Protection Agency (U.S. EPA) health effects research on ambient air particulate matter (PM) and a National Research Council (NRC) committee to provide research oversight. The U.S. EPA currently supports intramural and extramural PM research, including five academically based PM centers. The PM centers in their first 2.5 years have initiated research directed at critical issues identified by the NRC committee, including collaborative activities, and sponsored scientific workshops in key research areas. Through these activities, there is a better understanding of PM health effects and scientific uncertainties. Future PM centers research will focus on long-term effects associated with chronic PM exposures. This report provides a synopsis of accomplishments to date, short-term goals (during the next 2.5 years) and longer-term goals. It consists of six sections: biological mechanisms, acute effects, chronic effects, dosimetry, exposure assessment, and the specific attributes of a coordinated PM centers program

The Role of Response-metric in Nanoparticle Toxicology

Thesis (Ph.D.)--University of Rochester. School of Medicine and Dentistry. Dept. of Environmental Medicine, 2009.With the increasing number and variety of NPs and the current dispute regarding the value of in vitro assays in predicting in vivo toxicity of NPs, there is an urgent need for developing and validating screening assays that work well for evaluating nanoparticle (NP) toxicity. To test the overall hypothesis that results of in vitro assays can be used to predict acute in vivo effects and to establish a hazard scale based on careful analysis of the dose-response curve using appropriate response metric, we evaluated the usefulness of several assays by adopting NP surface area as the dose metric and a response metric that is based on surface area. Several anatase TiO2 NPs (of sizes from 3 to 100 nm) were examined for this purpose. In addition to in vitro studies where a cell-free assay and several cellular assays based on a rat lung Type I epithelial cell line (R3/1) were used, we examined pulmonary inflammation or cytotoxicity related in vivo endpoints following exposure of rats to the NPs via intratracheal instillation. For the correlation studies, in vitro endpoints included ROS generation in a cell-free system, lactate dehydrogenase (LDH) release from R3/1 cells, and protein carbonylation in R3/1 cells; the in vivo endpoint was the number of neutrophils (i.e., polymorphonuclear leukocytes, PMNs) in bronchoalveolar lavage fluid (BALF) following intratracheal instillation. In addition, using several other types of NPs (a titanium dioxide NP P-25, a copper, and two silver NPs), the LDH assay was evaluated via LDH inactivation studies in different media with or without the presence of NPs and via several other experiments such as oxidation of NADH by NPs. We found that most of the NPs we studied (except a copper NP and a carbon-containing silver NP) did not cause a significant interference with the assay. Protein carbonylation was a good marker for oxidative stress related toxicity for most of the NPs except silver particles. The in vitro and in vivo data were well correlated when using the steepest slopes in the dose-response curves for correlation analysis and when using surface area as the basis for dose- and response-metrics, suggesting that proper dose- and response-metrics are important for evaluating in vivo – in vitro correlations. We conclude that toxicity rankings based on certain in vitro assays reflect well the in vivo toxicity rankings when proper dose and response metrics were utilized. This work points the way to developing models for predicting in vivo toxicity of NPs based on data from validated in vitro screening assays. Such correlation and prediction studies will be increasingly important for rapid screening of NP toxicity via the development and validation of high-throughput in vitro assays. Such an effort will be as promising as, if not more promising than, quantitative structure-activity relationship (QSAR) techniques that are being assessed by several research groups for predicting NP toxicity based on complex physicochemical properties of NPs