Category Archives: health and safety

Identifying minute amounts of nanomaterial in environmental samples

It’s been a while since I’ve had a story from one of Germany’s Franhaufer Institutes. Their stories are usually focused on research that’s about to commercialized but that’s not the case this time according to an April 28, 2016 news item on Nanowerk,

It is still unclear what the impact is on humans, animals and plants of synthetic nanomaterials released into the environment or used in products. It’s very difficult to detect these nanomaterials in the environment since the concentrations are so low and the particles so small. Now the partners in the NanoUmwelt project have developed a method that is capable of identifying even minute amounts of nanomaterials in environmental samples.

An April 28, 2016 Fraunhofer Institute press release, which originated the news item, provides more detail about the technology and about the NanoUmwelt project along with a touch of whimsy,

Tiny dwarves keep our mattresses clean, repair damage to our teeth, stop eggs sticking to our pans, and extend the shelf life of our food. We are talking about nanomaterials – “nano” comes from the Greek word for “dwarf”. These particles are just a few billionths of a meter small, and they are used in a wide range of consumer products. However, up to now the impact of these materials on the environment has been largely unknown, and information is lacking on the concentrations and forms in which they are present there. “It’s true that many laboratory studies have examined the effect of nanomaterials on human and animal cells. To date, though, it hasn’t been possible to detect very small amounts in environmental samples,” says Dr. Yvonne Kohl from the Fraunhofer Institute for Biomedical Engineering IBMT in Sulzbach.

A millionth of a milligram per liter 

That is precisely the objective of the NanoUmwelt project. The interdisciplinary project team is made up of eco- and human toxicologists, physicists, chemists and biologists, and they have just managed to take their first major step forward in achieving their goal: they have developed a method for testing a variety of environmental samples such as river water, animal tissue, or human urine and blood that can detect nanomaterials at a concentration level of nanogram per liter (ppb – parts per billion). That is equivalent to half a sugar cube in the volume of water contained in 1,000 competition swimming pools. Using the new method, it is now possible to detect not just large amounts of nanomaterials in clear fluids, as was previously the case, but also very few particles in complex substance mixtures such as human blood or soil samples. The approach is based on field-flow fractionation (FFF), which can be used to separate complex heterogeneous mixtures of fluids and particles into their component parts – while simultaneously sorting the key components by size. This is achieved by the combination of a controlled flow of fluid and a physical separation field, which acts perpendicularly on the flowing suspension.

For the detection process to work, environmental samples have to be appropriately processed. The team from Fraunhofer IBMT’s Bioprocessing & Bioanalytics Department prepared river water, human urine, and fish tissue to be fit for the FFF device. “We prepare the samples with special enzymes. In this process, we have to make sure that the nanomaterials are not destroyed or changed. This allows us to detect the real amounts and forms of the nanomaterials in the environment,” explains Kohl. The scientists have special expertise when it comes to providing, processing and storing human tissue samples. Fraunhofer IBMT has been running the “German Environmental Specimen Bank (ESB) – Human Samples”since January 2012 on behalf of Germany’s Environment Agency (UBA). Each year the research institute collects blood and urine samples from 120 volunteers in four cities in Germany. Individual samples are a valuable tool for mapping the trends over time of human exposure to pollutants. ”In addition, blood and urine samples have been donated for the NanoUmwelt project and put into cryostorage at Fraunhofer IBMT. We used these samples to develop our new detection method,” says Dr. Dominik Lermen, manager of the working group on Biomonitoring & Cryobanks at Fraunhofer IBMT. After approval by the UBA, some of the human samples in the ESB archive may also be examined using the new method.

Developing new cell culture models

Nanomaterials end up in the environment via different pathways, inter alia the sewage system. Human beings and animals presumably absorb them through biological barriers such as the lung or intestine. The project team is simulating these processes in petri dishes in order to understand how nanomaterials are transported across these barriers. “It’s a very complex process involving an extremely wide range of cells and layers of tissue,” explains Kohl. The researchers replicate the processes in a way as realistic as possible. They do this by, for instance, measuring the electrical flows within the barriers to determine the functionality of these barriers – or by simulating lung-air interaction using clouds of artificial fog. In the first phase of the NanoUmwelt project, the IBMT team succeeded in developing several cell culture models for the transport of nanomaterials across biological barriers. IBMT worked together with the Fraunhofer Institute for Molecular Biology and Applied Ecology IME, which used pluripotent stem cells to develop a model for investigating cardiotoxicity. Empa, the Swiss partner in the project, delivered a placental barrier model for studying the transport of nanomaterials between mother and child.

Next, the partners want to use their method to measure the concentrations of nanoparticles in a wide variety of environmental samples. They will then analyze the results obtained so as to be in a better position to assess the behavior of nanomaterials in the environment and their potential danger for humans, animals, and the environment. “Our next goal is to detect particles in even smaller quantities,” says Kohl. To achieve this, the scientists are planning to use special filters to remove distracting elements from the environmental samples, and they are looking forward to develop new processing techniques.
NanoUmwelt – the objective

The NanoUmwelt research project was launched in October 2014 and will last for 36 months. Its objective is to develop methods for detecting minute amounts of nanomaterials in environmental samples. Using this information, the project partners will assess the effect of nanomaterials on humans, animals, and the environment. They are focusing on commercially significant, slowly degradable, metallic (silver, titanium dioxide), carbonic (carbon nanotubes) and polymer-based (polystyrene) nanomaterials.

http://www.nanopartikel.info/projekte/laufende-projekte/nanoumwelt

NanoUmwelt – the partners

The German Federal Ministry for Education and Research (BMBF) is providing the NanoUmwelt project with 1.8 million euros of funding as part of its NanoCare program. Led by Postnova Analytics GmbH, ten further partners are collaborating together on the project. Besides the Fraunhofer Institutes for Biomedical Engineering IBMT and for Molecular Biology and Applied Ecology IME, these partners include Germany’s Environment Agency, Empa (the Swiss Federal Laboratories for Materials Science and Technology), PlasmaChem GmbH, Senova GmbH (biological sciences and engineering), fzmb GmbH (Research Centre of Medical Technology and Biotechnology), the universities of Trier and Frankfurt, and the Rhine Water Control Station in Worms.

http://www.nanopartikel.info/projekte/laufende-projekte/nanoumwelt

How small is nano?

