Tag Archives: MWCNT

Multi-walled carbon nanotubes, cancer, and the US National Institute of Occupational Health and Safety’s (NIOSH) latest findings

A Mar. 11, 2013 news item on Nanowerk reveals some of the latest research performed by US National Institute of Occupational Health Safety (NIOSH) researchers into the question of whether or not multi-walled carbon nanotubes (MWCNT) cause cancer,

Earlier today, at the annual meeting of the Society of Toxicology, NIOSH researchers reported preliminary findings from a new laboratory study in which mice were exposed by inhalation to multi-walled carbon nanotubes (MWCNT). The study was designed to investigate whether these tiny particles have potential to initiate or promote cancer. By “initiate,” we mean the ability of a substance to cause mutations in DNA that can lead to tumors. By “promote,” we mean the ability of a substance to cause cells that have already sustained such DNA mutations to then become tumors.

It is very important to have new data that describe the potential health hazards that these materials might represent, so that protective measures can be developed to ensure the safe advancement of nanotechnology in the many industries where it is being applied.

The Mar. 11, 2013 posting (which originated the news item) by Vincent Castranova, PhD; Charles L Geraci, PhD; Paul Schulte, PhD  on the NIOSH blog provides details about the experimental protocols and the outcome of the experiments,

In the NIOSH study, a group of laboratory mice were injected with a chemical that is a known cancer initiator, methylcholanthrene.  Another group of mice were injected with a saline solution as a control group.  The mice then were exposed by inhalation either to air or to a concentration of MWCNT.   These protocols enabled the researchers to investigate whether MWNCT alone would initiate cancer in mice, or whether MWCNT would promote cancer where the initiator, methylcholanthrene, had already been applied.

Mice receiving both the initiator chemical plus exposure to MWCNT were significantly more likely to develop tumors (90% incidence) and have more tumors (an average of 3.3 tumors/mouse lung) than mice receiving the initiator chemical alone (50% of mice developing tumors with an average of 1.4 tumors/lung).  Additionally, mice exposed to MWCNT and to MWCNT plus the initiator chemical had larger tumors than the respective control groups.  The number of tumors per animal exposed to MWCNT alone was not significantly elevated compared with the number per animal in the controls.  These results indicate that MWCNT can increase the risk of cancer in mice exposed to a known carcinogen.  The study does not suggest that MWCNTs alone cause cancer in mice.

That last sentence is quite important because (from the NIOSH blog post),

Several earlier studies in the scientific literature indicated that MWCNT could have the potential to initiate or promote cancer. The new NIOSH study is the first to show that MWCNT is a cancer promoter in a laboratory experiment, and reports the growth of lung tumors in laboratory mice following inhalation exposure to MWCNT rather than injection, instillation, or aspiration.  Inhalation exposure most closely resembles the exposure route of greatest concern in the workplace. In the study, laboratory mice were exposed to one type of MWCNT through inhalation at a concentration of 5 milligrams per cubic meter of air for five hours per day for a period of 15 days.

Risk of occupational cancer depends on the potency of a given substance to cause or promote cancer and the concentration and duration of worker exposure to that substance.  This research is an important step in our understanding of the hazard associated with MWCNT, but before we can determine whether MWCNT pose an occupational cancer risk, we need more information about actual exposure levels and the types and nature of MWCNT being used in the workplace, and how that compares to the material  used in this study.

This study is part of a larger program designed to establish safety practices with regard to handling nanomaterials/nanoparticles (from the NIOSH blog post),

These laboratory studies are part of a strategic program of NIOSH research to better understand the occupational health and safety implications of nanoparticle exposure, and to make authoritative science-based recommendations for controlling exposures so that the technology is developed responsibly as the research advances, and the societal benefits of nanotechnology can be realized.  NIOSH has worked closely with diverse public and private sector partners over the past decade to incorporate occupational health and safety into practical strategies for safe development of this revolutionary technology. More information is available on the NIOSH nanotechnology topic page.

