FDA Issues Further Nanotechnology Guidance

Late last month, the U.S. Food and Drug Administration issued one draft and three final guidance documents related to the use of nanotechnology in regulated products.

One final guidance addresses the agency’s overall approach for all products that it regulates, while the two additional final guidances and the new draft guidance provide specific guidance for the areas of foods, cosmetics and food for animals, respectively.

Readers may know from our earlier posts (and here and here) that nanotechnology is an emerging technology that allows scientists to create, explore and manipulate materials on a scale measured in nanometers—particles so small that they cannot be seen with a regular microscope. The technology has a broad range of potential applications, such as improving the packaging of food and altering the look and feel of cosmetics.

The three final guidance documents reflect the FDA’s current thinking on these issues after taking into account public comment received on the corresponding draft guidance documents previously issued (draft agency guidance in 2011; and draft cosmetics and foods guidances in 2012).

The FDA  continues to favor an approach to consider the specific characteristics of individual products. All four guidance documents encourage manufacturers to consult with the agency before taking their products to market. Consultations with the FDA early in the product development process may help to facilitate a mutual understanding about specific scientific and regulatory issues relevant to the nanotechnology product, and help address questions related to safety, effectiveness, public health impact and/or regulatory status of the product.

The guidance documents are:

Final Guidance for Industry: Considering Whether an FDA-Regulated Product Involves the Application of Nanotechnology

This guidance outlines overarching considerations for all FDA-regulated products, identifying points to consider when determining whether a product involves the use of nanotechnology. It is intended to help industry and others identify when they should consider potential implications for regulatory status, safety, effectiveness or public health impact that may arise with the application of nanotechnology in FDA-regulated products.

Final Guidance for Industry: Safety of Nanomaterials in Cosmetics

This guidance describes the FDA’s current thinking on the safety assessment of nanomaterials when used in cosmetic products and encourages manufacturers to consult with the FDA on test methods and data needed to support the substantiation of a product’s safety.

Final Guidance for Industry: Assessing the Effects of Significant Manufacturing Process Changes, Including Emerging Technologies, on the Safety and Regulatory Status of Food Ingredients and Food Contact Substances, Including Food Ingredients that are Color Additives

This guidance alerts manufacturers to the potential impact of any significant manufacturing process change, including changes involving nanotechnology, on the safety and regulatory status of food substances. This guidance also describes considerations for determining whether a significant manufacturing process change for a food substance already in the market affects the identity, safety, or regulatory status of the food substance, potentially warranting a regulatory submission to the FDA.

Draft Guidance for Industry: Use of Nanomaterials in Food for Animals

This draft guidance addresses issues related to the use of nanotechnology in food ingredients intended for use in food for animals. Public comments on this draft guidance are requested by September 10, 2014.

The FDA said it will continue to pursue ongoing scientific research and regulatory efforts and will consider new studies and data, as they become available, to determine any future actions. 

EU Offers Standard Definition of Nanotechnology

One of the challenging aspects of attempts to regulate emerging nanotechnology is the definition.  Proposing a "definition" for nanotechnology is not as straightforward a process as it may seem; applying a strict, universal definition of nanotechnology to all applicable fields and products may not be an appropriate science-based approach.  Inclusion of nanometer-sized active ingredients or excipients in a product does not by itself determine a product's safety and efficacy (i.e. size alone is not always itself an indicator of toxicity).   Then there is the issue of distinguishing between engineered nanomaterials and those naturally occurring at the nanoscale.

Last week, the European Commission took another step in this debate, unveiling a new, common nanomaterial definition as a basis for regulation. Nanomaterials are defined as those whose main constituents measure between 1 and 100 billionth of a meter; that is, a natural, incidental or manufactured material containing particles, in an unbound state or as an aggregate or as an agglomerate and where, for 50% or more of the particles in the number size distribution, one or more external dimensions is in the target size range.

Thus, the new EU definition is based on an approach that considers the size of the constituent particles, rather than any other indicia of potential risk.  The EU did note that there is no evidence that nanomaterials are inherently hazardous. Technological development and scientific progress continue with great speed, noted the report. The definition including descriptors will therefore be subject to a re-review by December 2014. In particular, the review will assess whether the number size distribution threshold of 50 % should be increased or decreased and whether to include materials with internal structure or surface structure in the nanoscale such as complex nano-component nanomaterials including nanoporous and nano-composite materials that are used in some product sectors.

 

CHPA Comments on Draft FDA Guidance on Nanotechnology

Last week, the Consumer Healthcare Products Association (CHPA) submitted comments on the FDA’s draft guidance on nanotechnology, "Considering Whether an FDA-Regulated Product Involves the Application of Nanotechnology, "  which we posted on before.

CHPA is the not-for-profit association representing the makers of over-the-counter medicines and dietary supplements, and the consumers who rely on these healthcare products. CHPA is one of the oldest trade associations in the United States. Nanotechnology holds great promise for this industry.

CHPA agreed with the FDA that proposing a "definition" for nanotechnology is not a straight forward process; applying a strict, universal definition of nanotechnology to the fields of drug research, drug product development and drug manufacturing would not be, in CHPA's view, an appropriate science-based approach.

Defining a nanomaterial as a structure between 1 and 100 nm, and using this definition to establish new regulations on products containing nano-sized materials, would, they asserted,  erroneously group drug products together to form a new category based on size of ingredients.  Nanotechnology is not a separate drug category, but a technology used to, among other things, generate nanometer-sized ingredients and excipients. Inclusion of nanometer-sized active ingredients or excipients in a drug product does not by itself determine a product's safety and efficacy (i.e. size alone is not itself an indicator of toxicity). 

CHPA agreed that the agency should distinguish between engineered nanomaterials and those
naturally occurring at the nanoscale.  There exist common pharmaceutical ingredients with a long history of use that should not be considered as "engineered nanomaterials" or as agglomerates of nanomaterials but which may have particles whose size naturally falls within this range.

CHPA also noted that NIOSH accurately refers to nanotechnology as the manipulation of matter on a near-atomic scale to produce new structures, materials, and devices.  Nanomaterials are mainly engineered for their novel chemical, physical, and quantum mechanical properties; at the nanometer size, many materials exhibit such unique beneficial properties that may not exist when at the micron size. CHPA argued it is appropriate to include in the description the notion of particles that are deliberately manipulated and controlled at the nanoscale, which also exhibit changes in physical, chemical, or electromagnetic properties, the existence of unique phenomena to enable novel applications.

For example, milling, a beneficial process for the manufacturing of many individual pharmaceutical ingredients, may create particles with a portion of the particle size distribution under 1 micron; however, the chemical properties of the milled ingredient usually do not differ drastically from that of the bulk ingredient.

The agency should give further consideration, said CHPA,  to the possibility that not all materials should be considered equal; each material must be evaluated on a case-by-case basis. For example, soluble nanomaterials might not be treated the same as insoluble ones.  

FDA Releases Draft Guidance on Nanotechnology

The U.S. Food and Drug Administration last week released draft guidance designed to move the process forward of providing its regulated industries with greater certainty about the use of nanotechnology (which generally involves materials made up of particles that are one billionth of a meter in size). The guidance outlines the agency’s current view on certain issues about regulated products that contain nanomaterials or involve the application of nanotechnology.