A nanometer (nm) is a billionth of a meter. To put this into context: the size of a single nanoparticle relative to a football is the same as that of a football relative to the earth. In the main, nanoscopic particles are not new materials. It’s simply that the increased overall surface area of these tiny particles gives them new functionalities as against larger particles of the same material.


The German Environmental Specimen Bank  

The German Environmental Specimen Bank (ESB) provides the country’s Federal Ministry for the Environment, Nature Conservation, Building and Nuclear Safety (BMUB) with a scientific basis both for adopting appropriate measures concerning environment and nature conservation and for monitoring the success of those measures. The human samples collected by the Fraunhofer Institute for Biomedical Engineering IBMT on behalf of Germany’s Environment Agency (UBA) give an overview of human exposure to environmental pollutants.

https://www.umweltprobenbank.de/de

Assuming I’ve understood this correctly, the NanoUmwelt project will be ending in 2017 (36 months in total) and the researchers have expended 1/2 of the time (18 months) allotted to developing a technique for measuring nanomaterials of heretofore unheard of quantities in environmental samples. With that done, researchers are now going to use the technique with human samples over the next 18 months.

Harmonized nano terminology for environmental health and safety

According to Lynn Bergeson’s April 11, 2016 posting on Nanotechnology Now, the European Commission’s Joint Research Centre (JRC) has published a document about harmonizing terminology for environmental health and safety of nanomaterials,

The European Commission (EC) Joint Research Center (JRC) recently published a report entitled NANoREG harmonised terminology for environmental health and safety assessment of nanomaterials, developed within the NANoREG project: “A common European approach to the regulatory testing of nanomaterials.”

The NANoREG harmonised terminology for environmental health and safety assessment of nanomaterials (PDF)  has an unexpected description for itself on p. 8 (Note: A link has been removed),

Consistent  use  of  terminology  is  important  in  any  field  of  science  and  technology  to ensure  common  understanding  of  concepts  and  tools among  experts  and  different stakeholders, such as regulatory authorities, industry and consumers. Several  terms  in  the  field of  environmental  health  and  safety  (EHS)  assessment of nanomaterials  (hereinafter  NMs) have  been  indeed  defined  or  used  by  the  scientific community and various organisations, including   international   bodies,   European authorities, and industry associations.

This  is true  for multidisciplinary  projects  such  as  NANoREG, which  aims  at supporting regulatory  authorities, and  industry,  in  dealing  with EHS issues  of  manufactured NMs (‘nanoEHS’) (http://cordis.europa.eu/project/rcn/107159_en.html,www.nanoreg.eu). Terminology  thus  plays  an  important  role  in  NANoREG’s internal  process  of producing diverse types of output with regulatory relevance (e.g. physicochemical characterisation and test protocols, grouping and read-across approaches, exposure models, a framework for  safety  assessment  of NMs,  etc.). The  process  takes  place  in a  collaborative  effort across severalNANoREG work packages or tasks,  involvingquite a  few partners. Moreover,  the  different  types  of NANoREG output (‘deliverables’) are  addressed  to  a large  audience  of  scientists,  industry  and  regulatory  bodies,  extending beyond  Europe. Hence, a coordinated initiative has been undertaken by the Joint Research Centre (JRC) to harmonise the use of specific wording within NANoREG.

The objective of this JRC report is to disseminate the harmonised terminology that has been developed and used with in NANoREG. This collection of key terms has been agreed upon by all  project  partners and adopted  in  their  activities  and  related  documents, as recommended by the NANoREG internal Guidance Document.

Accordingly,  Section  2  of  the  report  illustrates  the  methodology  used  i)  to  select  key terms  that  form  the  ‘NANoREG  Terminology’,  ii)  to  develop  harmonised  ‘NANoREG Definitions’, and iii) it also explains the thinking that led to the choices made in drafting a  definition.  In  Section  3,  those  definitions, adopted  by  the  project  Consortium,  are reported  in  a  table  format  and  constitute  the  ‘NANoREG  Harmonised  Terminology’. Section 4 summarises the existing literature definitions that have been used as starting point to elaborate, for each key term, a NANoREG Definition. It also shortly discusses the reason(s) behind the choices that have been made in drafting a definition.

2. Methodology

The NANoREG Harmonised Terminology illustrated in this report is not a ‘dictionary’ [emphasis mine] that collects a long list of well-known, well-defined scientific and/or regulatory terms relevant to  the  field  of nanoEHS.  Rather,  the  NANoREG Harmonised  Terminology  focuses  on  a relatively short list of key terms that may be interpreted in various ways, depending on where the reader is located on the globe or on the reader’s scientific area of expertise. Moreover,  it  focuses  on  few  terms  that  are  specifically relevant  in  a  REACH [Registration, Evaluation, Authorization, & Restriction of Chemicals]  context, which represents the regulatory framework of reference for NANoREG.

This is having it both ways. As I read it, what they’re saying is this: ‘Our document is not a dictionary but here are the definitions we’re using and you can use them that way if you like’.

You can find a link to the ‘harmonisation’ document and one other related document on this page.

The Canadian nano scene as seen by the OECD (Organization for Economic Cooperation and Development)

I’ve grumbled more than once or twice about the seemingly secret society that is Canada’s nanotechnology effort (especially health, safety, and environment issues) and the fact that I get most my information from Organization for Economic Cooperation and Development (OECD) documents. That said, thank you to Lynne Bergeson’s April 8, 2016 post on Nanotechnology Now for directions to the latest OECD nano document,

The Organization for Economic Cooperation and Development recently posted a March 29, 2016, report entitled Developments in Delegations on the Safety of Manufactured Nanomaterials — Tour de Table. … The report compiles information, provided by Working Party on Manufactured Nanomaterials (WPMN) participating delegations, before and after the November 2015 WPMN meeting, on current developments on the safety of manufactured nanomaterials.

It’s an international roundup that includes: Australia, Austria, Belgium, Canada, Germany, Japan, Korea, the Netherlands, Switzerland, Turkey, United Kingdom, U.S., and the European Commission (EC), as well as the Business and Industry Advisory Committee to the OECD (BIAC) and International Council on Animal Protection in OECD Programs (ICAPO).

