The Nanotechnology Industries Association (NIA) will hold a webinar on July 7, 2020, on “Introducing the NanoHarmony project.” Funded through Horizon 2020, NanoHarmony began on April 1, 2020. NanoHarmony brings together 14 expert partners from ten European countries and will work alongside the Organization for Economic Cooperation and Development (OECD) and European Chemicals Agency (ECHA) to support the development of test guidelines and guidance documents for eight endpoints where nanomaterial-adapted test methods have been identified as an industrial priority. NanoHarmony will coordinate the collection and use of available data and information to support the development of test methods and to organize a sustainable network for the needed exchange, as well as for future regulatory development needs. NanoHarmony is coordinated by the German Federal Institute of Occupational Safety and Health (BAuA). Partners include the Dutch National Institute for Public Health and the Environment (RIVM), the United Kingdom’s (UK) Department of Health, the Luxembourg Institute of Science and Technology, NIA, the University of Plymouth, the National Research Center for the Working Environment (NRCWE), the French National Institute for Industrial Environment and Risks (INERIS), the Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA), the Istituto Superiore di Sanità, the UK Center for Ecology and Hydrology (UKCEH), the University of Aveiro, BASF, and the German Federal Institute for Risk Assessment (BfR). Bergeson & Campbell, P.C. is a proud NIA member.
As reported in our April 8, 2020, blog item, the National Academies of Sciences, Engineering, and Medicine (National Academies) published a prepublication copy of A Quadrennial Review of the National Nanotechnology Initiative: Nanoscience, Applications, and Commercialization. The National Nanotechnology Coordination Office (NNCO) asked the National Academies to form an ad hoc committee to conduct a quadrennial review of the National Nanotechnology Initiative (NNI) pursuant to the 2003 21st Century Nanotechnology Research and Development Act, which authorized the NNI to coordinate the nanotechnology-related research and development (R&D) of 26 federal agencies. On June 9, 2020, from 1:00 p.m.-2:30 p.m. (EDT), the National Academies will hold a report briefing webinar featuring its report, A Quadrennial Review of the National Nanotechnology Initiative. During the webinar, members of the ad hoc committee will discuss how U.S. nanotechnology programs compare to those in other nations, whether coordination under the NNI should continue, and how to improve the NNI’s R&D strategy to enhance further U.S. economic prosperity and security. Speakers will take questions from the audience.
On May 26, 2020, the European Union (EU) NanoSafety Cluster announced the publication of the final report of the (nano) TiO2 safety communication Task Force. The goal of the task force was to provide scientific input to the ongoing classification of titanium dioxide (TiO2). The Task Force ran from January 2018 to January 2019, collecting information regarding the classification of TiO2 and information on TiO2 hazard potential from available scientific literature. According to the final report, to understand and document the current state of the science on lung particle overload, a workshop was held in Edinburgh, Scotland, in April 2019 to solicit opinions from an Expert Panel on the definition of poorly soluble, low-toxicity particles (PSLT); lung particle overload; and, the human relevance of the rat lung response. The final report states that the Expert Panel on PSLTs provided important guidance for conducting and interpreting PSLT inhalation toxicology studies. Task Force members suggest that the final paper and the expert opinion from the PSLT workshop be used as relevant scientific documents when communicating about PSLT inhalation toxicity. Given the ongoing discussion on the classification and safety of other PSLTs, the final paper states that “it would be important to re-activate the public debate including experts and stakeholders.” The final paper notes that there “is even a lack of a clear definition of PSLTs.” The final paper concludes that an open discussion would serve to document formally where scientific consensus and differences exist and could form the basis for the design of future safety assessments and decisions.