FDA has not to date established regulatory definitions of “nanotechnology,” “nanoscale” or related terms. The term is perhaps most commonly used to refer to the engineering (i.e., deliberate manipulation, manufacture or selection) of materials that have at least one dimension in the size range of approximately 1 to 100 nanometers. For example, theNational Nanotechnology Initiative Program defines nanotechnology as the understanding and control of matter at dimensions between approximately 1 and 100 nanometers, where unique phenomena enable novel applications. Other factors such as function, shape, charge, the ratio of surface area to volume, or other physical or chemical properties have also been mentioned in various published definitions.

Our readers know that nanotechnology, the science involving manipulation of materials on an atomic or molecular scale, is an emerging technology with a broad range of potential applications, such as increasing bio-availability of a drug, improving food packaging, and in cosmetics.

The draft guidance document, “Considering Whether an FDA-Regulated Product Involves the Application of Nanotechnology,” represents a first step toward providing some regulatory clarity on the FDA’s approach to nanotechnology. Specifically, the agency named certain characteristics – such as the size of nanomaterials used and the exhibited properties of those materials – that may be considered when attempting to identify applications of nanotechnology in regulated products.

For products subject to premarket review, the FDA intends to apply the points contained in the draft guidance, when finalized, to better understand the properties and behavior of engineered nanomaterials. For products not subject to premarket review, the FDA will urge manufacturers to consult with the agency early in the product development process so questions related to the regulatory status, safety, effectiveness, or public health impact of these products can be adequately addressed.

In 2006, the FDA formed the Nanotechnology Task Force, charged with identifying and addressing ways to better enable the agency to evaluate possible adverse health effects from FDA-regulated nanotechnology products.  The agency issued a report by the task force in 2007 that recommended that the FDA issue additional guidance and take steps to address the potential risks and benefits of drugs, medical devices and other FDA-regulated products using nanotechnology.

 

Nanotechnology Legislation Introduced in Senate

Two Democratic legislators have introduced a bill that would create an FDA program to assess the potential health and safety effects of nano-technology ingredients in various consumer products.  Sens. Mark Pryor (D-Ark.) and Benjamin L. Cardin (D-Md.) introduced the "Nanotechnology Safety Act of 2010," S. 2942, last week. Their introductory remarks here.

The FDA established a Nanotechnology Task Force, which issued a report in July 2007. In the task force report, recommendations were made regarding FDA’s future direction for regulating nanomaterial-containing products. Guidance development was included as one the recommendations. The FDA’s Advisory Committee for Pharmaceutical Science and Clinical Pharmacology met In 2008. Among the agenda topics was a discussion of issues pertaining to the use of nanotechnology in drug manufacturing, drug delivery, or drug products.  Later, FDA held a public meeting to gather information that will assist the agency in further implementing the recommendations of the Nanotechnology Task Force Report relating to the development of agency guidance documents concerning nanotechnology.

The bill would create a program for the scientific investigation of nanoscale materials included or intended for inclusion in FDA-regulated products, to address the potential toxicology of such materials, the effects of such materials on biological systems, and interaction of such materials with biological systems.  Specifically, FDA would be charged to assess scientific literature and data on general nanoscale material interactions with biological systems and on specific nanoscale materials of concern to Food and Drug Administration, and collect, synthesize, interpret, and disseminate scientific information and data related to the interactions of nanoscale materials with biological systems.

Nanotechnology applications in drug development are likely to have a significant impact on the products that FDA regulates. Products containing nanomaterials are being investigated for potential applications as therapeutics, and some products containing nanoscale materials are already on the market. While some of these nanomaterials are nanoscale versions of larger materials used in approved products, other nanomaterials are novel and have never been used in drug products. In 2009, the FDA introduced the "Nanotechnology Initiative", a collaborative effort between FDA and the Alliance for NanoHealth.

The proposed law would also require a report from FDA by 2012 that includes a review of the coordination of activities under the program with other departments and agencies participating in the National Nanotechnology Initiative. The bill would send $25 million annual funding to the agency for the program. The bill was referred to the Committee on Health, Education, Labor, and Pensions,

Many readers of MassTortDefense know that nanotechnology refers to a new field of technology that seeks to manipulate and control products, really matter, on the atomic and molecular scale, typically 100 nanometers or smaller. To give some sense of scale, one nanometer is one billionth, or 10-9 of a meter. A nanometer compared to a meter is the roughly the same ratio as that of a baseball to the size of the Earth. Or another analogy, a nanometer is the length a man's whiskers grow in the time it takes him to lift his razor to his face to shave. We have posted on this topic here, here, and here.
 

EU Council Adopts Regulations for Cosmetics with Nano-ingredients

We have posted about nanotechnology issues before. Readers following nano-issues will want to note that the Council of the European Union last week approved an updated set of regulations on cosmetic products, and they include a requirement that cosmetics containing nanoscale ingredients have that information on their labels. [In the European Union, regulations automatically apply to all  member states, while directives are implemented through national legislation. The regulation thus represents a common European code on cosmetic products, designed to reduce the uncertainties arising from a differentiated implementation of the previous directives in the 27 member states.]

Specifically, the regulation states that, “All ingredients present in the form of nanomaterials shall be clearly indicated in the list of ingredients. The names of such ingredients shall be followed by the word ‘nano’ in brackets.”  see p. 61.  Some observers have questioned whether the mention of the term "nano" in labels will offer consumers much meaningful guidance. The FDA's 2007 Nanotechnology Task Force Report did not recommend labeling because current science did not support a finding that products with nanoscale materials necessarily present greater safety concerns than those without nanoscale materials.

The document indicates that the use of nanomaterials in cosmetic products may increase with the further development of technology. In addition, the EU Council suggest that in order to ensure a high level of consumer protection, free movement of goods, and legal certainty for manufacturers, it is necessary to develop a uniform definition for nanomaterials at the international level.  In the interim, "nanomaterial" for regulatory purposes means an insoluble or biopersistant and intentionally manufactured material with one or more external dimensions, or an internal structure, on the scale from 1 to 100 nm.

The Council states that, at present, there is inadequate information on the risks associated with nanomaterials. In order to better assess their safety, the Council calls for cooperation with relevant bodies on test methodologies which take into account specific characteristics of nanomaterials.

The new rule also will require manufacturers of new cosmetic products containing nanomaterials to notify the European Commission and to provide certain toxicological information before the products are placed on the market. Published reports suggest that manufacturers may have up to 3 years to comply with the new label regulations.

 

Early Alert for Nanotechnology Conference

Readers interested in nanotechnology issues may be interested in the Second NanoImpactNet Conference on the future with nanotechnology.  It is to be held in Lausanne, Switzerland, March 9-12, 2010.

Information on the preliminary program is available here.

And information on abstract submission and registration for the conference is available here.

The conference is organized by NanoImpactNet, a European network on the health and environmental impact of nanomaterials, including academic and government laboratories
working on nano-toxicology and nano-ecotoxicology. 