As usual, I’m focusing on Canada. From the DEVELOPMENTS IN DELEGATIONS ON THE SAFETY OF MANUFACTURED NANOMATERIALS – TOUR DE TABLE Series on the Safety of Manufactured Nanomaterials No. 67,

CANADA
National  developments  on  human  health  and  environmental  safety  including  recommendations, definitions, or discussions related to adapting or applying existing regulatory systems or the drafting of new laws/ regulations/amendments/guidance materials A consultation document on a Proposed Approach to Address Nanoscale Forms of Substances on the Domestic  Substances  List was  published  with  a  public  comment  period  ending on  May  17,  2015. The proposed approach outlines the Government’s plan to address nanomaterials considered in commerce in Canada (on  Canada’s  public inventory).  The  proposal is a stepwise  approach to  acquire  and  evaluate information,  followed  by  any  necessary  action. A  follow-up  stakeholder  workshop  is  being  planned  to discuss  next  steps  and  possible  approaches  to prioritize  future  activities. The  consultation document  is available at: http://www.ec.gc.ca/lcpe-cepa/default.asp?lang=En&n=1D804F45-1

A mandatory information gathering survey was published on July 25, 2015. The purpose of the survey is to collect information to determine the commercialstatus of certain nanomaterials in Canada. The survey targets  206  substances  considered  to  be  potentially  in commerce  at  the  nanoscale. The  list  of  206 substances was developed using outcomes from the Canada-United States Regulatory Cooperation Council (RCC)  Nanotechnology  Initiative  to  identify nanomaterial  types. These  nanomaterial  types  were  cross-referenced  with  the Domestic  Substances  List to  develop  a  preliminary  list  of  substances  which are potentially intentionally manufactured at the nanoscale. The focus of the survey aligns with the Proposed Approach to  Address  Nanoscale  Forms  of  Substances  on  the Domestic  Substances  List (see  above)  and certain  types  of  nanomaterials  were  excluded  during the  development  of  the  list  of  substances. The information  being  requested  by  the  survey  includes substance  identification,  volumes,  and  uses.  This information will feed into the Government’s proposed approach to address nanomaterials on the Domestic Substances List. Available at: http://gazette.gc.ca/rp-pr/p1/2015/2015-07-25/html/notice-avis-eng.php

Information on:

a.risk  assessment  decisions, including  the  type  of:  (a)  nanomaterials  assessed; (b) testing recommended; and (c) outcomes of the assessment;

Four substances were notified to the program since the WPMN14 – three surface modified substances and  one  inorganic  substance.  No  actions,  including  additional  data requests,  were  taken  due  to  low expected  exposures  in  accordance  with  the New  Substances  Notifications  Regulations  (Chemicals and Polymers) (NSNR) for two of the substances.  Two of the substances notified were subject to a Significant New Activity Notice. A Significant New Activity notice is an information gathering tool used to require submission  of  additional  information  if  it  is suspected  that  a  significant  new  activity  may  result in  the substance becoming toxic under the Canadian Environmental Protection Act, 1999.

b.Proposals, or modifications to previous regulatory decisions

As  part  of  the  Government’s  Chemicals  Management Plan,  a  review  is  being  undertaken  for  all substances  which  have  been  controlled through  Significant  New  Activity  (SNAc)  notices (see  above).  As part  of  this  activity,  the  Government  is  reviewing past  nanomaterials  SNAc  notices  to  see  if  new information  is  available  to  refine  the  scope  and information  requirements.    As  a  result  of  this  review, 9 SNAc  notices  previously  in  place  for  nanomaterials have  been  rescinded.    This  work  is  ongoing,  and  a complete review of all nanomaterial SNAcs is currently planned to be completed in 2016.

Information related to good practice documents

The Canada-led,  ISO  standards project, ISO/DTR  19716 Nanotechnologies — Characterization  of cellulose  nanocrystals, [emphasis mine] initiated  in  April 2014, is  now at Committee  Draft  (CD)  3-month  ISO ballot, closing    Aug 31, 2015. Ballot comments will be addressed during JWG2 Measurement and Characterization working  group meetings  at  the 18th Plenary  of  ISO/TC229, Nanotechnologies,  being held in Edmonton, Alberta, Sep. 28 – Oct. 2, 2015.

Research   programmes   or   strategies   designed   to  address   human   health   and/   or environmental safety aspects of nanomaterials

Scientific research

Environment Canada continues to support various academic and departmental research projects. This research has to date included studying fate and effects of nanomaterials in the aquatic, sediment, soil, and air  compartments. Funding  in  fiscal  2015-16  continues  to  support  such  projects,  including  sub-surface transportation, determining key physical-chemical parameters to predict ecotoxicity, and impacts of nano-silver [silver nanoparticles]  addition  to  a  whole  lake  ecosystem [Experimental Lakes Area?]. Environment  Canada  has  also  partnered  with  the National Research  Council  of  Canada  recently  to  initiate  a project  on  the  development  of  test  methods  to identify surfaces of nanomaterials for the purposes of regulatory identification and to support risk assessments. In addition,  Environment  Canada  is  working  with  academic laboratories in  Canada  and  Germany  to  prepare guidance to support testing of nanoparticles using the OECD Test Guideline for soil column leaching.

Health  Canada  continues  its  research  efforts  to  investigate  the  effects  of  surface-modified  silica nanoparticles. The   aims   of   these   projects   are  to:   (1) study the importance of size and surface functionalization;  and  (2)  provide a genotoxic profile and  to  identify  mechanistic  relationships  of  particle properties  to  elicited  toxic  responses.  A manuscript reporting  the in  vitro genotoxic,  cytotoxic and transcriptomic  responses  following  exposure  to  silica  nanoparticles  has  recently  been  submitted to  a  peer reviewed journal and is currently undergoing review. Additional manuscripts reporting the toxicity results obtained to date are in preparation.

Information on public/stakeholder consultations;

A consultation document on a Proposed Approach to Address Nanoscale Forms of Substances on the Domestic  Substances  List was  published  with a  public  comment  period ending  on May  17,  2015  (see Question  1).  Comments  were  received  from approximately  20  stakeholders  representing  industry and industry  associations,  as  well  as  non-governmental  organizations. These  comments  will  inform  decision making to address nanomaterials in commerce in Canada.

