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An NTP Caveat - Predictive Toxicity and Nanomaterials

By Eddy Ball
September 2009

Walker, Nigel
Walker has been the NTP lead on the potential health risks posed by exposure to nanoscale materials in the environment.
(Photo courtesy of Steve McCaw)

Bucher, John
Bucher, who assumed leadership of NTP in 2007, is guiding the organization as it evolves to meet the needs of toxicology in the 21st century. (Photo courtesy of Steve McCaw)

In a forum series article published in the August issue of Toxicological Sciences, National Toxicology Program (NTP)(http://www.niehs.nih.gov/research/atniehs/dntp/index.cfm) Deputy Program Director for Science Nigel Walker, Ph.D., and NTP Associate Director John Bucher, Ph.D., take a critical look at the 21st century paradigm for evaluating the health hazards of nanoscale materials. Walker and Bucher explore the strengths and weaknesses of applying high-throughput predictive toxicity strategies to assessment of the potential health risks of the proliferating number and types of nanomaterials now in use or currently in development.

NTP and other organizations are involved in proactive efforts to move toxicology from a predominantly observational science to a predominately predictive one by integrating new high-throughput screening (HTS) technologies. As outlined in the National Research Council (NRC) report "Toxicity Testing in the 21st Century,"(http://www.nap.edu/catalog.php?record_id=11970) Exit NIEHS HTS may be key to developing predictive models for anticipating in vivo biological responses to chemical exposures. Recently, several predictive methodologies have been proposed for applying the NRC paradigm to studies of existing and emerging nanoscale materials.

In their paper(http://www.ncbi.nlm.nih.gov/pubmed/19468057?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_Default
ReportPanel.Pubmed_RVDocSum)
Exit NIEHS, the authors concede, "It is clear that a one-by-one approach to toxicity testing [of nanoscale materials] is not a tenable strategy." However, they also argue that, unlike chemicals and other simpler substances, nanoscale materials present new and different challenges for assessment because of their various sizes and shapes, differing composition from manufacturer to manufacturer, engineering and sometimes unpredictable behaviors, such as agglomeration and aggregation - all of which contribute to making chemical characterization and determination of dosimetry "an area that requires significantly more attention [in HTS screening] than would be paid to most chemicals."

Along with these factors, the testing environment itself may create special issues for determining what is "purity" for a nanomaterial in the assessment of its appropriate physicochemical properties. "The specific composition of an in vitro and in vivo test system will likely play a huge role in how a nanomaterial interacts with a cell or other biological target," Walker and Bucher contend. "What was 'tested' may often bear little resemblance to the material as it exists in the real world or in a different test system."

While Walker and Bucher admit that some nanomaterials may offer "a tailor-made test case" for the new paradigm, they suggest that "the healthy debate among toxicologists, regulators and the public at large" over this issue will continue. With so much still to be understood about nanoscale materials, the authors warn, "by virtue of their physical attributes and unpredictable and/or artifactual behavior in in vitro systems, the majority of nanomaterials may not be amendable to study in high throughput assays."

Citation: Walker NJ, Bucher JR.(http://www.ncbi.nlm.nih.gov/pubmed/19468057?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum) Exit NIEHS 2009. A 21st century paradigm for evaluating the health hazards of nanoscale materials? Toxicol Sci 110(2):251-4. [Epub before print]



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