EPA Finalizes Nano-technology Research Strategy

Many readers of MassTortDefense have wondered about the potential future litigation risks associated with nanotechnology. The U.S. Environmental Protection Agency has just finalized its new strategy to guide its research into how nanomaterials, used in a growing number of consumer products, might be studied for potential effects on human health and the environment. The Nanomaterial Research Strategy (NRS) describes the EPA's strategy for conducting and supporting research to understand the potential human health and ecological implications from exposure to manufactured nanomaterials, and how nanotechnology can be used sustainably in environmental protection applications.

EPA has written this document with three stated purposes:
(1) to guide its own researchers and managers as they conduct EPA’s research program,

(2) to assist scientists in other organizations and agencies as they plan research programs, and

(3) to inform the public of how EPA intends to generate scientific information to guide environmental decisions related to nanomaterials.

With the use of nanotechnology in the consumer and industrial sectors expected to increase
significantly in the future, nanotechnology offers society the promise of major benefits. The challenge for environmental protection is to ensure that, as nanomaterials are developed and used, unintended consequences of exposures to humans and ecosystems are prevented or minimized. In addition, knowledge concerning how to sustainably apply nanotechnology to detect, monitor, prevent, control, and clean up pollution is needed, says the NRS.

The strategy builds on the work of the Nanotechnology Environmental and Health Implications
Working Group (NSTC, 2008), and in the EPA’s Nanotechnology White Paper (EPA, 2007).

EPA’s strategy focuses on four areas:

􀂃 Identifying sources, fate, transport, and exposure
􀂃 Understanding human health and ecological effects to inform risk assessments and test methods
􀂃 Developing risk assessment approaches
􀂃 Preventing and mitigating risks
 

The key science questions described in the strategy document are intended to help decision makers answer the following questions:
􀂃 What nanomaterials, in what forms, are most likely to result in environmental exposure?
􀂃 What particular nanomaterial properties may raise toxicity concerns?
􀂃 Are nanomaterials with these properties likely to be present in environmental media or biological
systems at concentrations of concern, and what does this mean for risk?
􀂃 If we think that the answer to the previous question is “yes,” can we change properties or mitigate
exposure?

Readers of MassTortDefense know that nanotechnology is the process of manipulating materials 1 million times smaller than a millimeter. Nanomaterials, lighter and stronger than other materials, are used in hundreds of products already on the market, including many cosmetics and skin care products.  We have posted on this topic before.  Materials can take on new properties at the nano level, becoming stronger, better conductors of heat or electricity, for example.

The EPA's own office of research development is focusing its research on seven manufactured nanomaterial types: single-walled carbon nanotubes, multiwalled carbon nanotubes, fullerenes, cerium oxide, sliver, titanium dioxide and zero-valent iron. Carbon nanotubes are used in vehicles, sports equipment and electronics, while titanium dioxide is used in paints, cosmetics and sunscreens, as reported by EPA.  The Agency is also part of the government-wide National Nanotechnology Initiative.

Nano-particle Study Generates More Heat Than Light

A new study published in the European Respiratory Journal is generating media attention, and some observers assert it may have far-reaching implications for the nano-tech industry. Is this warranted?

In this study, Song, et al., Exposure to nano-particles is related to pleural effusion, pulmonary fibrosis and granuloma, 34(3) Eur. Respir. J. 559-567 (2009), researchers at China's Capital University of Medical Sciences linked lung disease in seven Chinese workers, two of whom reportedly died, to nano-particle exposures in a print plant where a paste containing nano-particles was sprayed onto a polystyrene substrate, with subsequent heat-curing.

The study reported that seven young female workers (ages 18–47), exposed to nano-particles for 5–13 months, were admitted to the hospital, all with shortness of breath and pleural effusions. Polyacrylate, consisting of nano-particles, was confirmed in the workplace. Pathological examinations of the patients' lung tissue displayed non-specific pulmonary inflammation, pulmonary fibrosis, and foreign-body granulomas of pleura. By transmission electron microscopy, nano-particles were observed to have lodged in the cytoplasm and caryoplasm of pulmonary epithelial and mesothelial cells, but also were located in the chest fluid.

The authors expressed concern that long-term exposure to some nano-particles may be related to serious damage to human lungs.  But, putting the media reception aside, this study appears to do more to highlight the common sense need to follow good industrial hygiene practices than to provide compelling evidence of any unique health risks posed by engineered nano-particles. The plant sprayed a strong chemical paste and then heated plastic material in an enclosed space apparently lacking ventilation.  The room in which the women worked was small and unventilated for a significant part of their exposure period. Only on occasion, they wore mere "cotton gauze masks." 

From the study it appears that the workers had a complicated exposure history to a mix of chemicals; while there was a reported association of nano-particles with lung disease, it is unclear which, if any, of the chemical exposures might have contributed to the lung issues. Readers of MassTortDefense know that an association is not causation.  For example, formation of thermodegradation fume products are known to cause significant occupational disease, and paint spraying has been shown to be potentially harmful long before nano-sizing of chemicals was utilized. 

Moreover, sufficient exposure information necessary to even begin to think about a causal connection between exposure to nano-sized particles in the paste/dust and lung and heart disease in the workers was missing.  Clearly, there may be alternative explanations for what the study authors described finding in the patients.

As noted here before, NIOSH emphasizes the use of a variety of engineering control techniques, implementation of a risk management program in workplaces where exposure to nanomaterials exists, and use of good work practices to help to minimize worker exposures to nanomaterials.
 

 

 

Investor Report Questions Reporting About Nano-Risks

New and more extensive government regulation may be in the future for a host of industries and products we have blogged about at MassTortDefense, including tobacco, medical devices, food, and drugs.  A new report from the "Investor Environmental Health Network" calls for regulations not of the products themselves, but new rules governing disclosure of potential liabilities that can arise from emerging product technologies like nanotechnology.

EHN is a partnership of investment managers who report they oversee more than $25 billion in assets. The new report identifies alleged "loopholes" in the current system of securities and accounting regulation that the group says prevent a complete reporting of a firm's potential liabilities. They point, as a case study, to the alleged danger of asbestos-like litigation risks for nanotechnology companies and investors, as potentially "ultra-hazardous" nanotechnologies enter the market.

They argue that nanomaterials, lighter and stronger than other materials, are used in hundreds of products already on the market, including many cosmetics and skin care products. They cite a  study published in May, 2008 which suggested certain carbon nanotubes could have similar health effects as asbestos; and they point to a concern that particles at the nano level will be able to penetrate membranes in the brain in a way traditional particles do not.  Materials can take on new properties at the nano level, becoming stronger, or better conductors of heat or electricity, for example. But what creates their potential for new applications across a range of industries, may also be the source of their risk. 

The report calls for more consistent liability estimates made to insurers and investors; benchmarking liabilities against other companies whose published litigation results could offer another estimate of liability; and several new disclosure regulations from the SEC.