There is no mention in the blog post as to whether the MWCNTs in this latest work were long or short or a mixture of both. Unfortunately, the study has not yet been published in a journal, so it’s not yet available for reading purposes. I did mention carbon nanotubes and toxicity in a Jan. 16, 2013 posting about a recent study,

Researchers at the University College of London (UCL), France’s Centre national de la recherche scientifique (CNRS), and Italy’s University of Trieste have determined that carbon nanotube toxicity issues can be addressed be reducing their length and treating them chemically.

While I find this latest work from NIOSH interesting, it’s hard for me to understand why there’s no mention of length. Unless, the NIOSH work is focused on what happens when MWCNTs are inhaled along with known cancer initiators and they believe that length is not a factor.

ETA Mar. 15, 2013: I did find get some information about the length (long carbon nanotubes for the most part) as per this Mar. 14, 2013 posting or you can find the update in my Mar. 15, 2013 posting here.

Canada-US Regulatory Cooperation Council’s Nanotechnology Work Plan

Thanks for Lynn L. Bergeson for her Dec. 1, 2012 posting on the Nanotechnology Now website for the information about a Nov. 28, 2012 webinar that was held to discuss a Nanotechnology Work Plan developed by the joint Canada-US Regulatory Cooperation Council (or sometimes it’s called the US-Canada Regulatory Cooperation Council),

The RCC requested that industry provide more information on the commercial distribution of nanomaterials, as well as more transparency by claiming confidentiality of only that information absolutely critical to market advantage.

To compare risk assessment and risk management practices to highlight and identify best practices, data gaps, and differences between the two jurisdictions, the RCC sought nominations of a nanomaterial substance for a case study. Four nanomaterial substances were nominated: multiwall carbon nanotubes, nanocrystalline cellulose, nano silver, and titanium dioxide. The RCC has selected multiwall carbon nanotubes for the case study. The RCC intends to hold in March 2013 a workshop in Washington, D.C., to discuss information collected to date and approaches moving forward. In spring 2013, the RCC will hold one or two conference calls or webinars to discuss information gathered between countries and the path forward. Finally, in fall 2013, the RCC expects to hold a stakeholder consultation/workshop on results to date.

Here’s some background on the RCC. First announced in February 2011, the RCC had its first ‘stakeholder’ session (attended by approximately 240)  in January 2012 in Washington, DC. where a series of initiatives, including nanotechnology, were discussed (from the US International Trade Administration RCC Stakeholder Outreach webpage),

Agriculture and Food, Session A

  • Perimeter approach to plant protection

Agriculture and Food, Session B

  • Crop protection products

Agriculture and Food, Session C

  • Meat/poultry – equivalency
  • Meat/poultry – certification requirements
  • Meat cut nomenclature

Agriculture and Food, Session D

  • Veterinary drugs
  • Zoning for foreign animal disease

Agriculture and Food, Session E

  • Financial protection to produce sellers

Agriculture and Food, Session F

  • Food safety – common approach
  • Food safety – testing

Road Transport – Motor Vehicles

  • Existing motor vehicle safety standards
  • New motor vehicle safety standards

Air Transport

  • Unmanned aircraft

Transportation

  • Intelligent Transportation Systems

Transportation

  • Dangerous goods means of transportation

Marine Transport

  • Safety and security framework & arrangement for the St. Lawrence Seaway & Great Lakes System
  • Marine transportation security regulations
  • Recreational boat manufacturing standards
  • Standard for lifejackets

Rail Transport

  • Locomotive Emissions
  • Rail Safety Standards

Environment

  • Emission standards for light-duty vehicles

Personal Care Products & Pharmaceuticals

  • Electronic submission gateway
  • Over-the-counter products – common monographs
  • Good manufacturing practices

Occupational Safety Issues

  • Classification & labelling of workplace hazardous chemicals

Nanotechnology

  • Nanotechnology

Led jointly by senior officials from Canada and the United States, the purpose of the various technical review sessions was to seek expert advice and technical input from the approximately 240 stakeholders in attendance.