Information on research or strategies on life cycle aspects of nanomaterials

Canada, along with Government agencies in the United States, Non-Governmental Organizations and Industry,  is  engaged  in  a  project  to  look  at releases  of  nanomaterials  from  industrial  consumer  matrices (e.g., coatings). The objectives of the NanoRelease Consumer Products project are to develop protocols or
methods (validated  through  interlaboratory  testing) to  measure  releases  of  nanomaterials  from  solid matrices as a result of expected uses along the material life cycle for consumer products that contain the nanomaterials. The  project  is  currently  in  the  advanced  stages  of Phase  3  (Interlaboratory  Studies).  The objectives of Phase 3 of the project are to develop robust methods for producing and collecting samples of CNT-epoxy  and  CNT-rubber  materials  under  abrasion  and  weathering scenarios,  and  to  detect  and quantify, to the extent possible, CNT release fractions. Selected laboratories in the US, Canada, Korea and the European Community are finalising the generation and analysis of sanding and weathering samples and the    results    are    being    collected    in    a   data    hub    for    further    interpretation    and    analysis.

Additional details about the project can be found at the project website: http://www.ilsi.org/ResearchFoundation/RSIA/Pages/NanoRelease1.aspx

Under the OECD Working Party on Resource Productivity and Waste (WPRPW), the expert group on waste containing nanomaterials has developed four reflection papers on the fate of nanomaterials in waste treatment  operations.  Canada  prepared the  paper  on  the  fate  of  nanomaterials in  landfills;  Switzerland on the  recycling  of  waste  containing  nanomaterials;  Germany  on  the  incineration  of  waste  containing nanomaterials;  and  France  on  nanomaterials  in wastewater  treatment.  The  purpose  of  these  papers is to provide  an  overview  of  the  existing  knowledge  on the  behaviour  of  nanomaterials  during  disposal operations and identify the information gaps. At the fourth meeting of the WPRPW that took place on 12-14 November 2013, three of the four reflection papers were considered by members. Canada’s paper was presented and discussed at the fifth meeting of the WPRPRW that took place on 8-10 December 2014. The four  papers  were  declassified  by  EPOC  in  June  2015, and  an  introductory  chapter  was  prepared  to  draw these  papers  together. The introductory  chapter  and accompanying  papers  will  be  published in  Fall  2015. At  the sixth  meeting  of  the  WPRPW  in  June – July  2015,  the  Secretariat  presented  a  proposal  for an information-sharing  platform  that  would  allow  delegates  to  share research  and  documents  related  to nanomaterials. During a trial phase, delegates will be asked to use the platform and provide feedback on its use at the next meeting of the WPRPW in December 2015. This information-sharing platform will also be accessible to delegates of the WPMN.

Information related to exposure measurement and exposure mitigation.

Canada and the Netherlands are co-leading a project on metal impurities in carbon nanotubes. A final version  of  the  report  is  expected  to  be ready for WPMN16. All  research has  been completed (e.g. all components are published or in press and there was a presentation by Pat Rasmussen to SG-08 at the Face-to-Face Meeting in Seoul June 2015). The first draft will be submitted to the SG-08 secretariat in autumn 2015. Revisions  will  be  based  on  early  feedback  from  SG-08  participants.  The  next  steps  depend  on  this feedback and amount of revision required.

Information on past, current or future activities on nanotechnologies that are being done in co-operation with non-OECD countries.

A webinar between ECHA [European Chemicals Agency], the US EPA [Environmental Protection Agency] and Canada was hosted by Canada on April 16, 2015. These are  regularly  scheduled  trilateral  discussions  to keep  each  other  informed  of  activities  in  respective jurisdictions.

In  March 2015, Health  Canada  hosted  3  nanotechnology knowledge  transfer sessions  targeting Canadian  government  research  and  regulatory  communities  working  in  nanotechnology.  These  sessions were  an  opportunity  to  share  information  and perspectives  on  the  current  state  of  science supporting  the regulatory  oversight  of  nanomaterials with  Government.  Presenters  provided  detailed  outputs  from  the OECD WPMN including: updates on OECD test methods and guidance documents; overviews of physical-chemical properties, as well as their relevance to toxicological testing and risk assessment; ecotoxicity and fate   test   methods;   human   health   risk   assessment   and   alternative   testing   strategies;   and exposure measurement  and  mitigation.  Guest  speakers  included  Dr  Richard  C.  Pleus  Managing  Director  and  Director of Intertox, Inc and Dr. Vladimir Murashov Special Assistant on Nanotechnology to the Director of National Institute for Occupational Safety and Health (NIOSH).

On   March   4-5, 2015, Industry   Canada   and   NanoCanada co-sponsored  “Commercializing Nanotechnology  in  Canada”,  a  national  workshop  that brought  together  representatives  from  industry, academia and government to better align Canada’s efforts in nanotechnology.  This workshop was the first of  its  kind  in  Canada. It  also  marked  the  official  launch  of  NanoCanada (http://nanocanada.com/),  a national  initiative  that  is  bringing  together stakeholders  from  across  Canada  to  bridge  the  innovation  gap and stimulates emerging technology solutions.

It’s nice to get an update about what’s going on. Despite the fact this report was published in 2016 the future tense is used in many of the verbs depicting actions long since accomplished. Maybe this was a cut-and-paste job?

Moving on, I note the mention of the Canada-led,  ISO  standards project, ISO/DTR  19716 Nanotechnologies — Characterization  of cellulose  nanocrystals (CNC). For those not familiar with CNC, the Canadian government has invested hugely in this material derived mainly from trees, in Canada. Other countries and jurisdictions have researched nanocellulose derived from carrots, bananas, pineapples, etc.

Finally, it was interesting to find out about the existence of  NanoCanada. In looking up the Contact Us page, I noticed Marie D’Iorio’s name. D’Iorio, as far as I’m aware, is still the Executive Director for Canada’s National Institute of Nanotechnology (NINT) or here (one of the National Research Council of Canada’s institutes). I have tried many times to interview someone from the NINT (Nils Petersen, the first NINT ED and Martha Piper, a member of the advisory board) and more recently D’Iorio herself only to be be met with a resounding silence. However, there’s a new government in place, so I will try again to find out more about the NINT, and, this time, NanoCanada.

