The European Chemicals Agency (ECHA) announced in its February 1, 2023, ECHA Weekly that it has released an updated appendix for nanomaterials that provides guidance on how to obtain data under the new information requirements for nanoforms. According to ECHA, this includes information on how to perform environmental testing and advice on preparation methods and testing strategies for physico-chemical testing of nanoforms. ECHA notes that the Partner Expert Group (PEG) members “actively contributed to the update.” The changes to Guidance on information requirements and chemical safety assessment: Appendix R7-1 for nanomaterials applicable to Chapter R7a Endpoint specific guidance include:

  • Update of the advisory note on testing and sampling strategy and sample preparation for ecotoxicological endpoints:
  • Update and revision of Section 1.1 and subsections with 1.1.1. Characterisation of test materials, 1.1.2 Sample preparation of test materials, and 1.1.3 General considerations for Fate and (Eco)-Toxicological testing; and
  • Update of Glossary Section;
  • Update of Section 1 for water solubility, granulometry, n-octanol/water partition coefficient (Kow), adsorption/desorption:
  • Addition of subsection for Section 1.2.1 Water solubility with waivers and dissolution rate;
  • Addition of subsection for Section 1.2.2 Partition coefficient n-octanol/water, with waivers and dispersion stability;
  • Addition of subsection for Section 1.2.4 Dustiness; and
  • Addition of subsection for Section 1.2.5 Adsorption/Desorption with waivers and alternative methods to organic carbon-water partition coefficient (Koc).

On January 17, 2023, the European Union (EU) Observatory for Nanomaterials (EUON) published a Nanopinion entitled “EU 2025: Enjoying the Benefits of Nanotechnology and NMS” by Dr. Anastasios Papadiamantis and Dr. Antreas Afantitis, both of NovaMechanics Ltd. The authors report the findings of a study commissioned by EUON on the EU market for nanomaterials, including substances, uses, volumes, and key operators. The authors state that the EU (including the European Economic Area (EEA) countries and Switzerland) nanomaterials market “is expected to have a steady growth led by the medicine and personal care and manufacturing sectors.” The projected compound annual growth rate until 2025 is 13.9 percent per volume and 18.4 percent per value driven by technological advancement and strong consumer demand. The authors note that “the recent events in Ukraine add yet another barrier to the already existing relatively high barriers to enter the market, such as a strict regulatory landscape, the high power of suppliers and tough competition.” More information and an in-depth analysis are available in the full report as prepared by NovaMechanics Ltd and published by the European Chemicals Agency (ECHA).

The Organization for Economic Cooperation and Development (OECD) will hold a webinar on February 7, 2023, on Test Guideline (TG) No. 125: Nanomaterial Particle Size and Size Distribution of Nanomaterials. OECD states that it will present the methods described in TG No. 125 to determine the size and size distributions of nanomaterial particles and fibers spanning from one nanometer (nm) to 1,000 nm. During the webinar, attendees will be able to learn the use and limitation of the TG, as well as of the validation exercise that was done to support its development. OECD is organizing the webinar to increase awareness of this newly adopted TG. According to the preliminary agenda, the webinar will cover:

  • TGs at OECD;
  • Introduction and background for developing TG 125;
  • Overview and general messages;
  • Methods for particle measurements;
  • Methods for fiber measurements; and
  • Summary and questions and answers.

Registration is open.

L’association de veille et d’information civique sur les enjeux des nanosciences et nanotechnologies (AVICENN), a French non-governmental organization (NGO), announced on December 15, 2022, publication of a report entitled Searching for [Nanos] in Everyday Products. AVICENN sought to obtain an “overview of ‘nano impregnation’ in everyday consumer products in 2021-2022.” AVICENN selected products from categories already tested (food products, cosmetics, and medicines) to determine if any change was found and products where the presence of nanomaterials was suspected but not previously publicly tested (hygiene products, toys, clothing, and packaging). Because of the expense of testing, AVICENN states that it had to limit its investigation to 23 products. AVICENN acknowledges that its investigation “is therefore by nature qualitative and does not claim to be exhaustive or representative.” AVICENN reports that it found nanomaterials in 20 products in the cosmetics, hygiene and health, food, toys, and paint categories. AVICENN states that its results show the “failure” of [nano] labeling, given that most of the products in which it detected nanomaterials are covered by the European Union’s (EU) “nano” labeling requirements for cosmetics, food products, and biocidal products. According to AVICENN, the presence of nanomaterials in other product categories highlights the need to extend the [nano] labeling requirements to other product categories.