Companies developing or contemplating selling products with nanotechnology will, of course, want to monitor these efforts, which seem at times to call for a level of foresight requiring a working crystal ball. This particular report appears to assume that all the potential risks of nanotechnology are real; that manufacturers have no interest in exploring the potential risks; and, if they do, certainly won't ever disclose them.  Begrudgingly, it admits that "a number of questions remain regarding whether carbon nanotubes will actually cause health harms to the same degree that asbestos did."  That's an understatement.  In fact, the published studies relate to only some forms of carbon nanotubes, and like any potentially toxic substance, the levels of exposure to carbon nanotubes by workers or consumers is a key issue in assessing risk.  Many of the current uses of nanotechnology are in FDA-regulated products where there is a demonstrated lack of dermal absorption. Similarly, regarding potential nanotechnology in food packaging, substances used in food packaging are already regulated by FDA as “food contact substances” with the burden resting on the sponsor of a new food contact substance to demonstrate its safety.

Currently, companies involved in nanotechnology regularly disclose to investors that there is no scientific agreement on the health effects of nanomaterials; they note that some scientists believe that in some exposure contexts, nanomaterials may be hazardous to an individual’s health or the environment. They disclose that the science of nanotechnology is based on arranging atoms in way not made in nature; that future research into the effects of nanomaterials may thus have an adverse effect on products using the new technology.  They also typically disclose that the future regulation and limitation of the kinds of materials used in or used to develop nanotechnology-based products could halt or delay the commercialization such products. Such disclosures would seem to put investors on adequate notice of an uncertain future; speculative and alarmist predictions of the "next asbestos" seem unwarranted.

New Report from Project on Emerging Nanotechnologies

A new report from the Project on Emerging Nanotechnologies argues that existing health and safety agencies are unable to cope with the risk assessment, standard setting, and oversight challenges of advancing nanotechnology. The new report, Oversight of Next Generation Nanotechnology, says the nation needs a new agency to deal with the health and environmental impacts of these technically complex products promised by rapid 21st century scientific advances.

Nanotechnology involves working at the scale of single atoms and molecules. The U.S. government defines nanotechnology as “the way discoveries made at the nanoscale are put to work.” The nanoscale is roughly 1–100 nanometers. There are 25.4 million nanometers in an inch and 10 million nanometers in a centimeter.

Nanoscale materials often behave differently than materials with a larger structure do, even when the basic material (e.g., silver or carbon) is the same. Nanomaterials can have different chemical, physical, electrical, and biological characteristics. For example, an aluminum can is perfectly safe, but nano-sized aluminum is explosive.

The novel characteristics of nanomaterials mean that risk assessments developed for ordinary materials may be of limited use in determining the health and environmental risks (and thus product liability and mass tort risks) of the products of nanotechnology. A body of literature speculates about the potential for unusual health and environmental risks given that nanometer-scale particles can get to places in the environment and the human body that are inaccessible to larger particles. Nanomaterials have a much larger ratio of surface area to mass than ordinary materials do. It is at the surface of materials that biological and chemical reactions take place, and so some expect nanomaterials to be more reactive than bulk materials.

The report explains that almost all the current applications of nano are “passive,” in that they involve adding a nanomaterial to an ordinary material as a way of improving performance. For example, adding carbon nanotubes to rubber can greatly increase the toughness of the rubber without reducing its flexibility. Passive nanotechnology applications thus include using materials like carbon nanotubes, silver nanoparticles and porous nanomaterials to add functionality to products by nature of their physical and chemical form, rather than by how they respond to their environment.

Second generation, "active" nanostructures, typically involve nanometer-scale structures that change their behavior in response to changes in their environment. These changes might come about as a result of a mechanical force, a magnetic field, exposure to light, the presence of certain biological molecules or a host of other factors.

A good deal of research, involving a variety of different nanotechnologies, is being devoted to cancer detection and cure. One of the main goals of using nanotechnology for medical purposes, observes the report, is to create devices that can function inside the body and serve as drug delivery systems with specific targets. Another hot area: researchers are exploring the use of nanomaterials and nanotechnology techniques to vastly improve computers.

Even the first-generation nanotechnologies challenge traditional risk assessment methods, argues the report. Multiple characteristics contribute to the potential toxicity of many nanomaterials; they include not just mass or number of particles but also the shape of the particles, the electrical charge at the particle surface, the coating of the particle with another material and numerous other characteristics. Science has yet to determine which of these characteristics are most important under what circumstances.

After describing the current regulatory regime, the paper calls for a more unitary regulatory approach, including a new Department of Environmental and Consumer Protection to oversee product regulation, pollution control and monitoring, and technology assessment.
 

FDA Introduces Nanotechnology Initiative

Last week the FDA introduced the "Nanotechnology Initiative", a collaborative effort between FDA and the Alliance for NanoHealth (ANH) and its eight member institutions. The alliance's eight academic institutions are the Baylor College of Medicine, the University of Texas' M.D. Anderson Cancer Center, Rice University, the University of Houston, the University of Texas Health Science Center at Houston, Texas A & M Health Science Center, the University of Texas Medical Branch at Galveston and the Methodist Hospital Research Institute in Houston.


The initiative is designed to push for the development of safe and effective implementation of nanotechnology into medical products. Under a Memorandum of Understanding, the FDA/ANH Nanotechnology Initiative will work to expand knowledge of how nanoparticles behave and affect biologic systems, and to facilitate the development of tests and processes that might mitigate the risks associated with nanoengineered products. The nanotechnology initiative with the Alliance for NanoHealth is an effort to engage resources and technical expertise in this rapidly advancing field.

FDA recognizes that nanotechnology holds great promise for the advancement of novel medical products. All outcomes from this public-private partnership will be placed in the public domain.
Readers of MassTortDefense know that nanotechnology involves the creation and use of materials at the level of molecules and atoms; it presents opportunities but also challenges for the FDA's entire regulatory product jurisdiction, from food to medical devices to therapeutics. Products from the new technology may also present product liability issues for manufacturers.

New NIOSH Report On Nano-technology

Updating their previous draft report from July 2006, NIOSH is about to produce a final report to provide an overview of what is known about the potential hazards of nanoparticles and how workplace exposure to nanoparticles can be minimized and monitored.

Nanotechnology—the manipulation of matter on a near-atomic scale to produce new structures,
materials, and devices—offers the promise of unprecedented scientific advancement for many sectors, such as medicine, consumer products, energy, materials, and manufacturing. Nanotechnology has the power not only to improve existing technologies, but to dramatically enhance the effectiveness of new applications. Research on the potential applications of nanotechnology continues to expand rapidly worldwide. New nanotechnology consumer products emerge at a rate of three to four per week. Over the course of the next decade, nanotechnology could have a $1 trillion impact on the global economy and employ two million workers—half of them residing in the U.S. While nanomaterials present seemingly limitless possibilities, they bring with them new challenges to understanding, predicting, and managing potential safety and health risks.

The report analyzes several animal and epidemiologic studies, hypothesizing that effects of inhaled nanoparticles are similar to ultrafine particles with similar characteristics or may be predicted by surface area, composition, and particle number. Noting the potential for chronic respiratory effects such as inflammation and tumor development, NIOSH emphasizes that exposure assessment should be conducted for environments where nanomaterials are manufactured or used as part of a manufacturing process. They recommend several methods for measuring and characterizing nanomaterial air concentrations including aerosol sampling, airborne surface area analysis, and particle number measurement.

