NORA Manufacturing Sector Strategic Goals
927ZJFB - Preparation of Length-Classified Fibers for Toxicology StudiesStart Date: 4/1/2009
End Date: 9/30/2013
Principal Investigator (PI)Name: Leonid Turkevich
Funded By: NIOSH
Primary Goals Addressed5.06.0
Secondary Goal Addressed
Attributed to Manufacturing
The objective of this project is to develop and construct an instrument facility capable of producing length-selected fibers (e.g. asbestos) in quantities sufficient for in vivo and in vitro toxicological studies. Successful instrument development will enable toxicology studies to test directly the importance of fiber length in asbestos-related diseases: asbestosis, lung cancer, mesothelioma.
NIOSH has developed a dielectrophoresis technique for generating size-selected fractions of fibers by length [Baron et al. 1994]. The technique, in its current analytical implementation, is only capable of processing small quantities of fibers.
The proposed project seeks to develop techniques to separate the larger quantities needed for in vivo and in vitro studies. The original Baron classifier instrument has already proven its ability to length classify fibers [Deye et al. 1999] and has been used in earlier, small-scale in vitro work to study the toxicological effects of classified glass microfibers [Blake et al. 1998, Ye et al. 2001, Zeidler et al. 2001].
The objective of this project is to develop a technique capable of producing length-selected fibers (e.g. asbestos) in quantities sufficient for in vivo and in vitro toxicological studies. This work will enable toxicology studies to directly test the importance of fiber length in asbestos-related diseases: asbestosis, lung cancer, mesothelioma.
Fiber length has long been suspected (Stanton hypothesis) as being a crucial parameter which determines various toxicological responses (fibrosis, lung cancer, mesothelioma) to the presence of asbestos in the lung. Direct toxicological testing has been hampered by the inability to prepare significant quantities of length-classified asbestos samples.
The 2007 NIOSH Asbestos Roadmap highlighted this important technological barrier to toxicological testing: the inability to generate large quantities of fibers in narrow length-classified size ranges has hitherto precluded any toxicological tests to ascertain the importance of fiber length in the various endpoints for fibrotic diseases. While limited inhalation studies with sizeselected refractory ceramic and glass fibers have been conducted, the proprietary (RCG, Geneva, CH) ‘water-based cyclone procedure’ is not publicly available, and hence those studies have not been independently verified or reproduced.
This project directly addresses a research area that NIOSH Respiratory Diseases have identified as important; this project will develop size-selective technology to produce dimensionally homogeneous fiber samples for experimental studies. There is significant renewed interest in asbestos-related diseases in both mitigation and mining workplaces; for example, MSHA estimates that 44,000 mine workers may be exposed to asbestos fibers or cleavage fragments.
The main product of this research will be to develop a technique to separate fibers by length for use in toxicology studies.
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