On November 25, 2022, the Swedish National Platform for Nanosafety (SweNanoSafe) and the Swedish University of Agricultural Sciences (SLU) held the Fifth Annual Research Network Workshop. According to SweNanoSafe’s December 20, 2022, announcement, the online workshop was chaired by Geert Cornelis and attracted some 40 participants. SweNanoSafe has posted an overview of the workshop contents that includes a summary of the key outcomes. According to the report, the breakout sessions identified difficulties in current research and future challenges:

  • From the breakout session on measurements, the two main points concerned analytical challenges and information sharing or transfer. Materials expected to be relevant in the future, such as silicon carbide and graphene, “pose analytical challenges and are difficult to measure with currently available techniques.” Open data and information sharing was also noted as a challenging area.
  • The breakout session on exposure highlighted several knowledge gaps connected to understanding and modeling the environmental fate of advanced materials. According to the report, “[a] major challenge is to ascertain what organisms truly are exposed to, in the environment as well as our testing systems.” There is also the question of transformation and its reversibility in different uses and life cycles. Advanced materials consist of multiple compounds, posing challenges to understanding processes affecting fate and toxicity.
  • During the breakout session on effects, the discussions connected to the issues of the definition of advanced materials and communication. To date, there is no clear and broadly agreed upon definition of advanced materials, nor is there an agreement on whether the focus of such a definition should be on the material or on the advanced function. It can furthermore be questioned whether the term advanced materials is relevant in the context of hazard assessment. Developing new approaches to hazard assessment and the use of non-standard data will require communication with regulators, and researchers and regulators need to understand each other’s viewpoints to make progress in this area.

According to SweNanoSafe, the slides from the presentations will be available shortly.

On February 1, 2023, the National Nanotechnology Initiative (NNI) will hold a webinar on the environmental, health, and safety (EHS) implications of metal nanoparticles in aquatic environments. According to NNI, the focus will be on copper and copper oxide, nickel, and silver nanoparticles. Each expert panelist will provide an overview on the current state of knowledge for a particular metal nanoparticle. The panelists will discuss methods used for identifying, measuring, and assessing the potential effects of the metal nanoparticle in aquatic environments. Jim Dobrowolski, National Program Leader, National Institute for Food and Agriculture (NIFA), United States Department of Agriculture (USDA), will moderate the panel, which will include:

  • Stacey Harper, Professor, Department of Environmental and Molecular Toxicology, Oregon State University;
  • Custodio Muianga, Environmental Health Scientist, Agency for Toxic Substances and Disease Registry (ATSDR)/National Center for Environmental Health (NCEH), Centers for Disease Control and Prevention (CDC); and
  • Olga Tsyusko, Associate Professor, Department of Plant and Soil Sciences, University of Kentucky.

Registration is now open.

On December 20, 2022, the European Union (EU) Observatory for Nanomaterials (EUON) published a Nanopinion entitled “Controlling Exposure to Nanomaterials” by Dr Araceli Sánchez, Spanish Institute of Health and Safety (INSST). Sánchez notes that over the last 15 years, scientists have paid attention to the development of new instruments capable of measuring personal exposure to nanosize particles, and new frameworks, methodologies, and standards to assess and control exposure to engineered nanomaterials in the workplace have been published. According to Sánchez, since 2007, some institutions, such as the United Kingdom’s (UK) British Standards Institution (BSI), the U.S. National Institute for Occupational Safety and Health (NIOSH), the German Institute of Occupational Safety and Health (IFA), and the Dutch government started to recommend pragmatic “benchmark exposure levels” to control workplace exposures to nanomaterials. Sánchez states that this “undoubtedly” was a necessary measure to minimize exposure. The benchmark values were developed following different approaches (Mihalache et al. 2016), however, and “with the exception of those proposed by NIOSH,” do not represent health-based occupational exposure limits (OEL). Health-based inhalation OELs are time-weighted average (typically eight-hour) air concentrations believed to represent a safe level of exposure for most workers over their working lifetime. Benchmark values are cautious levels to prevent exposure, but do not represent safe levels to which workers can be exposed without developing adverse health effects. Sánchez states that some advances on this front have been published recently, such as Visser et al. (2022), which provides recommendations from an expert panel to establish health-based nano reference values differentiating six groups of engineered nanomaterials.

The Organization for Economic Cooperation and Development has published a draft Study Report on Applicability of the key event based TG 442D for in vitro skin sensitisation testing of nano-materials. The study summary and conclusions include the following questions and answers (Q&A):

  • Is the Test Guideline (TG) technically applicable?
Yes, OECD TG 442D (KeratinoSensTM test method) is from a technical point of view applicable for the testing of manufactured nanomaterials. The draft report notes that it was not possible to make any assumption about the relevance for the in vivo correlation due to the scarce availability of data for manufactured nanomaterials that have been tested in vivo. Nevertheless, the work conducted within this project can be seen as a starting point for further work with regard to manufactured nanomaterials safety testing for skin sensitization.