The NIOSH report notes several challenges for implementation of successful nanoparticle monitoring strategies, including lack of current standards and complexity/uniqueness of individual nanoparticle types. Because health risk information and monitoring strategies are limited at this time, they emphasize use of a variety of engineering control techniques, implementation of a risk management program in workplaces where exposure to nanomaterials exists, and use of good work practices to help to minimize worker exposures to nanomaterials.

Two Nano-Technology Support Bills Introduced in House

Rep. Michael Honda (D-Calif.) has introduced legislation that he says will promote the development and responsible stewardship of nanotechnology. His bill, the Nanotechnology Advancement and New Opportunities (NANO) Act (H.R. 820), would expand the federal government's efforts to support the commercialization of products emerging from nanotechnology research. A somewhat similar bill was introduced last month by Rep. Bart Gordon (D-Tenn.), chairman of the House Science and Technology Committee. That bill, the National Nanotechnology Initiative Amendments Act of 2009 (H.R. 554) has 21 co-sponsors so far. The S&T Committee has made ensuring that the U.S. is a leader in the development of nanotechnology a priority for the new Congress.

Gordon's bill aims to reauthorize the multi-agency National Nanotechnology Initiative that Congress formally established in 2003 through the 21st Century Nanotechnology Research and Development Act of 2003. A National Nanotechnology Coordination Office along with the National Research Council of the National Academy of Sciences would supervise a national nanotechnology program. 

While the two bills have much in common, H.R. 820 includes elements like the offering of tax credits for individuals purchasing stock in certain types of nanotechnology firms, such as small or start-up companies. Honda reports that H.R. 820 draws on the work of a Task Force on Nanotechnology that he convened in 2005. That task force highlighted various ways the U.S. government could promote the commercialization of nanotechnology, as other governments already are doing. Accordingly, the NANO Act would authorize up to $100,000 to establish public-private partnerships to advance the commercialization of nano-manufacturing technologies to address critical scientific and engineering needs of national importance.

Gordon's bill, H.R. 554, would encourage nanotechnology research to provide solutions to important problems in such areas as nanoelectronics, energy efficiency, health care, and water remediation and purification. Both bills use various means to support the training of students in nanotechnology to ensure a future workforce.
 

Nanotechnology Resources

MassTortDefense has posted on nanotechnology issues before.  In the past few months, the EPA has clarified its view of carbon nanotubes, 73 Fed. reg. 64946 (Oct. 31, 2008); has issued a new rule affecting 50 or more nanoparticles in use in industry, 73 Fed.Reg. 65743 (Nov.5, 2008); and has asked for public comment on a petition for rulemaking submitted concerning nanoscale silver. 73 Fed.Reg. 69644 (Nov.19, 2008).

These actions may be a precursor of a flood of government actions affecting nanotechnology by a new Administration.  Here are some links to help interested readers stay on top of these issues (no endorsement of content, as usual):

Centers for Disease Control and Prevention / NIOSH
U.S. Environmental Protection Agency
U.S. Food and Drug Administration
National Nanotechnology Initiative (NNI)
Dept. of Health and Human Services National Toxicology Program

Woodrow Wilson Center, Project on Emerging Nanotechnologies

International Council on Nanotechnology (ICON), Environmental, Health and Safety database: Nano Science and Technology Institute (NSTI)

NanoBusiness Alliance

European Commission
Cluster Science, including Nanoclusters and Nanoparticles
Virtual Journal of Nanoscience and Nanotechnology
NanoScience Today Imagazine  

Nano-technology Conference Set for March, 2009

Those interested in nano-technology issues may want to check out a conference next Spring, entitled NanoImpactNet: For a Healthy Environment in a Future with Nanotechnology.

NanoImpactNet is the European network on the health and environmental impact of  nanomaterials. It is a platform for exchange about research ideas and to bring together scientists, industry, policy makers and consumers to ensure the safe and responsible development of nanomaterials. NanoImpactNet is part of the European Commission’s commitment to define a robust European strategy on nanotechnology which includes health, safety and environmental issues.

Launched in April 2008, this multidisciplinary network’s objective is to create a scientific basis to support the definition of regulatory measures and the implementation of legislation across the EU.  The 24 institutes behind NanoImpactNet members are leading European research groups active in the fields of nanosafety, nanorisk assessment and nanotoxicology. Through numerous workshops over a period of four years, NanoImpactNet will bring together some of the top researchers to discuss future strategies, to exchange their ideas with the different stakeholder groups and to further the responsible development of nanotechnology.
 

The conference is set for Laussanne, Switzerland, March 23-27, 2009.
 

New Report From National Research Council On Nanotechnology

A new report from the National Research Council questions the government's current plan for research on the possible health and environmental risks posed by nanomaterials, which are increasingly being used in consumer products and other industry. The report emphasizes the need for an effective national plan for identifying and managing potential risks, a step seen as essential to the successful development and public acceptance of nanotechnology-enabled products.

Nanoscale engineering manipulates materials at the molecular and atomic level to create structures with unique and useful properties – materials that are both very strong and very light, for example. More than 600 products involving nanomaterials are already on the market, the majority of them health and fitness products, such as skin care and cosmetics. And over the next decade, nanomaterials will be used increasingly in products ranging from medical therapies to food additives to electronics. MassTortDefense has posted about nano-issues before.

Growing use of nanomaterials means that more workers and consumers may be exposed to them, and uncertainties remain in the minds of some about their health and environmental effects; while nanomaterials can yield tremendous, special utility, they may also have possibly toxic risk properties.

The National Nanotechnology Initiative, which coordinates federal agency investments in nanoscale R&D, developed a research plan to investigate these risks, and the office that oversees NNI asked the National Research Council to review the plan.  (The NRC report was sponsored by the National Nanotechnology Coordination Office. The National Academy of Sciences, National Academy of Engineering, Institute of Medicine, and National Research Council make up the National Academies. They are private, nonprofit institutions that provide science, technology, and health policy advice under a congressional charter.)  The Research Council is the principal operating agency of the National Academy of Sciences and the National Academy of Engineering.

The committee report did not focus on current uses of nanomaterials and any potential risks to the public. Rather, the report focused on what would constitute an effective national research strategy for ensuring that current and future uses of nanomaterials are without significant impacts on human health or the environment.

The current plan, involving nano-risk research across several federal agencies, lacks an overarching research strategy needed to gain public acceptance and realize the promise of nanotechnology, according to the report.  NNI's plan identifies broad research categories for assessing health and environmental risks, and many of the research needs listed within these categories will aid risk assessment, the report says. But the plan fails to identify some important other areas that should be investigated; for example, "Nanomaterials and Human Health" should include a more comprehensive evaluation of how nanomaterials are absorbed and metabolized by the body and how toxic they are at realistic exposure levels. Furthermore, the current research plan, according to the report, does not provide a clear picture of the current understanding of these risks or where it should be in 10 years. And though the research needs listed in the plan are valuable, the NRC committee thinks they are incomplete, in some cases missing elements crucial for progress in understanding nanomaterials' health and safety impacts.

