The International Organization for Standardization (ISO) has published standard ISO 20814:2019, “Nanotechnologies — Testing the photocatalytic activity of nanoparticles for NADH oxidation.” The standard specifies a method for the measurement of the photocatalytic activity (PCA) of nanoparticles (NP), suspended in an aqueous environment in physiologically relevant conditions, by measuring the ultraviolet (UV)-induced nicotine adenine dinucleotide hydrate (NADH) oxidation. According to ISO, the measurement is intended to assess the potential for the photo-toxicity of nanomaterials. The method is also applicable to NP aggregates and agglomerates. ISO states that existing standard test methods for particle and surface PCA measurement (see ISO 10676 and ISO 10678) are not directly applicable to determine nanomaterial PCA leading to photo-toxicity, as they require a large test volume and/or long measurement duration, while using organic dyes as indicators that are not biocompatible.
The Sustainable Nanotechnology Organization (SNO) and Nanotechnology, Occupational and Environmental Health (NanOEH) committees will host the 9th Nano Conference October 4-6, 2020. The Conference will address:
- Green/advanced synthetic materials and manufacturing;
- Nanomedicine, nanodrugs, and pharmaceutical and medical applications;
- Nanotoxicology related to humans;
- Occupational and environmental exposure assessment;
- Global challenges;
- Sustainable water treatment and remediation;
- Fate and transport;
- Sustainable food and agriculture;
- Sustainability and energy;
- Devices and sensors;
- Education panel; and
- Regulation and policy.
The Conference will be held in Denver, Colorado.
On December 5, 2019, the National Toxicology Program (NTP) announced that the NTP Technical Report on the Toxicity Studies of 1020 Long Multiwalled Carbon Nanotubes Administered by Inhalation to Sprague Dawley (Hsd:Sprague Dawley® SD®) Rats and B6C3F1/N Mice is now available. In 2003, the Rice University Center for Biological and Environmental Nanotechnology nominated nanoscale materials as a class of substances for toxicological evaluation. The recommended studies included “[c]haracteriz[ing] the inhalation toxicology of high aspect ratio materials, such as carbon nanotubes (single-walled or multi-walled), as a function of material purity and stabilization.” According to the abstract for the Technical Report, “[b]ecause long-term inhalation toxicity and carcinogenicity studies were being conducted on a relatively short, rigid [multiwalled carbon nanotube (MWCNT)], a representative long and thin MWCNT was selected for these studies.” Following an evaluation of 24 different long, thin MWCNTs, NTP selected the 1020 Long Multiwalled Carbon Nanotube (L-MWNT-1020) (Sun Innovations, Fremont, CA) “based on availability, high purity (97%), and the low amount of residual nickel catalyst (0.52% by weight).” The abstract states that 0.3 milligrams per cubic meter (mg/m3) is considered the no‑observed‑adverse‑effect level (NOAEL) for L-MWNT-1020. The Technical Report notes that the exposure concentrations used in the study were approximately 100-fold higher than the National Institute for Occupational Safety and Health (NIOSH)-proposed recommended exposure limit (REL) for carbon nanotubes (CNT) of 1.0 micrograms per cubic meter (μg/m3) elemental carbon as a respirable mass eight-hour time-weighted average (TWA) concentration. According to the Technical Report, “NIOSH researchers have also evaluated exposure in multiple U.S. manufacturers of CNTs and nanofibers and reported inhalable exposures of MWCNT of up to 0.4 mg/m3.” The Technical Report states that given the long half-life and persistence of MWCNT in the lung, “even short periods of exposure at such levels would lead to chronic high-level exposures. Therefore, although the no-observed-adverse-effect level determined in the present study (0.3 mg/m3) is approximately 300-fold higher than the recommended exposure limit, it is within the range observed in occupational settings and may be informative regarding potential health risks associated with occupational exposures to CNTs.” The abstract includes a detailed chart summarizing the findings considered to be toxicologically relevant in rats and mice exposed to L-MWNT-1020 by inhalation for 30 days.
On November 25, 2019, the European Union (EU) Observatory for Nanomaterials (EUON) announced the publication of a study published in Frontiers in Pharmacology entitled “Unpredictable Nanoparticle Retention in Commonly Used Plastic Syringes Introduces Dosage Uncertainties That May Compromise the Accuracy of Nanomedicine and Nanotoxicology Studies.” The researchers in the study radiolabeled a variety of different nanoparticles, loaded suspensions of particles into different plastic syringes, and then measured the radioactivity left behind after emptying the nanoparticle suspension from the syringe. This provided a simple way to measure the fraction of nanoparticles that remained stuck inside the syringe. According to EUON, in the worst case, up to 79.1 percent of the nanoparticles remained. The study found variability in the amounts remaining behind depending on the types of particles and syringes used. The researchers propose checks to determine the correct combination of syringe and nanoparticle that should be used to minimize the problem. The study did not identify the root causes of the high variability between the different nanoparticles and syringe types used.