Since the Jan. 2012 meeting, a Nanotechnology Work Plan has been developed and that’s what was recently discussed at the Nov. 28, 2012 webinar. I did find more on a Canadian government website, Canada’s Economic Action Plan Nanotechnology Work Plan webpage,

Nanotechnology Work Plan

 Canada Leads: Karen Dodds, Assistant Deputy Minister, Science and Technology Branch, Environment Canada (EC)

Hilary Geller, Assistant Deputy Minister, Healthy Environments and Consumer Safety Branch, Health Canada (HC)

U.S. Lead: Margaret Malanoski, Office of Information and Regulatory Affairs, Office of Management and Budget

Deliverable Outcome: Share information and develop common approaches, to the extent possible, on foundational regulatory elements, including criteria for determining characteristics of concern/no concern, information gathering, approaches to risk assessment and management, etc. Develop joint initiatives to align regulatory approaches in specific areas such that consistency exists for consumers and industry in Canada and the US.

Principles: Identification of common principles for the regulation of nanomaterials to help ensure consistency for industry and consumers in both countries

3-6 months:

Canada provides initial feedback on US “Policy Principles for the US Decision-Making Concerning Regulation and Oversight of Applications of Nanotechnology and Nanomaterials”.

6-12 months:

Countries complete an initial draft of shared principles for the regulation of nanomaterials.

12-18 months:

Update of draft principles informed from on-going stakeholder and expert consultations.

18th month:

Stakeholder consultation / workshop on results to date and future ongoing engagement.

Beyond 18 months:

Countries complete final draft of shared principles for the regulation of nanomaterials.

Workplan for Industrial Nanomaterials

Priority-Setting: Identify common criteria for determining characteristics of industrial nanomaterials of concern/no-concern

1-3 months:

  1. Define and finalize workplan (1st month)
  2. Develop mechanisms for stakeholder outreach and engagement (1st month)
  3. Conference call with relevant stakeholders to share and discuss workplan and call for Industry to volunteer nanomaterials for joint CAN/US review

3-6 months:

Share available scientific evidence regarding characteristics of industrial nanomaterials including that obtained from existing international fora (e.g. OECD Working Party on Manufactured Nanomaterials [Canada is a lead in the OECD Working Party on Manufactured Nanomaterials]).

8th month:

Stakeholder workshop to discuss information collected to date and approaches moving forward.

6-12 months:

Initiate an analysis of characteristics of select nanomaterials: similarities, differences, reasons for them.

Initiate discussions on approaches to consider for common definitions and terminology.

12th month:

Second conference call with relevant stakeholders to discuss non-CBI information gathered between the Countries and to discuss path forward in terms of development of reports and analyses.

12-18 months:

Develop draft criteria for determining characteristics of industrial nanomaterials of concern/no-concern.

15th month:

Third conference call with relevant stakeholders to discuss progress and to prepare for the upcoming stakeholder consultation/workshop.

Here’s information for the leads should you feel compelled to make contact,

Canada

(Lead) Karen Dodds, Assistant Deputy Minister, Science and Technology, Environment Canada ([email protected]; ph. 613- 819-934-6851)

Hilary Geller, Assistant Deputy Minister, Healthy Environments and Consumer Safety Branch ([email protected]; ph. 613-946-6701)

United States

(Lead) Margaret Malanoski, Office of Management and Budget ([email protected])

I gather that the ‘stakeholders’ are business people, researchers, and policy analysts/makers as there doesn’t seem to be any mechanism for public consultation or education, for that matter.

Nanomaterials and toxicology (US Environmental Protection Agency and National Institute of Occupational Health and Safety)

It seems to be ‘toxicology and nanomaterials’ season right now. In addition to the ISO (International Standards Organization) technical report on nanomaterials and toxicology which was released in early June (mentioned in my June 4, 2012 posting), the US Environmental Protection Agency (EPA) and the US National Institute of Occupational Safety and Health (NIOSH) have released new reports.