Inhaling buckyballs (C60 fullerenes)

Carbon nanotubes (also known as buckytubes) have attracted most of the attention where carbon nanomaterials and health and safety are concerned. But, University of Michigan researchers opted for a change of pace and focused their health and safety research on buckyballs (also known as C60 or fullerenes) according to a Feb. 24, 2016 news item on Nanowerk,

Scientists at the University of Michigan have found evidence that some carbon nanomaterials can enter into immune cell membranes, seemingly going undetected by the cell’s built-in mechanisms for engulfing and disposing of foreign material, and then escape through some unidentified pathway. [emphasis mine]

The researchers from the School of Public Health and College of Engineering say their findings of a more passive entry of the materials into cells is the first research to show that the normal process of endocytosis-phagocytosis isn’t always activated when cells are confronted with tiny Carbon 60 (C60 ) molecules.

A Feb. 23, 2016 University of Michigan news release (also on EurekAlert but dated Feb. 24, 2016), which originated the news item, provides more detail about the research,

… This study examined nanomaterials known as carbon fullerenes, in this case C60, which has a distinct spherical shape.

Over the last decade, scientists have found these carbon-based materials useful in a number of commercial products, including drugs, medical devices, cosmetics, lubricants, antimicrobial agents and more. Fullerenes also are produced in nature through events like volcanic eruptions and wildfires.

The concern is that however exposed, commercially or naturally, little is known about how inhaling these materials impacts health.

“It’s entirely possible that even tiny amounts of some nanomaterials could cause altered cellular signaling,” said Martin Philbert, dean and professor of toxicology at the U-M School of Public Health.

Philbert said much of the previously published research bombarded cells with large amounts of particle clusters, unlike a normal environmental exposure.

The U-M researchers examined various mechanisms of cell entry through a combination of classical biological, biophysical and newer computational techniques, using models developed by a team led by Angela Violi to determine how C60 molecules find their way into living immune cells of mice.

They found that the C60 particles in low concentrations were entering the membrane individually, without perturbing the structure of the cell enough to trigger its normal response.

“Computational modeling of C60 interacting with lipid bilayers, representative of the cellular membrane, show that particles readily diffuse into biological membranes and find a thermodynamically stable equilibrium in an eccentric position within the bilayer,” said Violi, U-M professor of mechanical engineering, chemical engineering, biomedical engineering, and macromolecular science and engineering.

“The surprising contribution of passive modes of cellular entry provides new avenues for toxicological research, as we still don’t know exactly what are the mechanisms that cause this crossing.”

So, while the buckyballs enter cells, they also escape from them somehow. I wonder if the mechanisms that allow them to enter the cells are similar to the ones that allow them to escape. Regardless, here’s a link to and a citation for the paper,

C60 fullerene localization and membrane interactions in RAW 264.7 immortalized mouse macrophages by K. A. Russ, P. Elvati, T. L. Parsonage, A. Dews, J. A. Jarvis, M. Ray, B. Schneider, P. J. S. Smith, P. T. F. Williamson, A. Violi and M. A. Philbert. Nanoscale, 2016, 8, 4134-4144 DOI: 10.1039/C5NR07003A First published online 25 Jan 2016

This paper is behind a paywall.

Hypersensitivity to nanomedicine: the CARPA reaction

There is some intriguing research (although I do have a reservation) into some unexpected side effects that nanomedicine may have according to a Feb. 23, 2016 news item on phys.org,

Keywords such as nano-, personalized-, or targeted medicine sound like bright future. What most people do not know, is that nanomedicines can cause severe undesired effects for actually being too big! Those modern medicines easily achieve the size of viruses which the body potentially recognizes as foreign starting to defend itself against —a sometimes severe immune response unfolds.

The CARPA-phenomenon (Complement Activation-Related PseudoAllergy) is a frequent hypersensitivity response to nanomedicine application. Up to 100 patients worldwide suffer from severe reactions, such as cardiac distress, difficulty of breathing, chest and back pain or fainting each day when their blood gets exposed to certain nanoparticles during medical treatment. Every 10 days one patient even dies due to an uncontrollable anaphylactoid reaction.

Apart from being activated in a different way, this pseudoallergy has the same symptoms as a common allergy, bearing a crucial difference:  the reaction is taking place without previous sensitizing exposure to a substance, making it hard to predict, whether a person will react to a specific nanodrug or be safe. Intrigued by this vital challenge, János Szebeni from Semmelweis University, Budapest, has been working with scientific verve on the decipherment and prevention of the CARPA phenomenon for more than 20 years. With his invaluable support De Gruyter´s European Journal of Nanomedicine (EJNM) lately dedicated an elaborate compilation of the most recent scientific advances on CARPA, presented by renowned experts on the subject.

A Feb. 23, 2016 De Gruyter Publishers press release, which originated the news item, provides more detail,

Interestingly it´s pigs that turned out to serve as best model for research on the complex pathomechanism, diagnosis and potential treatment of CARPA. “Pigs´ sensitivity equals that of humans responding most vehemently to reactogenic nanomedicines”, Szebeni states.  In a contribution to EJNM´s compilation on CARPA, Rudolf Urbanics and colleagues show that reactions to specific nanodrugs are even quantitatively reproducible in pigs … . Szebeni: “This is absolutely rare in allergy-research. In these animals the endpoint of the overreaction is reflected in a rise of pulmonary arterial pressure, being as accurate as a Swiss watch”. Pigs can thus be used for drug screening and prediction of the CARPAgenic potential of nanomedicines. This becomes increasingly important with the ever growing interest in modern drugs requiring reliable preclinical safety assays during the translation process from bench to bedside. Results might also help to personalize nanomedicine administration schedules during for example the targeted treatment of cancer. The same holds true for a very recently developed in vitro immunoassay. By simply using a patient´s blood sample, it tests for potential CARPA reactions even before application of specific nanodrugs.

Here’s a link to and a citation for the paper,

Lessons learned from the porcine CARPA model: constant and variable responses to different nanomedicines and administration protocols by Rudolf Urbanics, Péter Bedőcs, János Szebeni. European Journal of Nanomedicine. Volume 7, Issue 3, Pages 219–231, ISSN (Online) 1662-596X, ISSN (Print) 1662-5986, DOI: 10.1515/ejnm-2015-0011, June 2015

This paper appears to be open access.

As for reservations, I’m not sure what occasioned the news release so many months post publication of the paperand it should be noted that János Szebeni seems to be the paper’s lead author and the editor of the European Journal of Nanomedicine.

Short term exposure to engineered nanoparticles used for semiconductors not too risky?

