Ensuring Appropriate Material Characterization in Nano-toxicity Studies

Workshop Summary

A workshop was held at the Woodrow Wilson Center in Washington DC between Oct 28 – 29 2008, with two aims:

• To develop minimal material characterization recommendations for nano-toxicology studies; and
• To develop a plan of action for encouraging adoption of these recommendations by researchers, research managers and research publishers.

This is a draft summary of workshop findings:

Purpose

• To develop minimal material characterization recommendations for nano-toxicology studies; and
• To develop a plan of action for encouraging adoption of these recommendations by researchers, research managers and research publishers.

Intended Outcomes

• Raise the bar for nanomaterial toxicology research, including
  • Facilitating/encouraging appropriate materials characterization in nano-toxicity studies
  • Fostering a culture of good nanomaterial characterization
• Enable effective use of research/increase relevance and impact of research
• Complement the work of other organizations, esp. ISO and OECD
• Encourage study designs that enable dose-response to be evaluated against alternative metrics
• Foster interdisciplinary collaborations

Anticipated Product

General guidance on nanomaterial characterization for the nanotoxicology research community (A tool that can be used by people funding, conducting, evaluating and using research)

Target Audiences

• Research Sponsors (Establishing guidelines for material characterization)
• Researchers (Generating data)
• Research evaluators (Providing a level of quality control on the dissemination of data through their existing professional and institutional responsibilities—and indirectly having an impact on study design)
• Research users (Decision-makers evaluating quality of data)

Recommended Minimum Physical and Chemical Characterization Parameters
What does the material look like?

• Particle size/size distribution
• Agglomeration state/Aggregation
• Shape

What is the material made of?

• Overall composition (including chemical composition and crystal structure)
• Surface Composition
• Purity (including levels of impurities)

What factors affect how a material interacts with its surroundings?

• Surface Area
• Surface Chemistry, including reactivity, hydrophobicity
• Surface Charge

Overarching considerations

• Stability—how do material properties change with time (dynamic stability), storage, handling, preparation, delivery etc?  Include solubility, and the rate of material release through dissolution.
• Context/Media—how do material properties change in different media; i.e. from the bulk material to dispersions to material in various biological matrices? (“as administered” characterization is considered to be particularly important)
• Where possible, materials should be characterized sufficiently to interpret the response to the amount of material against a range of potentially relevant dose metrics, including mass, surface-area and number concentration.

Notes

This framework is designed to stimulate appropriate characterization, while complimenting more specific guidance from organizations such as ISO and OECD.

Highlighting a key set of parameters without specifying prescriptive approaches to characterizing them is intentional, as an approach to fostering a culture of effective characterization without stifling innovation, developing a set of recommendations that are more likely to be considered by relevant communities, and allowing these recommendations to support the adoption of more authoritative guidelines from other sources. Furthermore, the intentional omission of defined methods is meant to foster discussions between researchers in the biological sciences and the materials sciences, both of whom play a role in characterizing the effects of nanomaterials on biological systems.

It was a shared view that inter-laboratory comparison studies, known to be desirable, are infrequent due to issues surrounding funding and accepted laboratory protocols.

Reference should be made to internationally recognized terms and definitions (e.g. ISO TC229), and to federally-funded institutions capable of providing characterization services.

Next Steps

• Consider establishing an independent web-based resource outlining the motivation, conclusions and recommendations of the workshop
• Develop a system to enable practitioners/stakeholders to sign up in support of the recommendations
• Publish a high profile article on the recommendations, and a path toward more appropriate nanomaterial characterization in toxicology studies