Yesterday (July 2, 2012), the EPA posted a notice on the US Federal Register about a report, a commenting period, and a public information exchange meeting for “Nanomaterial Case Study: A Comparison of Multiwalled Carbon Nanotubes and Decabromodiphenyl Ether Flame-Retardant Coatings Applied to Upholstery Textiles.”

As I noted in an Aug. 27, 2010 posting, the EPA has adopted a very interesting approach to studying possible toxicological effects due to nanomaterials (and other materials),

Such case studies do not represent completed or even preliminary assessments; rather, they are intended as a starting point in a process to identify and prioritize possible research directions to support future assessments of nanomaterials.

Part of the rationale for focusing on a series of nanomaterial case studies is that such materials and applications can have highly varied and complex properties that make considering them in the abstract or in generalities quite difficult. Different materials and different applications of a given material could raise unique questions or issues as well as some issues that are common to various applications of a given nanomaterial or even to different nanomaterials. After several individual case studies have been examined, refining a strategy for nanomaterials research to support long-term assessment efforts should be possible. (p. 19 PDF, p. 1-1 in print version of a  US EPA silver nanomaterials draft report)

The July 3, 2012 news item on Nanowerk offers more detail about this latest case study (Note: I have removed a link),

EPA announces the release of the draft report, Nanomaterial Case Study: A Comparison of Multiwalled Carbon Nanotube and Decabromodiphenyl Ether Flame-Retardant Coatings Applied to Upholstery Textiles (External Review Draft), for public viewing and comment. This was announced in a July 2, 2012 Federal Register Notice  along with information about the upcoming public Information Exchange Meeting scheduled for October 29, 2012. The purpose of this meeting is to receive comments and questions on the draft document, as well as provide information on the draft document and a workshop process that it will be used in, which is being conducted independently by RTI International, a contractor for EPA. The deadline for comments on the draft document is August 31, 2012. [emphases mine]

The notice on the EPA website offers details and extensive links to satisfy your information needs on this matter,

The draft document is intended to be used as part of a process to identify what is known and, more importantly, what is not yet known that could be of value in assessing the broad implications of specific nanomaterials. Like previous case studies (see History/ Chronology below [on the EPA website]), this draft case study on multiwalled carbon nanotubes (MWCNTs) is based on the comprehensive environmental assessment (CEA) approach, which consists of both a framework and a process. Unlike previous case studies this case study incorporates information about a traditional (i.e., “non-nano-enabled”) product, against which the MWCNT flame-retardant coating applied to upholstery textiles (i.e., the “nano-enabled” product) can be compared. The comparative element serves dual-purposes: 1) to provide a more robust database that facilitates identification of data gaps related to the nano-enabled product and 2) to provide a context for identifying key factors and data gaps for future efforts to evaluate risk-related trade-offs between a nano-enabled and non-nano-enabled product.

This draft case study does not represent a completed or even a preliminary assessment of MWCNTs; rather, it uses the CEA framework to structure information from available literature and other resources (e.g., government reports) on the product life cycle, fate and transport processes in various environmental media, exposure-dose characterization, and impacts in human, ecological, and environmental receptors. Importantly, information on other direct and indirect ramifications of both primary and secondary substances or stressors associated with the nanomaterial is also included when available. The draft case study provides a basis for the next step of the CEA process, whereby collective judgment is used to identify and prioritize research gaps to support future assessment efforts that inform near-term risk management goals.

Meanwhile, NIOSH has released a safety guide (from the June 29, 2012 news item on Nanowerk),

The National Institute for Occupational Safety and Health (NIOSH) has published “General Safe Practices for Working with Engineered Nanomaterials in Research Laboratories” (pdf).

With the publication of this document, NIOSH hopes to raise awareness of the occupational safety and health practices that should be followed during the synthesis, characterization, and experimentation with engineered nanomaterials in a laboratory setting. The document contains recommendations on engineering controls and safe practices for handling engineered nanomaterials in laboratories and some pilot scale operations. This guidance was designed to be used in tandem with well-established practices and the laboratory’s chemical hygiene plan. As our knowledge of nanotechnology increases, so too will our efforts to provide additional guidance materials for working safely with engineered nanomaterials.

