Develop a standardized approach for measuring a method’s sensitivity to changes in important variables (for example, pH, ionic strength, organic matter, and biomacromolecules) and standard ways to report sensitivity.
INSTRUMENTATION
Develop new instrumentation and methods for existing instrumentation to isolate subpopulations of ENMs from polydisperse samples.

Develop tools that can detect ENMs, especially at low (relevant) concentrations in situ or in vivo, followed by methods to track and characterize ENM properties (for example, reactivity, reactive surface area, nanometer and subnanometer surface features, aggregation, and adsorption of organic macromolecules). In the future, develop methods that operate unattended and monitor ENMs in the environment in different media, especially air and water.

Develop tools to assess the rate and degree of transformation of ENMs in vivo or in situ, especially specific alteration of surface properties of ENMs due to adsorption of proteins and
lipids (corona formation) and NOM.
MODELS
Develop models to estimate sources of ENMs released into the environment along a material’s life cycle and value chain.

Modify traditional exposure models to include processes that affect ENM distribution in the environment and influence human exposure (for example, attachment to environmental and biologic surfaces, degradation rate, and dilution) and determine how to assign values to parameters in those models.

Determine toxicity pathways for outcomes (for example, effects on survival and reproduction) that predict population effects of ENM exposure and formulate ecotoxicity models, using data on sublethal toxicity end points (including effects on growth, behavior, reproduction, development, and metabolism).

Update inhalation models to include dependence on ENM shape, surface properties, and agglomeration on deposition efficiency, and the underlying mechanisms of deposition of inhaled ENMs in the respiratory tract.

Identify pathways of elimination of ENMs after their biodistribution and accumulation in primary and secondary organs. Determine principle mechanisms of elimination as inputs into predictive bioinformatics modeling.

Identify key uncertainties and sensitivities surrounding exposure assessment and effects models, estimate the ranges of the uncertainties and sensitivities, and incorporate the uncertainties into the models.
INFORMATICS
Identify minimum characterization principles to develop standardized descriptors (that is, metadata) for ENMs that are related to their key physical material characteristics for reporting and cross-referencing data on ENM properties and effects.

Establish uniform metadata to describe ENM manufacturing and distribution processes and to correlate lotto-lot variability of ENM properties with changes in synthesis and handling.

Develop ontologies and data formats to allow relevant data on gene and protein expression to be correlated with ENM-toxicity mechanisms.

Develop strategies for federating nanotechnology databases administered by different agencies, business entities, universities, and nongovernment organizations to allow seamless data exposure and data-sharing while protecting intellectual-property rights.

Develop new mechanisms for digital archiving and annotating and updating of methods, data, tools, and models to spur rapid and efficient formation of new targeted national and international scientific collaborations.

Develop and augment ontologies to support nanotechnology and nanoscience and in particular to develop an ontology “crawler” to aid in mapping relationships among ontologies.


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