Implementation of alternative test strategies for the safety assessment of engineered nanomaterials
Version of Record online: 23 JUL 2013
© 2013 The Association for the Publication of the Journal of Internal Medicine
Journal of Internal Medicine
Volume 274, Issue 6, pages 561–577, December 2013
How to Cite
Abstract. David Geffen School of Medicine, University of California; California NanoSystems Institute, University of California, Los Angeles (UCLA); Center for Environmental Implications of Nanotechnology, University of California; UCLA Center for Nano Biology and Predictive Toxicology, Los Angeles, CA, USA. Implementation of alternative test strategies for the safety assessment of engineered nanomaterials (Review).( J Intern Med 2013; 274: 561–577.
- Issue online: 11 NOV 2013
- Version of Record online: 23 JUL 2013
- US Public Health Service. Grant Number: U19 ES019528
- National Science Foundation and the Environmental Protection Agency. Grant Number: DBI-0830117
- alternative test strategies;
- predictive toxicology;
- safety assessment
Nanotechnology introduces a new field that requires novel approaches and methods for hazard and risk assessment. For an appropriate scientific platform for safety assessment, nanoscale properties and functions of engineered nanomaterials (ENMs), including how the physicochemical properties of the materials relate to mechanisms of injury at the nano–bio interface, must be considered. Moreover, this rapidly advancing new field requires novel test strategies that allow multiple toxicants to be screened in robust, mechanism-based assays in which the bulk of the investigation can be carried out at the cellular and biomolecular level whilst maintaining limited animal use and is based on the contribution of toxicological pathways to the pathophysiology of disease. First, a predictive toxicological approach for the safety assessment of ENMs will be discussed against the background of a ‘21st-century vision’ for using alternative test strategies (ATSs) to perform toxicological assessment of large numbers of untested chemicals, thereby reducing a backlog that could otherwise become a problem for nanotechnology. An ATS is defined here as an alternative to animal experiments or refinement/reduction alternative to traditional animal testing. Secondly, the approach of selecting pathways of toxicity to screen for the pulmonary hazard potential of carbon nanotubes and metal oxides will be discussed, as well as how to use these pathways to perform high-content or high-throughput testing and how the data can be used for hazard ranking, risk assessment, regulatory decision-making and ‘safer-by-design’ strategies. Finally, the utility and disadvantages of this predictive toxicological approach to ENM safety assessment, and how it can assist the 21st-century vision, will be addressed.