The European Union (EU) Observatory for Nanomaterials (EUON) announced on May 20, 2020, that a recent study has analyzed existing research on whether nanomaterials used in consumer products and at workplaces are absorbed through the skin. The study was commissioned by EUON and carried out by the RPA consortium of Triskelion and the Dutch National Institute for Public Health and the Environment (RIVM). According to EUON, the study found that the lack of standardized, validated methods and the use of varying testing protocols make it difficult to compare results and evaluate whether nanomaterials can penetrate the skin. EUON states that “[b]ased on the findings, nanomaterials rarely absorb through intact skin, except for silver that is likely to partly penetrate in ionic form. Silver is used for its anti-bacterial properties in textiles and can be found in other consumer products such as pharmaceuticals and cosmetics.” Some of the analyzed studies suggest that absorption through damaged skin is higher than through intact skin. EUON notes that a key recommendation for any new studies that aim to provide proof of skin absorption is to perform them using tests performed on tissue in external environments with minimal alterations to natural conditions (ex vivo), comparable to the Organization for Economic Cooperation and Development (OECD) Test Guideline 428, with human or porcine skin. EUON states that rodent skin should not be used due to differences in skin characteristics between rodents and humans.
The study covered experimental data, including tests performed inside the bodies of living organisms (in vivo) and ex vivo studies. It looked at factors associated with test methodology that can affect absorption through the skin, for example: exposure conditions; different experimental set-ups; and methods. The effects of the characteristics of nanomaterials on skin absorption, including particle size and surface charge, were also analyzed. According to EUON, in addition to compiling relevant studies, the study looked at test guidelines and whether the results are available in a structured way, for example, following OECD harmonized templates.
On April 12, 2020, the World Health Organization (WHO) published Environmental Health Criteria 244: Principles and methods to assess the risk of immunotoxicity associated with exposure to nanomaterials. WHO states that the document presents an overview of the current knowledge and evidence on principles and basic mechanisms of immunotoxicity caused by engineered nanomaterials (ENM). The document provides guidance on principles and methods for hazard and risk assessment of different ENMs and groups of ENMs on the immunological system in the body; describes the key cell types and elements and the functioning of the human immunological system; and provides information on the effects of various ENMs on these cells and elements of the immune system. It includes case studies on carbon nanotubes and silver nanoparticles to illustrate how the information derived from the application of currently available methods can be structured to assess the hazards in terms of their immunotoxic properties. The document includes the following recommendations:
- Include nanoimmunotoxicity risk assessment in general nanotoxicity risk assessment;
- Define the minimal requirements for characterization of test materials before, during, and after the experiments, and control the dispersion of ENMs for both in vivo and in vitro testing;
- Define reference materials for further testing, standardization, and validation of test systems;
- Advance testing for effects of nanomaterials by implementing developments in the fields of molecular biology, systems biology, bioinformatics, high-throughput screening, and in silico modeling;
- Validate test methods for ENMs by ensuring that the test material itself does not interfere with the assay, and establish validated protocols for endotoxin testing of ENMs;
- Advance approaches to relevant exposure regimens, both in vivo and in vitro, and define the most appropriate dose metrics (particle mass, number, surface area);
- Identify positive controls for various bioassays;
- Explore absorption, distribution, metabolism, and excretion of ENMs on a case-by-case basis, and investigate how interactions with the immune system affect the toxicokinetics of ENMs;
- Develop more advanced nanomaterial-relevant models to study immunotoxicity, including more advanced in vitro model systems to study the immunotoxicity of ENMs, taking into account the interplay between immune cell populations and other cells (for example, lung epithelial cells), as well as the role of the biocorona on the surface of ENMs;
- Unravel mechanisms of ENM immunotoxicity and develop adverse outcome pathways, and define patterns of responses applying to different groups of ENMs to facilitate risk assessment of ENMs;
- Develop an intelligent, mechanism-based, tiered testing strategy for ENMs taking into account the four fundamental steps of traditional risk assessment (hazard identification, hazard characterization, exposure assessment, and risk characterization);
- Identify susceptible populations at greatest risk for potential adverse effects of nanomaterials on immune-mediated disease (taking account of such criteria as sex, age, ethnicity, pre-existing condition);
- Develop approaches to immunotoxicology of complex mixtures of ENMs and other compounds;
- Establish acceptable uncertainty associated with exposure to nanomaterials; and
- Adapt Organization for Economic Cooperation and Development (OECD) test guidelines related to immune toxicity to include the assessment of nanomaterials.