In its assessment of gaps in existing research, the current NNI plan overstates the degree to which already funded studies are meeting the need for research on health and environmental risks, the report says. For example, more than half of the currently funded projects on nanotechnology and human health are aimed at developing therapies for diseases. While this research is important, it will not shed light on health risks that may be posed by nanomaterials. Moreover, the plan does not note the current lack of studies on how to manage consumer and environmental risks, such as how to manage accidents and spills or mitigate exposure through consumer products.

A truly robust national strategic plan would involve a broader group of stakeholders, and would consider the untapped knowledge of nongovernment researchers and academics, the committee said. The current structure of NNI would make developing a new strategy difficult, says the report. NNI should continue to foster successful interagency coordination, with the aim of ensuring that the federal research strategy on the health and safety impacts of nanotechnology is an integral part of the broader national strategic plan.
 

Nanotechnology Update

Many readers of MassTortDefense know that nanotechnology refers to a new field of technology that seeks to manipulate and control products, really matter, on the atomic and molecular scale, typically 100 nanometers or smaller. To give some sense of scale, one nanometer is one billionth, or 10-9 of a meter. A nanometer compared to a meter is the roughly the same ratio as that of a baseball to the size of the Earth. Or another analogy, a nanometer is the length a man's whiskers grow in the time it takes him to lift his razor to his face to shave.

First, the European Food Safety Authority (EFSA) recently called for public comments on its draft scientific opinion document assessing the potential risks of engineered nanomaterials used in food and feed. EFSA opinions provide guidance for the European Commission and European Union member state food safety organizations.

EFSA has noted that complete information about engineered nanomaterials in food is lacking, leading to uncertainties in risk assessment. In particular, the agency said knowledge is limited about how engineered nanomaterials in food should be characterized, detected, and measured. It also said more information is needed on the toxicological and environmental impacts of using such nanomaterials.

The comment period on the draft opinion is open until Dec. 1, after which the scientific opinion will be revised and finalized, taking the comments into account.

Second, back in the US, the activist group Consumers Union released new product tests this week, claiming to show that some sunscreens claiming not to contain nanoparticles appeared to contain them.
 
The group is concerned because nano-size particles are known in some applications to have different properties than the conventional versions of these chemicals. Sunscreen manufacturers use nano-size particles of these ingredients for several reason, including because they help make the products clear rather than opaque, something consumers prefer. The European Union has required manufacturers to submit data on sunscreens containing nanoparticles.

Third, the EPA has issued an announcement intended to give notice of the potential application of the Toxic Substances Control Act (TSCA) requirements to carbon nanotubes (CNTs). Carbon nanotubes are generally made from sheets of graphite no thicker than an atom—about a nanometer, or one billionth of a meter wide—and formed into cylinders, with the diameter varying from a few nanometers up to tens of nanometers. They are excellent conductors of electricity. Carbon nanotubes can also be used to reinforce polymers to create very strong plastics. Carbon nanotubes show promise as building blocks for computer chips that are smaller and faster than those made of silicon. Economists predict that the market for carbon nanotubes will grow to more than $1 billion by 2014.

EPA generally considers CNTs to be chemical substances distinct from graphite or other allotropes of carbon already listed on the TSCA Inventory. Many CNTs may therefore be new chemicals under TSCA. If a particular CNT is not on the TSCA Inventory, anyone who intends to manufacture or import that CNT is required to submit a premanufacture notice (PMN) at least 90 days before commencing manufacture. MassTortDefense has posted about carbon nanotubes before.

Apparently, inquiries to the Agency and questions in public forums indicated a lack of clarity on this issue. Some of the misunderstanding may be the result of an EPA communication to a chemical manufacturer a number of years ago pertaining to a substance the Agency now considers to be a carbon nanotube material. EPA understands that the earlier communication may have been misunderstood by some companies as a possible indication that all CNTs may be equivalent to other allotropes of carbon already on the TSCA Inventory. Hence the clarification.
 

FDA Meeting On Nano-Technology Spurs Debate

The FDA held a public meeting on September 8, 2008, to gather information that will assist the agency in further implementing the recommendations of the Nanotechnology Task Force Report relating to the development of agency guidance documents concerning nanotechnology. In July 2007, FDA had issued a report analyzing scientific and regulatory considerations relating to the safety and effectiveness of FDA-regulated products containing nanoscale materials regulated by FDA, and making recommendations regarding these considerations. The Nanotechnology Task Force Report made recommendations which covered foods (including dietary supplements), food and color additives (including food contact substances), animal drugs and feeds, cosmetics, human drugs and biologics, and medical devices. Additionally, the Report summarized the state of the science for biological interactions with nanoscale materials.

The meeting included a plenary session led by Dr. Norris Alderson, head of the FDA Nanotechnology Task Force, followed by separate sessions for prescription and OTC drugs, cosmetics, medical devices, food additives, and others. FDA speakers reportedly were interested in comments on the circumstances under which the regulatory status of a product might change if nanoscale materials were utilized instead of the traditionally sized materials evaluated by regulatory officials when the product was first approved. 

Andrew Maynard, the chief science adviser for the Project on Emerging Nanotechnologies, told the FDA at the September meeting that they should view products containing nanomaterials as potentially "risk-added." Maynard said that materials with a dimension less than 100 nanometers exhibit unique properties due to their small size, and thus are “value-added." But, Maynard said, the unique properties exhibited by nanomaterials might also carry special risks. Francis Quinn, speaking on behalf of the Personal Care Products Council, offered a different perspective. For example, while nanoparticles are used in the early stages of developing sunscreens, by the time they are mixed with other ingredients they are no longer nanoscale and present no different risks than traditional sunscreens. Jay Ansell, senior director of the council, said no special labeling of nanoscale ingredients in cosmetics is needed.

But other speakers said the FDA needs to take a different approach as it contemplates regulating products containing nanoscale ingredients. The Conservation Law Foundation said that existing frameworks for assessing risks need to be updated to address nano-specific attributes such as particle characteristics. And a researcher from The George Washington University urged caution about the use of nanomaterials in dietary supplements.


As an aside, the latest report from the Project on Emerging Nanotechnologies addresses nano-scale silver. Silver Nanotechnologies and the Environment: Old Problems or New Challenges. The most common nanotechnology material currently used in the products is silver, which is mentioned in 235 product descriptions, such as silver-containing socks, baby carriages, air filters, coin-operated washing machines, and swimming pool treatments. 

The report asserts that widespread use of nanoscale silver will challenge regulatory agencies to balance important potential benefits against the possibility of significant environmental risk, highlighting the need to identify research priorities concerning this emerging technology. The issue of assessing the risks posed by nanoscale silver was highlighted after the Environmental Protection Agency’s (EPA) San Francisco office earlier this year imposed a fine of $200,000 on a California company selling computer keyboards and mouses coated with nanosilver. EPA issued the fine on the basis that the products should have been registered under federal pesticide law because of the company’s germ-killing claims. Due to its antibacterial properties, some have argued that the Federal Insecticide, Fungicide, and Rodenticide Act may be used to regulate many uses of nanoscale silver.

Nanosilver is a new challenge, says the report, a problem that fits poorly into the old boxes of the existing regulatory system. EPA is crafting a Federal Register notice that will invite comment on a citizen’s petition on nanoscale silver. EPA also has a 2007 white paper on nanotechnology.
 