The European Chemicals Agency (ECHA) announced on December 3, 2019, that it has developed a new Appendix for nanoforms applicable to the Guidance on Registration and Substance Identification. According to ECHA, it aligns ECHA’s guidance with the amended annexes of the Registration, Evaluation, Authorization and Restriction of Chemicals (REACH) regulation that will apply to nanomaterials and enter into force on January 1, 2020. The new guidance document explains the term nanoform, provides advice on how to build and justify sets of nanoforms, and explains what characterization information needs to be reported. ECHA updated the Appendix for nanoforms applicable to the Guidance on QSARs and Grouping of Chemicals to reflect the advice of the new guidance document. ECHA states that the update also clarifies the differences between creating a set of nanoforms and read-across for justifying the use of hazard data between different (sets of) nanoforms of a substance. ECHA notes that it will keep updating the existing guidance for human health and environmental information requirements during 2020. To support potential registrants in meeting the new information requirements, an updated overview of available test guidelines and other recognized methods and standards is available on the European Union Observatory for Nanomaterials (EUON)
The European Commission’s Joint Research Center (JRC) recently published a white paper entitled Anticipation of regulatory needs for nanotechnology-enabled health products. The white paper notes that at this time, “no specific regulatory framework exists for nanotechnology-enabled health products but the current regulatory practice requires additional guidance in order to fully cover the particularities of such products.” The white paper identifies the following major challenges associated with regulating nanotechnology-enabled health products:
- Depending on their mode of action, nanotechnology-enabled health products are regulated either as medicinal products or medical devices. Due to the increased complexity of such products and their size-related properties, the selection of the regulatory path may be challenging since the primary mode of action might be difficult to determine.
- Due to the rapid progress in the field and the lack of robust data sets, only limited guidance on regulatory information needs is currently available, and the question remains whether the identified requirements in this initial guidance are sufficient for a reliable characterization and assessment of all nanotechnology-enabled health products. To generate the required information on the quality, safety, and efficacy of the products, standardized testing methods have to be available.
- As patents expire for certain nanomedicinal products, generic versions of the innovator products will require access to the market. Since the physicochemical characteristics can be very complex for nanotechnology-enabled products and achieved through sophisticated manufacturing processes, the current regulatory practice to assess the equivalence of the products may not be sufficient. More guidance is needed on how the similarity of follow-on products can be demonstrated and suitable standardized methods assessing the (bio) equivalence of such products need to be developed.
- The European Union (EU) definition of nanomaterials will apply for nanotechnology-enabled medical devices, outlining their classification and regulatory requirements. The implementation of the definition and the classification rule, introducing the need to define the internal exposure to nanomaterials, pose additional challenges, however.
The white paper states that the regulatory challenges it highlights “should guide the research projects and the involved communities willing to advance the regulatory science in the area of nanotechnology-enabled health products.”
The International Chemical Secretariat (ChemSec) announced on November 14, 2019, that it added more chemicals, including carbon nanotubes, to its Substitute It Now! (SIN) List. ChemSec describes carbon nanotubes as “one of the more well-studied nanomaterials” and notes that “they are used to make durable, lightweight materials, for electrical conductivity, as a super black pigment and for water purification, among other uses.” Dr. Anna Lennquist, Project Manager for the SIN List at ChemSec, states: “Several studies have shown that carbon nanotubes cause lung cancer. The small tubes induce inflammation in a somewhat similar way to asbestos. Reprotoxic properties have also been observed. Up until now, the debate about the safety of nano has focused on the fact that more research is needed. However, here is a perfect example of where there is enough science to say that these materials should not be used.” ChemSec’s questions and answers (Q&A) regarding the SIN List include the following Q&A:
Why have you only decided to include carbon nanotubes? What about other nanomaterials?
For anything we put on the SIN List, we need to be able to defend our decision to call this a Substance of Very High Concern. This means that we both need to be scientifically certain about the hazardous properties and also that the hazardous properties need to correspond to the REACH SVHC criteria and be relevant for regulation. Another reason for only including carbon nanotubes is that we, today, unfortunately do not have enough data on hazardous properties for many nanomaterials.
Anna Lennquist, Senior Toxicologist at ChemSec
The U.S. Environmental Protection Agency (EPA) issued final significant new use rules (SNUR) on November 25, 2019, for 22 chemical substances, including carbon nanomaterial (generic) (PMN P-10-366), that are the subject of premanufacture notices (PMN). 84 Fed. Reg. 64754. Persons who intend to manufacture (defined by statute to include import) or process any of these chemical substances for an activity that is designated as a significant new use by the SNURs to notify EPA at least 90 days before commencing that activity. Persons may not commence manufacture or processing for the significant new use until EPA has conducted a review of the notice, made an appropriate determination on the notice, and has taken such actions as are required by that determination. The final SNURs will be effective on January 24, 2020.