Short term exposure means anywhere from 30 minutes to 48 hours according to the news release and the concentration is much higher than would be expected in current real life conditions. Still, this research from the University of Arizona and collaborators represents an addition to the data about engineered nanoparticles (ENP) and their possible impact on health and safety. From a Feb. 22, 2016 news item on phys.org,

Short-term exposure to engineered nanoparticles used in semiconductor manufacturing poses little risk to people or the environment, according to a widely read research paper from a University of Arizona-led research team.

Co-authored by 27 researchers from eight U.S. universities, the article, “Physical, chemical and in vitro toxicological characterization of nanoparticles in chemical mechanical planarization suspensions used in the semiconductor industry: towards environmental health and safety assessments,” was published in the Royal Society of Chemistry journal Environmental Science Nano in May 2015. The paper, which calls for further analysis of potential toxicity for longer exposure periods, was one of the journal’s 10 most downloaded papers in 2015.

A Feb. 17, 2016 University of Arizona news release (also on EurekAlert), which originated the news item, provides more detail,

“This study is extremely relevant both for industry and for the public,” said Reyes Sierra, lead researcher of the study and professor of chemical and environmental engineering at the University of Arizona.

Small Wonder

Engineered nanoparticles are used to make semiconductors, solar panels, satellites, food packaging, food additives, batteries, baseball bats, cosmetics, sunscreen and countless other products. They also hold great promise for biomedical applications, such as cancer drug delivery systems.

Designing and studying nano-scale materials is no small feat. Most university researchers produce them in the laboratory to approximate those used in industry. But for this study, Cabot Microelectronics provided slurries of engineered nanoparticles to the researchers.

“Minus a few proprietary ingredients, our slurries were exactly the same as those used by companies like Intel and IBM,” Sierra said. Both companies collaborated on the study.

The engineers analyzed the physical, chemical and biological attributes of four metal oxide nanomaterials — ceria, alumina, and two forms of silica — commonly used in chemical mechanical planarization slurries for making semiconductors.

Clean Manufacturing

Chemical mechanical planarization is the process used to etch and polish silicon wafers to be smooth and flat so the hundreds of silicon chips attached to their surfaces will produce properly functioning circuits. Even the most infinitesimal scratch on a wafer can wreak havoc on the circuitry.

When their work is done, engineered nanoparticles are released to wastewater treatment facilities. Engineered nanoparticles are not regulated, and their prevalence in the environment is poorly understood [emphasis mine].

Researchers at the UA and around the world are studying the potential effects of these tiny and complex materials on human health and the environment.

“One of the few things we know for sure about engineered nanoparticles is that they behave very differently than other materials,” Sierra said. “For example, they have much greater surface area relative to their volume, which can make them more reactive. We don’t know whether this greater reactivity translates to enhanced toxicity.”

The researchers exposed the four nanoparticles, suspended in separate slurries, to adenocarcinoma human alveolar basal epithelial cells at doses up to 2,000 milligrams per liter for 24 to 38 hours, and to marine bacteria cells, Aliivibrio fischeri, up to 1,300 milligrams per liter for approximately 30 minutes.

These concentrations are much higher than would be expected in the environment, Sierra said.

Using a variety of techniques, including toxicity bioassays, electron microscopy, mass spectrometry and laser scattering, to measure such factors as particle size, surface area and particle composition, the researchers determined that all four nanoparticles posed low risk to the human and bacterial cells.

“These nanoparticles showed no adverse effects on the human cells or the bacteria, even at very high concentrations,” Sierra said. “The cells showed the very same behavior as cells that were not exposed to nanoparticles.”

The authors recommended further studies to characterize potential adverse effects at longer exposures and higher concentrations.

“Think of a fish in a stream where wastewater containing nanoparticles is discharged,” Sierra said. “Exposure to the nanoparticles could be for much longer.”

Here’s a link to and a citation for the paper,

Physical, chemical, and in vitro toxicological characterization of nanoparticles in chemical mechanical planarization suspensions used in the semiconductor industry: towards environmental health and safety assessments by David Speed, Paul Westerhoff, Reyes Sierra-Alvarez, Rockford Draper, Paul Pantano, Shyam Aravamudhan, Kai Loon Chen, Kiril Hristovski, Pierre Herckes, Xiangyu Bi, Yu Yang, Chao Zeng, Lila Otero-Gonzalez, Carole Mikoryak, Blake A. Wilson, Karshak Kosaraju, Mubin Tarannum, Steven Crawford, Peng Yi, Xitong Liu, S. V. Babu, Mansour Moinpour, James Ranville, Manuel Montano, Charlie Corredor, Jonathan Posner, and Farhang Shadman. Environ. Sci.: Nano, 2015,2, 227-244 DOI: 10.1039/C5EN00046G First published online 14 May 2015

This is open access but you may need to register before reading the paper.

The bit about nanoparticles’ “… prevalence in the environment is poorly understood …”and the focus of this research reminded me of an April 2014 announcement (my April 8, 2014 posting; scroll down about 40% of the way) regarding a new research network being hosted by Arizona State University, the LCnano network, which is part of the Life Cycle of Nanomaterials project being funded by the US National Science Foundation. The network’s (LCnano) director is Paul Westerhoff who is also one of this report’s authors.

Harvard University’s Engineered Water Nanostructures (EWNS)

I last wrote about this research in a March 19, 2015 posting, which focused on work proving that a water-engineered nanostructure platform had microbial properties useful for decontaminating food and allowing manufacturers to avoid using chemicals for the task. This latest research focuses on finetuning the platform’s ability. Here’s more from the latest research paper’s abstract,

A chemical free, nanotechnology-based, antimicrobial platform using Engineered Water Nanostructures (EWNS) was recently developed. EWNS have high surface charge, are loaded with reactive oxygen species (ROS), and can interact-with, and inactivate an array of microorganisms, including foodborne pathogens. Here, it was demonstrated that their properties during synthesis can be fine tuned and optimized to further enhance their antimicrobial potential. A lab based EWNS platform was developed to enable fine-tuning of EWNS properties by modifying synthesis parameters. Characterization of EWNS properties (charge, size and ROS content) was performed using state-of-the art analytical methods. Further their microbial inactivation potential was evaluated with food related microorganisms such as Escherichia coli, Salmonella enterica, Listeria innocua, Mycobacterium parafortuitum, and Saccharomyces cerevisiae inoculated onto the surface of organic grape tomatoes. The results presented here indicate that EWNS properties can be fine-tuned during synthesis resulting in a multifold increase of the inactivation efficacy. More specifically, the surface charge quadrupled and the ROS content increased. Microbial removal rates were microorganism dependent and ranged between 1.0 to 3.8 logs after 45 mins of exposure to an EWNS aerosol dose of 40,000 #/cm3.