FDA To Hold Public Meeting On Nanotechnology

The FDA will hold a public meeting on September 8, 2008, to gather information that will assist the agency in further implementing the recommendations of the Nanotechnology Task Force Report relating to the development of agency guidance documents concerning nanotechnology. The primary purpose of the meeting is to determine what factors the agency should consider in providing guidance on:

1) The information and data that may be needed to demonstrate the safety and effectiveness of FDA-regulated products containing nanoscale materials; and

2) The circumstances under which a product’s regulatory status might change due to the presence or use of nanoscale materials.

Nanotechnology allows scientists to work on the scale of molecules to create, explore, and manipulate materials measured in nanometers; billionths of a meter. MassTortDefense has posted on nano-issues here and here.

In July 2007, FDA issued a report analyzing scientific and regulatory considerations relating to the safety and effectiveness of FDA-regulated products containing nanoscale materials regulated by FDA, and making recommendations regarding these considerations. The Nanotechnology Task Force Report made recommendations which covered foods (including dietary supplements), food and color additives (including food contact substances), animal drugs and feeds, cosmetics, human drugs and biologics, and medical devices. Additionally, the Report summarized the state of the science for biological interactions with nanoscale materials.

In addition, FDA is working with the National Institutes of Health (particularly the NanoHealth Enterprise) to explore methods for receiving and sharing data relating to, for example, general product development, including research on failed product candidates, and biological interactions of certain characteristics of nanoscale materials.

The meeting will begin with a plenary session at which FDA will review the goals of the meeting and give a general overview of the analysis and findings of the Nanotechnology Task Force and agency activities since publication of the Report in July 2007. Following will be breakout sessions on medical devices, including diagnostics; prescription drugs, including
biological drugs, animal drugs and OTC drugs, including sunscreens; food and color additives, including food contact substances; dietary supplements; and cosmetics.
 

Think Tank Releases Nano-Technology Report

A Washington, DC think tank last week released a new report with suggestions on how the next administration should approach regulation of nano-technology in products.  The Project on Emerging Technologies is based at the Woodrow Wilson Center in Washington. The Project was established in 2005 as a partnership between the Woodrow Wilson International Center for Scholars and the Pew Charitable Trusts. The Project is dedicated to helping ensure that as nanotechnologies advance, possible risks are minimized, public and consumer engagement remains strong, and the potential benefits of these new technologies are realized.

Nanotechnologies are hailed by many as the next industrial revolution. They promise to change everything from the cars we drive to the clothes we wear, from the medical treatments our doctors can offer to our energy sources and workplaces. Although focused on very small particles, nanotechnologies offer large potential benefits. From new cancer therapies to pollution-eating compounds, from more durable consumer products to detectors for bio-hazards like anthrax, from novel foods to more efficient solar cells, nanotechnologies are changing the way people think about the future.

The Project on Emerging Nanotechnologies collaborates with researchers, government, industry, NGOs, policymakers, and others to look long term, to identify gaps in knowledge and regulatory processes, and to develop strategies for closing them. The Project's stated mission is to try to provide independent knowledge and analysis that can inform critical decisions affecting the development and commercialization of nanotechnologies.

A source of uncertainty for nanotechnology is regulation. The Project released a 28-page regulatory agenda for the next administration, noting that whichever candidate wins is going to have to deal with this issue, probably sooner rather than later. The next president has the opportunity to ensure that nanotechnology’s benefits will be maximized and its risks identified and mitigated, says the group. 

The report, Nanotechnology Oversight: An Agenda for the Next Administration, calls for the White House and federal agency policymakers to maximize the use of existing laws to improve nanotechnology oversight. Such measures include defining nanomaterials as “new” substances under federal toxics and food laws, thereby enabling the Environmental Protection Agency (EPA) and the Food and Drug Administration (FDA) to consider the novel qualities and effects of nanomaterials. The group addresses whether the Federal Food, Drug and Cosmetic Act, the Toxic Substances Control Act and the Consumer Product Safety Act need to be amended to cover nanotechnology.

The Project notes that more nanotech products are hitting the market. From March, 2006 to February, 2007, the number of manufactured goods using nanotech tripled to 600.  For fiscal 2009, the federal government has devoted $1.5 billion to nanotech, a sum split up between various agencies. Under the Bush administration, EPA has a Nanoscale Materials Stewardship Program, which is endorsed by the Synthetic Organic Chemical Manufacturers Association, the American Chemistry Council and the NanoBusiness Alliance. Some state governments, however, are pushing forward with their own rules on nanotech.

Coincidentally, consumer advocates said this week that food produced by using nanotechnology is quietly coming onto the market, and they want U.S. authorities to force manufacturers to identify them. New consumer products created through nanotechnology are coming on the market at the rate of 3 to 4 per week, according to The Project on Emerging Nanotechnologies.

MassTortDefense has posted on nanotechnology here and here.

 

FDA Advisory Committee Discusses Nano-technology Issues

The FDA’s Advisory Committee for Pharmaceutical Science and Clinical Pharmacology met last week. Among the agenda topics was a discussion of current thinking on issues pertaining to the use of nanotechnology in drug manufacturing, drug delivery, or drug products. (The general function of this committee is to provide advice and recommendations to the agency on regulatory issues.) Scheduled to speak were representatives of the Office of Pharmaceutical Science at CDER, nano-medicine industry leaders, and academics.

MassTortDefense has posted on nano-technology here.

As CDER grapples with questions regarding how to regulate nanomaterial-containing products, several issues have surfaced, including 1) what are the types of nanotechnology applications that will be reviewed by CDER, 2) what are the unique features of these applications that may pose a scientific and/or regulatory challenge to reviewers, 3) are FDA’s current regulatory requirements adequate for the evaluation of nanomaterial-containing products, and 4) what can FDA do to expedite the development of safe and effective nanomaterial-based pharmaceuticals.

Nanotechnology applications in drug development are likely to have a significant impact on the products that FDA regulates. Products containing nanomaterials are being investigated for potential applications as therapeutics, and some products containing nanoscale materials are already on the market. While some of these nanomaterials are nanoscale versions of larger materials used in approved products, other nanomaterials are novel and have never been used in drug products. CDER has initiated a number of activities in order to evaluate how this new technology fits into the current regulatory framework. There have been questions raised about the need for “nano”-specific requirements, in part to aid the development of products containing nanomaterials, and in part because nanomaterial containing products may need to fulfill different regulatory requirements prior to approval.

The FDA established a Nanotechnology Task Force, which issued a report in July 2007. In the task force report, recommendations were made regarding FDA’s future direction for regulating nanomaterial-containing products. Guidance development was included as one the recommendations. FDA believes, however, that the preclinical studies currently required of sponsors are very comprehensive, and include many studies that measure endpoints that could predict possible injury in many organ systems. While general issues have been raised, no one has clearly communicated in what respect the current requirements might be lacking in their capacity to assess safety concerns from such products, and what might be other tests that would improve the predictive value of the current regulatory preclinical requirements.

