can be linked to biologic-nanotechnologic or ecologic-nanotechnologic interactions or end points. Reference materials are often highly purified to reduce or eliminate the effects of impurities on responses (Oostingh et al. 2011). They may not attain the same level of scrutiny as standards (see discussion below), but they require a smaller investment of time and resources to develop. Sources of these materials include academic and government research laboratories (National Institute of Standards and Technology), commercial suppliers (for example, nanoComposix, Nanoprobes, Inc., and Strem Chemicals, Inc.), and international harmonization efforts (such as the Organisation for Economic Cooperation and Development and the International Alliance for NanoEHS Harmonization). Standard or reference materials can be used to compare test or measurement results among laboratories or to compare the results from different tests or measurements. However, because these materials typically represent specific, narrow structural types that are not easily manipulated to access a broad range of structural features, it is difficult to develop more general design rules from studies of these materials.


Libraries are collections of reference materials in which structural or compositional variables are systematically varied throughout a series of members of the library. For example, the nanoparticle core material and size might be kept constant while a surface coating varies in its external charge—positively, negatively, or not at all. Libraries allow the influence of nanomaterial structure and composition on biologic or ecologic effects to be explored so that quantitative structure-activity relationships can be determined. Libraries also facilitate exploration of hypotheses related to material-effect correlations. To serve that purpose, libraries should be appropriately defined and characterized as described above for reference materials. Ideally, the materials in libraries have sufficient range and granularity across the structural or compositional measures of interest. Given the importance of detailed characterization for establishing cause-effect correlations, characterization data on each sample lot need to be provided with each sample.


Standards are samples that have been thoroughly tested to support laboratory comparisons or to calibrate and harmonize measurements conducted in different laboratories. They typically are prepared and provided for by standard-setting organizations or agencies (for example, the National Institute of Standards and Technology). The benefits of developing standard materials that meet the criteria for definition and characterization are clear; however, the time (years) and expense of developing such standards sometimes restrict their use in EHS studies.

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