Here’s a link to and a citation for the paper,

Optimization of a nanotechnology based antimicrobial platform for food safety applications using Engineered Water Nanostructures (EWNS) by Georgios Pyrgiotakis, Pallavi Vedantam, Caroline Cirenza, James McDevitt, Mary Eleftheriadou, Stephen S. Leonard, & Philip Demokritou. Scientific Reports 6, Article number: 21073 (2016) doi:10.1038/srep21073 Published online: 15 February 2016

This is an open access paper.

No more kevlar-wrapped lithium-ion batteries?

Current lithium-ion batteries present a fire hazard, which is why, last, year a team of researchers at the University of Michigan came up with a plan to prevent fires by wrapping the batteries in kevlar. My Jan. 30, 2015 post describes the research and provides some information about airplane fires caused by the use of lithium-ion batteries.

This year, a team of researchers at Stanford University (US) have invented a lithium-ion (li-ion) battery that shuts itself down when it overheats, according to a Jan. 12, 2016 news item on Nanotechnology Now,

Stanford researchers have developed the first lithium-ion battery that shuts down before overheating, then restarts immediately when the temperature cools.

The new technology could prevent the kind of fires that have prompted recalls and bans on a wide range of battery-powered devices, from recliners and computers to navigation systems and hoverboards [and on airplanes].

“People have tried different strategies to solve the problem of accidental fires in lithium-ion batteries,” said Zhenan Bao, a professor of chemical engineering at Stanford. “We’ve designed the first battery that can be shut down and revived over repeated heating and cooling cycles without compromising performance.”

Stanford has produced a video of Dr. Bao discussing her latest work,

A Jan. 11, 2016 Stanford University news release by Mark Schwartz, which originated the news item, provides more detail about li-ion batteries and the new fire prevention technology,

A typical lithium-ion battery consists of two electrodes and a liquid or gel electrolyte that carries charged particles between them. Puncturing, shorting or overcharging the battery generates heat. If the temperature reaches about 300 degrees Fahrenheit (150 degrees Celsius), the electrolyte could catch fire and trigger an explosion.

Several techniques have been used to prevent battery fires, such as adding flame retardants to the electrolyte. In 2014, Stanford engineer Yi Cui created a “smart” battery that provides ample warning before it gets too hot.

“Unfortunately, these techniques are irreversible, so the battery is no longer functional after it overheats,” said study co-author Cui, an associate professor of materials science and engineering and of photon science. “Clearly, in spite of the many efforts made thus far, battery safety remains an important concern and requires a new approach.”

Nanospikes

To address the problem Cui, Bao and postdoctoral scholar Zheng Chen turned to nanotechnology. Bao recently invented a wearable sensor to monitor human body temperature. The sensor is made of a plastic material embedded with tiny particles of nickel with nanoscale spikes protruding from their surface.

For the battery experiment, the researchers coated the spiky nickel particles with graphene, an atom-thick layer of carbon, and embedded the particles in a thin film of elastic polyethylene.

“We attached the polyethylene film to one of the battery electrodes so that an electric current could flow through it,” said Chen, lead author of the study. “To conduct electricity, the spiky particles have to physically touch one another. But during thermal expansion, polyethylene stretches. That causes the particles to spread apart, making the film nonconductive so that electricity can no longer flow through the battery.”

When the researchers heated the battery above 160 F (70 C), the polyethylene film quickly expanded like a balloon, causing the spiky particles to separate and the battery to shut down. But when the temperature dropped back down to 160 F (70 C), the polyethylene shrunk, the particles came back into contact, and the battery started generating electricity again.

“We can even tune the temperature higher or lower depending on how many particles we put in or what type of polymer materials we choose,” said Bao, who is also a professor, by courtesy, of chemistry and of materials science and engineering. “For example, we might want the battery to shut down at 50 C or 100 C.”

Reversible strategy

To test the stability of new material, the researchers repeatedly applied heat to the battery with a hot-air gun. Each time, the battery shut down when it got too hot and quickly resumed operating when the temperature cooled.

“Compared with previous approaches, our design provides a reliable, fast, reversible strategy that can achieve both high battery performance and improved safety,” Cui said. “This strategy holds great promise for practical battery applications.”

Here’s a link to and a citation for the paper,

Fast and reversible thermoresponsive polymer switching materials for safer batteries by Zheng Chen, Po-Chun Hsu, Jeffrey Lopez, Yuzhang Li, John W. F. To, Nan Liu, Chao Wang, Sean C. Andrews, Jia Liu, Yi Cui, & Zhenan Bao. Nature Energy 1, Article number: 15009 (2016) doi:10.1038/nenergy.2015.9 Published online: 11 January 2016

This paper appears to be open access.

Waterless, stinkfree toilets thanks to nanotechnology

A Jan. 7, 2016 article by Magda Mis for the Thomson Reuters Foundation focuses on an innovative approach to waste management (toilets) taken by researchers at Cranfield University (UK),

A toilet that does not need water, a sewage system or external power but instead uses nanotechnology to treat human waste, produce clean water and keep smells at bay is being developed by a British university.

The innovative toilet uses a rotating mechanism to move waste into a holding chamber containing nano elements. The mechanism also blocks odours and keeps waste out of sight.

“Once the waste is in the holding chamber we use membranes that take water out as vapour, which can then be condensed and available for people to use in their homes,” Alison Parker, lead researcher on the project, told the Thomson Reuters Foundation.

“The pathogens remain in the waste at the bottom of the holding chamber, so the water is basically pure and clean.”

It’s known as the (Cranfield) Nano Membrane Toilet (website here),

I winced a bit watching that as would, I imagine, any number of people living in one of Britain’s former colonies (Canada, India, Ghana, Nigeria, Jamaica, New Zealand, and others in what’s now known as the Commonwealth countries).

Getting back to the article, Cranfield participated in a Gates Foundation competition and won a grant to develop this toilet,

Cranfield University is developing the toilet as part of the global “Reinvent the toilet Challenge” launched by the Bill and Melinda Gates Foundation.