Nevertheless, because it is widely accepted that there are unique features associated with
nanotherapeutic products, these unique features may lead to future challenges for the development, manufacturing, and possibly safety evaluation and review of these products. Accordingly, the committee was set to discuss:

1. Is CDER guidance needed for the development of nanotechnology-derived drug applications?
2. If guidance is needed from CDER, what areas should this guidance focus on?
3. In light of the many definitions of nanotechnology available, how should CDER define nanotechnology, for the purposes of guidance development?
4. Should particle size information be routinely requested of drug developers, regardless of whether nanomaterials are included in the product? How might this information help in the assessment of safety and efficacy of drugs?

Clearly this is no small issue.

 

Two New Studies on the Potential Risks of Nanotechnology

Two studies have just recently been published describing some potentially important features of a promising form of nanotechnology. Articles in the Journal of Toxicological Sciences and Nature Nanotechnology have reported results of experiments in which some multi-walled carbon nanotubes seem able to induce in mice a response similar to that induced by certain asbestos fibers.

Nanotechnology
Many readers of MassTortDefense know that nanotechnology refers to a new field of technology that seeks to manipulate and control products, really matter, on the atomic and molecular scale, typically 100 nanometers or smaller. To give some sense of scale, one nanometer is one billionth, or 10-9 of a meter. A nanometer compared to a meter is the roughly the same ratio as that of a baseball to the size of the Earth. Or another analogy, a nanometer is the length a man's whiskers grow in the time it takes him to lift his razor to his face to shave.


Two main approaches are used in nanotechnology. In a bottom-up approach, materials and devices are built from molecular components which more or less assemble themselves chemically. In a top-down approach, nano-objects are de-constructed from larger entities. While scientists speculated about nanotechnology in the 1950’s, it is really the modern generation of analytical tools such as the most powerful atomic microscopes which allow the potential deliberate manipulation of nanostructures.


What is so fascinating, and potentially useful, about nanotechnology is that normal sized physical phenomena may be altered as the size of the product decreases. Some features may be enhanced, even dominant at smaller sizes. Moreover, a number of physical, mechanical, electrical, or other properties can change as the size of the particle decreases. As the ratio of surface area to volume changes, the mechanical, thermal and catalytic properties of materials may be altered. Third, novel mechanical properties of nanosystems have also been identified in the lab. For example, opaque substances like copper become transparent; inert materials like platinum become catalysts; some stable substances like aluminum become combustible. Similarly, some solids turn into liquids even at room temperature.


Examples of nanotechnology include new polymers, and computer chips. Nanotechnologies have already found commercial application in suntan lotions, cosmetics, protective coatings, and stain resistant apparel. Significant research is being done on the targeted delivery of drugs to tumors or infections sites using nanotechnology.


Potential Issues
As with any new technology, questions about potential health and environmental risks have been raised. The unique properties of nano-materials make them at once attractive to product makers, but also raise questions about whether conventional thinking about product safety are adequate. For example, the enhanced catalytic activity of certain nano-materials may raise potential questions about their theoretical interaction with biomaterials. Moreover, as seen in the two new studies, the size of the particles raises issues in their own right.


Carbon Nanotubes
In both studies, suspensions of carbon nanotubes were injected into the abdominal cavities of mice, and the results compared against asbestos as a positive control for mesothelioma. Carbon nanotubes are generally made from sheets of graphite no thicker than an atom—about a nanometer, or one billionth of a meter wide—and formed into cylinders, with the diameter varying from a few nanometers up to tens of nanometers. They are excellent conductors of electricity. Carbon nanotubes can also be used to reinforce polymers to create very strong plastics. Carbon nanotubes show promise as building blocks for computer chips that are smaller and faster than those made of silicon. Economists predict that the market for carbon nanotubes will grow to more than $1 billion by 2014.

The Studies
In the JTS study, Atsuya Takagi, et al., “Induction of mesothelioma in p53+/− mouse by intraperitoneal application of multi-wall carbon nanotubes,” J. Toxicol. Sci., Vol. 33: No. 1, 105-116 (2008), researchers tested the hypothesis that due to their fibrous shape and embedded iron content multi-walled carbon nanotubes would have carcinogenic potential similar to asbestos. Blue asbestos (crocidolite), which is known to cause mesothelioma, and fullerene aggregates, which were hypothesized not to cause mesothelioma, were also studied so the results could be compared. Examination of the mice from 10 days to 25 weeks after exposure revealed that the MWCNT and asbestos both resulted in the formation of cancerous lesions that the authors saw as consistent with the disease mesothelioma. (The mice exposed to the other control did not develop these lesions.) The authors suggest that these results point out the possibility that carbon-made fibrous or rod-shaped micrometer particles may share the carcinogenic mechanisms postulated for asbestos. The researchers suggest that the aspect (length/width) ratio and biopersistence of MWCNT may be important factors in understanding their effect on the body.


In the NN study, C. Poland, et al., Carbon nanotubes introduced into the abdominal cavity display asbestos-like pathogenic behavior in a pilot study, Nature Nanotechnology, Published online: 20 May 2008 (doi:10.1038/nnano.2008.111), researchers tested the hypothesis that long straight nanotubes act like long straight asbestos fibers and can cause injury like that seen in mesothelioma. They reported that exposing the mesothelial lining of the body cavity of mice, as a surrogate for the mesothelial lining of the chest cavity, to long multiwalled carbon nanotubes results in asbestos-like, length-dependent, pathogenic behavior. They used various materials for comparison: long, straight MWCNT, short tangled MWCNT, long-fiber amosite asbestos, short-fiber amosite, and a nonfibrous nanoparticulate carbon black material as a control. Tissue samples measured at 7 days were examined for the formation of scar-like lesions called granulomas that often typify the body's response to long fibers. They observed that the mice exposed to the long straight fiber asbestos and the long straight MWCNT showed the presence of inflammatory proteins, cells and granulomas, but not the other substances.

What to Make of the Results
The two studies suggest a need for a careful ongoing assessment of the potential for MWCNT to cause injury. They do not prove or even strongly suggest that nanotubes can cause cancer. The route of exposure is a crucial aspect of toxicology and here it was injection and not inhalation; neither study addresses the question whether inhalation of MWCNT leads to serious health effects like asbestos. It is not clear that carbon nanotubes will become airborne and be inhaled, or whether, if they do reach the lungs, they can get to the mesothelium to cause the effects seen here in mice. Another recent study showed that when mice inhaled nanotubes their lungs returned to normal within one or two months.


Of course, both studies are animal studies, and one used mice that have been specially bred to be susceptible to cancer. Measuring dose is not necessarily easy with nanomaterials, and it is unclear what constitutes an appropriate dose in mice to correlate with human exposures and risk. It is unclear that any humans are or can be exposed to MWCNT in quantities sufficient to induce the effect seen here in mice. If there is a potential hazard, there will be no disease if workers are not overly exposed to long nanotubes. Risk is composed of two parts – hazard and exposure.


Confounding factors involved include the presence of metals, like iron, in the nanotube samples. The JTS study explicitly could not rule out the iron contaminant within the MWCNT samples as the agent responsible for promoting the formation of the cancerous lesions.

Given the importance of this new field, and this new type of product, counsel involved in toxic tort and product liability  litigation will want to keep a close eye on the developing science.