Chair of Session 3 & 4
Dr Michaela Kendall, University of Southampton, UK
Nanoparticles entering the human lung
Professor Howard Clark, University of Southampton, UK
The lung surfactant system is a complex lipoprotein mixture which lines the alveoli of the lungs and reduces surface tension, preventing lung collapse on exhalation. It has become clear that this surfactant layer also acts in defence of the lung from inhaled potentially injurious or toxic materials including microbes, allergens and nano particulate pollutants. We have described how components of surfactant, specifically surfactant proteins A and D , interact with nanoparticles and shown that nanoparticles interact differently with lung surfactant depending on their surface chemistry. Surfactant proteins are critical regulators of lung inflammation and we show how disruption of their function by nanoparticles may affect their efficiency in protecting the lung from inflammation and infection. By subverting these natural defence mechanisms of the lung, nanoparticles may persist in the respiratory tract, translocate into the circulation and potentially contribute to both respiratory and systemic disease.
Nanoparticles in the gastrointestinal tract: exposure, absorption and utilisation are normal physiological processes but imposters take advantage
Dr Jonathan Powell, MRC HNR, UK
There are, in fact, purposeful pathways for nanomineral uptake in the gastrointestinal tract, probably for nutritional and immunological reasons. Regular epithelial cells can endocytose very fine (< 10nm) nanoparticles and this is exemplified by iron oxo hydroxide, derived from various dietary/digested sources, in the proximal small bowel yielding desirable iron absorption. For larger nanoparticles the more specialised particle-scavenging M-cells of gut lymphoid follicles are the portals of entry. Particle sizes of 20-250 nm appear to be optimal for nanoparticle uptake via this route. The naturally occurring process revolves around mineralised calcium: more so, we believe, for immunological than nutritional processes. However, recent ‘nano additions’ to the human diet- namely excipients in drugs or nutraceuticals or even toothpaste, as well as nanomineral food additives- can be seen to hijack this important M cell entry point: these imposters are not yet associated with human disease but will this always be the case?
What data we have to support the use of predictive modeling and alternative strategies for regulatory decision making
Professor Andre Nel, UC Center for the Environmental Impact of Nanotechnology, USA
Nanotechnology introduces a new field requiring novel approaches and methods for hazard and risk assessment. In order to perform safety assessment, nanoscale properties and the functionality of engineered nanomaterials (ENMs) at the nano/bio interface are important considerations. This rapidly advancing 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 while limiting animal use that is based on the contribution of pathways of toxicity 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 toxicological substances. 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, metal oxides, and silica will be discussed, as well as how to use this information to perform high-content or -throughput screening. I will also describe how the data could be used for hazard ranking, risk assessment, regulatory decision-making and ‘safer-by-design’ strategies.
The challenge of nanotechnology's revolutionary change: emerging international laws
Dr Ilise L Feitshans, University of Lausanne, Switzerland
Nanotechnology has been heralded as a revolution by scientists and policymakers since 2008. Its new view of the physical properties of matter combined with the new investments it has unleashed are a major shot of adrenalin in an ailing global economy, and its promises of new medicines, lighter packaging and cheaper transport of goods offer miraculous promises for public health. Yet, the dangers of using well –established toxins and even previously innocuous substances at the nanoparticle level are unknown. Governments and policymakers are unwilling to commit to stating that nanotechnology applications in products are safe, despite their cognizance of their obligation to protect public health. Consequently, every nation and many regional organizations have created draft nanotechnology regulations. Where will this lead? It is reasonable to envision an international convention before the General Assembly of the United Nations (UN) but what can be accomplished by any new laws remains uncertain without key steps towards international harmonization. This presentation explores key regional laws impacting the UK in Council of Europe and the European Union, and discusses the pivotal role that UK can play towards international harmonization of nanotechnology regulations
Dr Iseult Lynch, University of Birmingham, UK: From bionanoscience to regulation and law – opportunities and challenges
Dr Iseult Lynch, University of Birmingham, UK
Scientists are increasingly called upon to ensure that their scientific research has wider societal impact, with nanosciences and nanotechnologies a case in point. In parallel with imagining and developing ever more innovative new materials and applications of these materials in everything from consumer products such as cosmetics, clothing and food to industrial applications such as self-healing construction materials, stronger and lighter materials for aviation and automotive industries and indeed in medicine, where their small size and “access all areas” potential has lead to them be hyped as magic bullets to address a range of currently intractible diseases, there is a need to ensure that all these developments are safe for society. Indeed few technologies have had such an ethos of safe and responsible development embedded into the researchers psyche from such an early stage of development, but then few technologies are so far-reaching in their potential.
An ongoing challenge in this new world order is for researchers to learn the lingo of those who translate scientific data into the policy, regulation and legal frameworks that ensure our safety, health and economic well-being. This is especially challenging in emerging fields, where knowledge is patchy, rapidly evolving and often utilising tools and approaches that were designed for other purposes. Safety assessment of nanomaterials is hampered by all of these issues and more – its multi-disciplinarity as a science means that researchers also have to learn to communicate across scientific boundaries, with materials scientists and engineers needing to interact with biologists, medics and toxicologists. Thus, what is common knowledge, indeed old-hat in one field, is unknown and painfully re-discovered in another, leading to (unnecessary?) errors in the scientific literature, irreproducibility of results (for often silly reasons) and increased confusion among the policy, regulatory and legal communities. So how can we move forward to ensure a more coherent approach to science to policy (i.e. regulation and/or law) communication? A suggestion is that we use the very disruptiveness of nanotechnologies to allow us to spotlight the challenges and provide an opportunity to reframe the approaches to such cross-stakeholder (cross-sectoral?) communications in the same way that the science of nanosafety is spotlighting inadequacies in existing scientific and regulatory approaches and offering new ways forward.