Parker said that despite “significant” interest from developed countries, the toilet is being designed with those in mind who have no access to adequate toilets.

Poor sanitation is linked to transmission of diseases such as cholera, diarrhoea, dysentery, hepatitis A, typhoid and polio, the WHO [World Health Organization] says.

Cranfield University says its toilet is designed for a household of up to 10 people and will cost just $0.05 per day per user.

 

Québec’s second edition of its Best Practices Guidance for Nanomaterial Risk Management in the Workplace

Lynn Bergeson’s Dec. 16, 2015 posting on Nanotechnology Now highlights Québec’s second edition of its guide to best practices for handling nanomaterials in the workplace,

On December 11, 2015, the Institut de recherche Robert-Sauvé en santé et en sécurité du travail (IRSST), a leading occupational health and safety research center in Canada, published the second edition of its Best Practices Guidance for Nanomaterial Risk Management in the Workplace.

… IRSST intends the Guidance to support the safe development of nanotechnologies in Québec by bringing together current scientific knowledge on hazard identification, strategies for determining nanomaterial levels in different work environments, risk assessment, and the application of various risk management approaches. IRSST states that the Guidance provides practical information and prevention tools for the safe handling of nanomaterials in laboratories and pilot plants, as well as industrial facilities that produce or incorporate them. The Guidance recommends a preventive approach designed to minimize occupational exposure to nanomaterials. According to IRSST, given the different exposure pathways, the many factors that can affect nanomaterial toxicity and the health risks, its approach “is essentially based on hazard identification, different risk assessment strategies and a hierarchy of control measures, incorporating knowledge specific to nanomaterials when available.” The second edition of the Guidance incorporates new information in the scientific literature. In addition, IRSST has included appendices describing initiatives in Québec workplaces; examples of at-risk situations described in the literature; preventive measures and data on their relative efficacy; and the implementation of measures to control exposure. ,,,

The Best Practices Guidance for Nanomaterial Risk Management in the Workplace can be found here on the IRSST website where you’ll also find this description,

Today’s nanotechnologies can substantially improve the properties of a wide range of products in all sectors of activity, from the manufacture of materials with ground-breaking performance to medical diagnostics and treatment—yet they raise major technological, economic, ethical, social and environmental questions. Some of the spinoffs we can expect include the emergence of new markets, job creation, improvements in quality of life and contributions to protection of the environment. The impact of nanotechnologies is already being felt in sectors as diverse as agroprocessing, cosmetics, construction, healthcare and the aerospace industry. Most universities in Québec and many research centres are working to design new applications. Many companies have projects in the start-up phase, while others are already producing nanomaterials or have incorporated them in their processes to improve product performance, a trend expected to accelerate over the coming years. These new developments, which could mean exposure of a growing number of workers to these infinitesimally small particles, are of particular concern to workers in industry and staff in research laboratories. It is estimated that in 2015 about 10% of manufacturing jobs worldwide will be associated with nanotechnologies, [emphasis mine] and more than 2,000 commercial products will contain nanomaterials.

Given our fragmentary knowledge of the health and safety risks for workers and the environment, the handling of these new materials with their unique properties raises many questions and concerns. In fact, many studies have already demonstrated that the toxicity of certain nanomaterials differs from that of their bulk counterparts of the same chemical composition. Nanomaterials enter the body mainly through inhalation but also through the skin and the GI tract. Animal studies have demonstrated that certain nanomaterials can enter the blood stream through translocation and accumulate in different organs. Animal studies also show that certain nanomaterials cause more inflammation and more lung tumours on a mass-for-mass basis than the same substances in bulk form, among many other specific effects documented. In addition, research has shown that the physicochemical characteristics of nanomaterials (size, shape, specific surface area, charge, solubility and surface properties) play a major role in their impact on biological systems, including their ability to generate oxidative stress. It is thus crucial that risks be assessed and controlled to ensure the safe handling of nanomaterials. As with many other chemicals, a risk assessment and management approach must be developed on a case-by-case basis.

There is still no consensus, however, on a measurement method for characterizing occupational exposure to nanomaterials, making quantitative risk assessment difficult if not impossible in many situations. As a result, a precautionary approach is recommended to minimize worker exposure. In Québec, the employer is responsible for providing a safe work environment, and preventive measures must be applied by employees. Accordingly, preventive programs that take into account the specific characteristics of nanomaterials must be developed in all work environments where nanomaterials are handled, so that good work practices can be established and preventive procedures tailored to the risks of the particular work situation can be introduced.

Fortunately, current scientific knowledge, though partial, makes it possible to identify, assess and effectively manage these risks. This best practices guide is meant to support the safe development of nanotechnologies in Québec by bringing together current scientific knowledge on hazard identification, strategies for determining nanomaterial levels in different work environments, risk assessment and the application of various risk management approaches. Some knowledge of occupational hygiene is required to use this guide effectively. Designed for all work environments that manufacture or use nanomaterials, this guide provides practical information and prevention tools for the safe handling of nanomaterials in laboratories and pilot plants as well as industrial facilities that produce or incorporate them. To be effective, risk management must be an integral part of an organization’s culture, and health and safety issues must be considered when designing the workplace or as far upstream as possible. This is crucial for good organizational governance. In practice, risk management is an iterative process implemented as part of a structured approach that fosters continuous improvement in decision-making and can even promote better performance. The purpose of this guide is to contribute to the implementation of such an approach to the prevention of nanomaterial-related risks only. Depending on the process, other risks (associated with exposure to solvents, gas, heat stress, ergonomic stress, etc.) may be present, but they are not addressed in this guide.

I wonder where they got these numbers, “It is estimated that in 2015 about 10% of manufacturing jobs worldwide will be associated with nanotechnologies, and more than 2,000 commercial products will contain nanomaterials.” Given that many companies don’t like to disclose whether or not they’re using nanomaterials and most countries don’t insist on an inventory (there are voluntary inventories, which generally speaking have not been successful), bringing me back to the question: where did these numbers come from?

As for the guide itself, Canadians have been very involved with the OECD (Organization for Economic Cooperation and Development) and its ‘nanomaterial safety’ working group and, I understand, have provided leadership on occasion. The guide, which is available in both French and English, is definitely worth checking out.