 

  • Which nanomaterials are suitable for testing?
Different manufactured nanomaterials were selected for testing based on an extensive literature review and dependent on information about their skin sensitizing potential. In total, 12 inorganic and organic manufactured nanomaterials were selected (nine test materials, three controls). Testing with KeratinoSensTM was from a technical point of view possible with all of the selected manufactured nanomaterials.

 

  • Are there nanomaterials that were not possible to test?
During the practical part of this study, there were no manufactured nanomaterials identified that could not be tested. The draft study notes that the sample number of 12 manufactured nanomaterials is relatively small in comparison to the variety of manufactured nanomaterials, however, and the authors cannot conclude whether there is one manufactured nanomaterials group that cannot be tested using KeratinoSensTM. According to the draft study, the critical step might be the sample preparation. If a manufactured nanomaterial cannot be dispersed to be tested in the respective media for KeratinoSensTM, it cannot be tested in this assay.

 

  • What has to be adapted to use the TG for nanomaterials?
According to the experience gained during the testing of selected manufactured nanomaterials with the KeratinoSensTM and based on the discussion within the two expert workshops in December 2019 and 2021, some recommendations can be made with regard to the dispersion protocols, needs for endotoxin assays, potential to include leaching experiments, and the role of dimethyl sulfoxide (DMSO) as a mediator to assist nanomaterial penetration into cells. Further, the potential for nanomaterials to interact with detection methodologies also brought in the possibility to use two different colorimetric cytotoxicity assays.

 

  • Are protocol changes needed to test nanomaterials?

Some of the recommendations made under the previous point can be directly addressed by adaptation of the standard operating procedures (SOP) of the KeratinoSensTM test method, e.g., viability assessment.

 
Comments are due January 31, 2023.

As reported in our October 19, 2021, blog item, in 2021, the French Agency for Food, Environmental and Occupational Health and Safety (ANSES) released a scientific guide to assess the risks posed by nanomaterials in food. On December 16, 2022, ANSES announced that the methodology has been “tested” on the food additive E171, titanium dioxide. ANSES states that the test has “confirmed the relevance of [its] methodology and the need for a nanospecific approach.” According to ANSES, the methodology enabled it to calculate exposure levels for different populations and identify several potential health effects. ANSES notes that it was not possible to complete the risk assessment of the additive E171 because some data were missing. Based on its findings, ANSES “reiterat[es] its recommendation to limit exposure of workers and consumers to nanomaterials until their safety can be demonstrated, and avoid the dispersal of these particles in the environment. To this end, the Agency recommends promoting the use of products that do not contain nanomaterials and are equivalent in terms of function, effectiveness and cost.”

ANSES states that it will work with its counterparts, in particular the European Food Safety Authority (EFSA), to advance risk assessment methodologies and harmonize testing protocols for the physico-chemical characterization and toxicology of nanomaterials. In 2018, EFSA published a guide to assessing dossiers on nanoscience and nanotechnologies in applications such as food additives, pesticides, and food contact materials. According to ANSES, although the methodologies developed by EFSA and ANSES are based on similar concepts and risk assessment methodologies, ANSES’ approach proposed specific adaptations related to regulatory definitions of nanomaterials, particle size measurements, dissolution properties, and hazard identification

The Australian Industrial Chemicals Introduction Scheme (AICIS) posted a news item on December 19, 2022, reminding assessment certificate applicants that extra information is required for chemicals at the nanoscale. AICIS has published extra guidance on the data concerning the nanoscale-specific physicochemical properties that must be provided. AICIS states that nanoscale means a particle size range of one to 100 nanometers (nm). An introduction at the nanoscale is a “specified class of introduction” if the substance:

  • Is introduced as a solid or is in a dispersion; and
  • Consists of particles in an unbound state or as an aggregate or agglomerate, where at least 50 percent (by number size distribution) of the particles have at least one external dimension in the nanoscale.

If the chemical is at the nanoscale and is categorized as an assessed introduction, information about the chemical’s identity and physicochemical properties must be provided, including:

  • Shape of the particle;
  • Particle size and particle size distribution (PSD);
  • Volume-specific surface area;
  • Surface chemistry — the chemical nature of the surface of a particle;
  • Surface charge;
  • Measured data describing dispersibility (if relevant and information is available);
  • Measured data on particle concentration;
  • Measured data describing dustiness (only required if inhalation exposure is likely to occur);
  • Measured data or suitable alternatives describing the biological (re)activity;
  • Data on photoreactivity (if relevant); and
  • Human health hazards.

AICIS notes that all Organization for Economic Cooperation and Development (OECD) Test Guidelines available for testing human health toxicity endpoints are considered applicable in the absence of equivalent testing guidelines for nanoscale chemicals.