Recommendations for nanomedicine human subjects research oversight: an evolutionary approach for an emerging field.

The nanomedicine field is fast evolving toward complex, "active," and interactive formulations. Like many emerging technologies, nanomedicine raises questions of how human subjects research (HSR) should be conducted and the adequacy of current oversight, as well as how to integrate concerns over occupational, bystander, and environmental exposures. The history of oversight for HSR investigating emerging technologies is a patchwork quilt without systematic justification of when ordinary oversight for HSR is enough versus when added oversight is warranted. Nanomedicine HSR provides an occasion to think systematically about appropriate oversight, especially early in the evolution of a technology, when hazard and risk information may remain incomplete. This paper presents the consensus recommendations of a multidisciplinary, NIH-funded project group, to ensure a science-based and ethically informed approach to HSR issues in nanomedicine, and to integrate HSR analysis with analysis of occupational, bystander, and environmental concerns. We recommend creating two bodies, an interagency Human Subjects Research in Nanomedicine (HSR/N) Working Group and a Secretary's Advisory Committee on Nanomedicine (SAC/N). HSR/N and SAC/N should perform 3 primary functions: (1) analysis of the attributes and subsets of nanomedicine interventions that raise HSR challenges and current gaps in oversight; (2) providing advice to relevant agencies and institutional bodies on the HSR issues, as well as federal and federal-institutional coordination; and (3) gathering and analyzing information on HSR issues as they emerge in nanomedicine. HSR/N and SAC/N will create a home for HSR analysis and coordination in DHHS (the key agency for relevant HSR oversight), optimize federal and institutional approaches, and allow HSR review to evolve with greater knowledge about nanomedicine interventions and greater clarity about attributes of concern.

Nano risk analysis: advancing the science for nanomaterials risk management.

Scientists, activists, industry, and governments have raised concerns about health and environmental risks of nanoscale materials. The Society for Risk Analysis convened experts in September 2008 in Washington, DC to deliberate on issues relating to the unique attributes of nanoscale materials that raise novel concerns about health risks. This article reports on the overall themes and findings of the workshop, uncovering the underlying issues for each of these topics that become recurring themes. The attributes of nanoscale particles and other nanomaterials that present novel issues for risk analysis are evaluated in a risk analysis framework, identifying challenges and opportunities for risk analysts and others seeking to assess and manage the risks from emerging nanoscale materials and nanotechnologies. Workshop deliberations and recommendations for advancing the risk analysis and management of nanotechnologies are presented.

Exposure assessment approaches for engineered nanomaterials.

Products based on nanotechnology are rapidly emerging in the marketplace, sometimes with little notice to consumers of their nanotechnology pedigree. This wide variety of nanotechnology products will result (in some cases) in unintentional human exposure to purposely engineered nanoscale materials via the dermal, inhalation, ingestion, and ocular pathways. Occupational, consumer, and environmental exposure to the nanomaterials should be characterized during the entire product lifecycle-manufacture, use, and disposal. Monitoring the fate and transport of engineered nanomaterials is complicated by the lack of detection techniques and the lack of a defined set of standardized metrics to be consistently measured. New exposure metrics may be required for engineered nanomaterials, but progress is possible by building on existing tools. An exposure metric matrix could organize existing data by relating likely exposure pathways (dermal, inhalation, ocular, ingestion) with existing measurements of important characteristics of nanoscale materials (particle number, mass, size distribution, charge). Nanomaterial characteristics not commonly measured, but shown to initiate a biological response during toxicity testing, signal a need for further research, such as the pressing need to develop monitoring devices capable of measuring those aspects of engineered nanomaterials that result in biological responses in humans. Modeling the behavior of nanoparticles may require new types of exposure models that individually track particles through the environment while keeping track of the particle shape, surface area, and other surface characteristics as the nanoparticles are transformed or become reactive. Lifecycle analysis could also be used to develop conceptual models of exposure from engineered nanomaterials.

Commentary: Oversight of engineered nanomaterials in the workplace.

Research and business investment in emerging nanotechnologies is leading to a diverse range of new substances and products. As workers are faced with handling new materials, often with novel properties, the robustness of current workplace health and safety regulatory frameworks is being brought into question. Here, 12 characteristics of the U.S. occupational safety regulatory framework identified by Choi and Ramachandran are considered in the context of emerging nanotechnologies. The assessment suggests that, as the number of new materials entering the workplace continues to increase, OSHA will need to develop flexible approaches to identifying and reducing potential risks. Relying on conventional approaches in the face of unconventional challenges will increase the probability of otherwise avoidable heath impacts. If the potential for engineered nanomaterials to cause harm is to be understood and managed, the agency will need to look at new approaches to generating, sharing, and using information.

Meeting report: hazard assessment for nanoparticles--report from an interdisciplinary workshop.

In this report we present the findings from a nanotoxicology workshop held 6-7 April 2006 at the Woodrow Wilson International Center for Scholars in Washington, DC. Over 2 days, 26 scientists from government, academia, industry, and nonprofit organizations addressed two specific questions: what information is needed to understand the human health impact of engineered nanoparticles and how is this information best obtained? To assess hazards of nanoparticles in the near-term, most participants noted the need to use existing in vivo toxicologic tests because of their greater familiarity and interpretability. For all types of toxicology tests, the best measures of nanoparticle dose need to be determined. Most participants agreed that a standard set of nanoparticles should be validated by laboratories worldwide and made available for benchmarking tests of other newly created nanoparticles. The group concluded that a battery of tests should be developed to uncover particularly hazardous properties. Given the large number of diverse materials, most participants favored a tiered approach. Over the long term, research aimed at developing a mechanistic understanding of the numerous characteristics that influence nanoparticle toxicity was deemed essential. Predicting the potential toxicity of emerging nanoparticles will require hypothesis-driven research that elucidates how physicochemical parameters influence toxic effects on biological systems. Research needs should be determined in the context of the current availability of testing methods for nanoscale particles. Finally, the group identified general policy and strategic opportunities to accelerate the development and implementation of testing protocols and ensure that the information generated is translated effectively for all stakeholders.

Research strategies for safety evaluation of nanomaterials, part IV: risk assessment of nanoparticles.

Nanoparticles are small-scale substances (<100 nm) with unique properties and, thus, complex exposure and health risk implications. This symposium review summarizes recent findings in exposure and toxicity of nanoparticles and their application for assessing human health risks. Characterization of airborne particles indicates that exposures will depend on particle behavior (e.g., disperse or aggregate) and that accurate, portable, and cost-effective measurement techniques are essential for understanding exposure. Under many conditions, dermal penetration of nanoparticles may be limited for consumer products such as sunscreens, although additional studies are needed on potential photooxidation products, experimental methods, and the effect of skin condition on penetration. Carbon nanotubes apparently have greater pulmonary toxicity (inflammation, granuloma) in mice than fine-scale carbon graphite, and their metal content may affect toxicity. Studies on TiO2 and quartz illustrate the complex relationship between toxicity and particle characteristics, including surface coatings, which make generalizations (e.g., smaller particles are always more toxic) incorrect for some substances. These recent toxicity and exposure data, combined with therapeutic and other related literature, are beginning to shape risk assessments that will be used to regulate the use of nanomaterials in consumer products.