Here is more information  from the executive summary of the General Safe Practices for Working with Engineered Nanomaterials in Research Laboratories,

Risk Management

Risk management is an integral part of occupational health and safety. Potential expo­sures to nanomaterials can be controlled in research laboratories through a flexible and adaptive risk management program. An effective program provides the framework to anticipate the emergence of this technology into laboratory settings, recognize the po­tential hazards, evaluate the exposure to the nanomaterial, develop controls to prevent or minimize exposure, and confirm the effectiveness of those controls.

Hazard Identification

Experimental animal studies indicate that potentially adverse health effects may result from exposure to nanomaterials. Experimental studies in rodents and cell cultures have shown that the toxicity of ultrafine particles or nanoparticles is greater than the toxicity of the same mass of larger particles of similar chemical composition.

Research demonstrates that inhalation is a significant route of exposure for nanoma­terials. Evidence from animal studies indicates that inhaled nanoparticles may deposit deep in lung tissue, possibly interfering with lung function. It is also theorized that nanoparticles may enter the bloodstream through the lungs and transfer to other or­gans. Dermal exposure and subsequent penetration of nanomaterials may cause local or systemic effects. Ingestion is a third potential route of exposure. Little is known about the possible adverse effects of ingestion of nanomaterials, although some evidence sug­gests that nanosized particles can be transferred across the intestinal wall.

Exposure Assessment

Exposure assessment is a key element of an effective risk management program. The ex­posure assessment should identify tasks that contribute to nanomaterial exposure and the workers conducting those tasks. An inventory of tasks should be developed that in­cludes information on the duration and frequency of tasks that may result in exposure, along with the quantity of the material being handled, dustiness of the nanomaterial, and its physical form. A thorough understanding of the exposure potential will guide exposure assessment measurements, which will help determine the type of controls re­quired for exposure mitigation.

Exposure Control

Exposure control is the use of a set of tools or strategies for decreasing or eliminating worker exposure to a particular agent. Exposure control consists of a standardized hi­erarchy to include (in priority order): elimination, substitution, isolation, engineering controls, administrative controls, or if no other option is available, personal protective equipment (PPE).

Substitution or elimination is not often feasible for workers performing research with nanomaterials; however, it may be possible to change some aspects of the physical form of the nanomaterial or the process in a way that reduces nanomaterial release.

Isolation includes the physical separation and containment of a process or piece of equipment, either by placing it in an area separate from the worker or by putting it within an enclosure that contains any nanomaterials that might be released.

Engineering controls include any physical change to the process that reduces emissions or exposure to the material being contained or controlled. Ventilation is a form of engi­neering control that can be used to reduce occupational exposures to airborne particu­lates. General exhaust ventilation (GEV), also known as dilution ventilation, permits the release of the contaminant into the workplace air and then dilutes the concentration to an acceptable level. GEV alone is not an appropriate control for engineered nano­materials or any other uncharacterized new chemical entity. Local exhaust ventilation (LEV), such as the standard laboratory chemical hood (formerly known as a laboratory fume hood), captures emissions at the source and thereby removes contaminants from the immediate occupational environment. Using selected forms of LEV properly is ap­propriate for control of engineered nanomaterials.

Administrative controls can limit workers’ exposures through techniques such as us­ing job-rotation schedules that reduce the time an individual is exposed to a substance. Administrative controls may consist of standard operating procedures, general or spe­cialized housekeeping procedures, spill prevention and control, and proper labeling and storage of nanomaterials. Employee training on the appropriate use and handling of nanomaterials is also an important administrative function.

PPE creates a barrier between the worker and nanomaterials in order to reduce expo­sures. PPE may include laboratory coats, impervious clothing, closed-toe shoes, long pants, safety glasses, face shields, impervious gloves, and respirators.

Other Considerations

Control verification or confirmation is essential to ensure that the implemented tools or strategies are performing as specified. Control verification can be performed with traditional industrial hygiene sampling methods, including area sampling, personal sampling, and real-time measurements. Control verification may also be achieved by monitoring the performance parameters of the control device to ensure that design and performance criteria are met.