The requirements of the final SNUR for carbon nanomaterial (generic) (PMN P-10-366) do not apply to quantities of the substance after they have been reacted (cured), incorporated, or embedded into a polymer matrix that itself has been completely reacted (cured), embedded in a permanent solid polymer, metal, glass, or ceramic form, or completely embedded in an article as defined at 40 C.F.R. Section 720.3(c). The significant new uses are:
- Protection in the workplace. Requirements as specified in Section 721.63(a)(1), (a)(2)(i) and (ii), (a)(3) through (5) (respirators must provide a National Institute for Occupational Safety and Health certified air purifying, tight-fitting full-face respirator equipped with N-100, P-100, or R-100 filter with an Assigned Protection Factor of at least 50), (a)(6) (particulate (including solids or liquid droplets)), (when determining which persons are reasonabl[y] likely to be exposed as required for Section 721.63(a)(1) and (4) engineering control measures (e.g., enclosure or confinement of the operation, general and local ventilation) or administrative control measures (e.g., workplace policies and procedures) shall be considered and implemented to prevent exposures, where feasible), and (c).
- Industrial, commercial, and consumer activities. Requirements as specified in Section 721.80(k), (l), (q), and (y)(1) (when the substance is in liquid resin form). It is a significant new use to process or use the powder form of the substance outside of the site of manufacture or processing.
- Release to water. Requirements as specified in Section 721.90(a)(1), (b)(1), and (c)(1).
On November 22, 2019, the European Commission (EC) Directorate-General for Internal Market, Industry, Entrepreneurship, and Small- and Medium-Sized Enterprises (SME) requested two scientific opinions from the Scientific Committee on Consumer Safety (SCCS):
- Request for a scientific opinion on platinum (nano)-colloidal platinum (nano) (Chemical Abstracts Service (CAS) No. 7440-06-4, EC No. 231-116-1) and acetyl tetrapeptide-17 colloidal platinum (nano) (CAS and EC Nos. not available); and
- Request for a scientific opinion on gold (nano)-colloidal gold (nano) (CAS No. 7440-57-5, EC No. 231-165-9), gold thioethylamino hyaluronic acid (nano) (CAS No. 1360157-34-1, EC No. not available), and acetyl heptapeptide-9, colloidal gold (nano) (CAS and EC Nos. not available).
The request for a scientific opinion on platinum (nano)-colloidal platinum (nano) and acetyl tetrapeptide-17 colloidal platinum (nano) states that the EC received 18 notifications for cosmetic products containing platinum (10 notifications) and colloidal platinum (8 notifications) (CAS No 7440-06-4, EC No. 231-116-1) in nano form. The EC received 13 notifications for cosmetic products containing acetyl tetrapeptide-17 colloidal platinum (CAS and EC Nos. not available) in nano form. The EC states that it has concerns on the use of platinum-colloidal platinum and acetyl tetrapeptide-17 colloidal platinum in nano form because of the potential for nanoparticles to be absorbed dermally or across a mucous membrane and to enter cells.
The request for a scientific opinion on gold (nano)-colloidal gold (nano), gold thioethylamino hyaluronic acid (nano), and acetyl heptapeptide-9, colloidal gold (nano) states that the EC received 236 notifications for cosmetic products containing gold (68 notifications) and colloidal gold (168 notifications) (CAS No. 7440-57-5, EC No. 231-165-9) in nano form. The EC received 11 notifications for cosmetic products containing gold thioethylamino hyaluronic acid (CAS No. 1360157-34-1, EC No. not available) in nano form. The EC received 18 notifications for cosmetic products containing acetyl heptapeptide-9, colloidal gold (CAS and EC Nos. not available) in nano form. The EC states that it has concerns on the use of gold-colloidal gold, gold thioethylamino hyaluronic acid, and acetyl heptapeptide-9, colloidal gold in nano form because of the potential for nanoparticles to be absorbed dermally or across a mucous membrane and to enter cells.
The deadline for each opinion is six months from receipt. SCCS adopted the mandates at its October 30-31, 2019, plenary meeting.
The National Nanotechnology Initiative (NNI) announced on November 19, 2019, the launch of the Nanotechnology Entrepreneurship Network (NEN), “a new community of interest to support entrepreneurs interested in commercializing nanotechnologies.” According to NNI, NEN will bring new and seasoned entrepreneurs together with the people and resources available to support them. NNI states that NEN will provide a forum for sharing best practices for advancing nanotechnology commercialization and the lessons learned along the technology development pathway. Activities are likely to include a monthly podcast series, webinars, workshops, and town hall discussions. The inaugural podcast in the series features a conversation between National Nanotechnology Coordination Office (NNCO) Director Lisa Friedersdorf and Joe Sprengard, Chief Executive Officer and founder of Veelo Technologies, who discusses his journey as an entrepreneur and shares the advice he received when he was getting started.