Other important considerations for effective risk management of nanomaterial expo­sure include fire and explosion control. Some studies indicate that nanomaterials may be more prone to explosion and combustion than an equivalent mass concentration of larger particles.

Occupational health surveillance is used to identify possible injuries and illnesses and is recommended as a key element in an effective risk management program. Basic medical screening is prudent and should be conducted under the oversight of a qualified health-care professional. (pp. 9 – 11 PDF or pp. vii – ix in print)

The guidance as per the executive summary seems to rely heavily on what I imagine are industrial hygiene practices that should be followed whether or not laboratories are researching nanomaterials.

Carbon nanotubes, neurons, and spinal cords (plus a brief plug for the Isabelle Stengers talk being livestreamed today)

Mention scaffolds, nanotechnology, and cells and I think of tissue engineering. Michael Berger’s March 2, 2012 Spotlight essay, Exploring the complexity of nanomaterial-neural interfaces, on Nanowerk mentions all three. From the essay,

Carbon nanotubes, like the nervous cells of our brain, are excellent electrical signal conductors and can form intimate mechanical contacts with cellular membranes, thereby establishing a functional link to neuronal structures. …

Now, researchers have, for the first time, explored the impact of carbon nanotube scaffolds on multilayered neuronal networks. Up to now, all known effects of carbon nanotubes on neurons – namely their reported ability to potentiate neuronal signaling and synapses – have been described in bi-dimensional cultured networks where nanotube/neuron hybrids were developed on a monolayer of dissociated brain cells.

In their work, a team of scientists in Italy, led by professors Maurizio Prato and Laura Ballerini, used slices from the spinal cords of mice to model multilayer-tissue complexity. They interfaced these spinal segments to multi-walled carbon nanotube (MWCNT) scaffolds for weeks at a time to see whether and how the interactions at the monolayer level are translated to multilayered nerve tissues.

I found this part of the explanation a little easier to understand,

According to the team, interfacing spinal cord explants [cells removed from living tissue and cultivated in artificial media] to purified carbon nanotubes over a longer period (weeks) induces two major effects: First, the number and length of neuronal fibers outgrowing the spinal segment increases, associated with changes in growth cone activity and in fiber elastomechanical properties. And, secondly, the researchers point out that after weeks of MWCNT  interfacing, neurons located at as far as five cell layers from the substrate display an increased efficacy in synaptic responses – which could represent either an improvement or a pathological behavior – presumably mediated by ongoing plasticity driven by the neuron/MWCNT hybrids.

If this increased efficacy in synaptic responses should represent an improvement, it suggests to me that it could be helpful with spinal cord injuries at some point. The researchers themselves are not speculating that far into the future (from the Berger essay),

They [Prato and Ballerini] note that this is important because it exploits the design of artificial micro- and nanoscale devices that cooperate with neuronal network activity, thereby creating hybrid structures able to cross the barriers between artificial devices and neurons.

Taken in conjunction with today’s (March 5, 2012) earlier posting (Carbon and neural implants), it seems that there is a great deal of work being done to integrate ‘machine’ and flesh so we achieve machine/flesh. While I don’t believe that philosopher and chemist Isabelle Stengers will be addressing those specific issues in her  talk, Cosmopolitics, being livestreamed here later today (3:30 pm PST) from Halifax (Nova Scotia), she does touch on this,

Professor Stengers’ keynote address will examine sciences and the consequences of what has been called progress. Is it possible to reclaim modern practices, to have them actively taking into account what they felt entitled to ignore in the name of progress? Or else, can they learn to “think with” instead of define and judge?  [emphasis mine]

I don’t know what she means by ‘think with’ but it strikes me that it represents a significant shift of thought as it implies a relationship that is not separated (or bounded) in the ways we have traditionally observed. Defining and judging are made possible by the notion of separation (boundaries); machine and flesh have been viewed from the perspective of boundaries and separation; machine/flesh seems more like ‘thinking with’.