On May 5, 2020, the European Union (EU) Observatory for Nanomaterials (EUON) published a Nanopinion entitled “NanoApp helps navigate legal obligations under REACH.” Olivier de Matos, Secretary General of the European Center for Ecotoxicology and Toxicology (ECETOC), describes the web-based app that was designed to help registrants follow the European Chemicals Agency’s (ECHA) guidance on sets of nanoforms. According to de Matos, the app primarily covers the “Appendix for nanoforms applicable to the Guidance on Registration and Substance Identification.” The NanoApp has two main tiers:
- Tier 1 asks users to provide basic data required for preparing their registrations in IUCLID about the nanoforms being assessed. Based on transparent similarity algorithms and decision rules, the app then establishes whether two or more of those nanoforms can be grouped into a single set based on the intrinsic similarity of their basic properties; and
- Tier 2 applies when criteria for Tier 1 grouping are not fulfilled, but the similarity values for the basic properties are still within predefined boundaries. The app then guides users on what data should be generated to support the justification of that potential set of nanoforms. This could be data on dissolution, dispersion stability, or in vitro When these data are introduced in the app, it gives the result of the final evaluation and concludes whether the set can be justified.
According to de Matos, the app has established criteria and rules that systematically evaluate the similarity between nanoforms, and on that basis, conclude whether a set of nanoforms can be justified. Initiated by ECETOC, the app was developed by a core team of BASF in Germany, Leitat in Spain, and ThinkWorks in the Netherlands. de Matos states that the decision logic, methods, and cut-offs used were all discussed with industry, including members of the ECETOC Nano Task Force and the academic and regulatory partners of the EU-funded Horizon 2020 research project GRACIOUS. ECETOC then gave a demo of the app to ECHA, and ECHA participated in testing the beta version and reviewing the rationales for the methods and the cut-offs it uses. ECETOC is cooperating with the Nanotechnology Industries Association (NIA) to involve its members further and describe the tool and its use. de Matos notes that the methods used to generate data that characterizes nanomaterials and their functionalities, as well as the cut-offs to decide on the similarity of nanoforms, will most likely be amended and refined in the future. The NanoApp is currently in beta testing and is available to anyone interested in testing the app. Once the final version of NanoApp is complete, ECETOC will provide training on how to use it.
On May 4, 2020, the U.S. Environmental Protection Agency (EPA) published proposed significant new use rules (SNUR) under the Toxic Substances Control Act (TSCA) for chemical substances that were the subject of premanufacture notices (PMN) and are subject to orders issued by EPA pursuant to TSCA. 85 Fed. Reg. 26419. The SNURs require persons who intend to manufacture (defined by statute to include import) or process any of these chemical substances for an activity that is proposed as a significant new use to notify EPA at least 90 days before commencing that activity. The substances subject to the proposed SNURs include carbon nanotubes (generic). According to EPA, the PMN states that the use of the PMN substance will be as a chemical intermediate to manufacture functionalized carbon nanotubes by oxidation with nitric acid; an additive in rubber polymers to improve mechanical/physical/chemical/electrical properties; an additive in resin polymers to improve mechanical/physical/chemical/electrical properties; an additive in metals to improve electrical/thermal properties; an additive in ceramics to improve mechanical/electrical/thermal properties; a semi-conductor, conductive, or resistive element in electronic circuitry and devices; an electric collector element or electrode in energy devices; a photoelectric or thermoelectric conversion element in energy devices; a catalyst support element or catalytic electrode for use in energy devices; an additive for transparency and conductivity in electronic devices; and an electro-mechanical element in actuator, sensor, or switching devices. Based on carbon nanotube analogues, data submitted for the PMN substance, and comparison to analogous respirable, poorly soluble particulates, EPA identified concerns for pulmonary toxicity and oncogenicity. EPA notes that it issued a direct final SNUR for this PMN substance on November 17, 2016, and withdrew it on January 19, 2017, in response to the PMN submitter’s intent to submit adverse comments, which was a request to modify the original TSCA Section 5(e) Order to add more uses. EPA states that it issued the Order (as modified) under TSCA Sections 5(a)(3)(B)(ii)(I) and 5(e)(1)(A)(ii)(I), based on a finding that in the absence of sufficient information to permit a reasoned evaluation the substance may present an unreasonable risk of injury to human health and the environment. To protect against these risks, the TSCA Order requires:
- Use of personal protective equipment where there is a potential for dermal exposure;
- Use of a National Institute for Occupational Safety and Health (NIOSH)-certified respirator with an Assigned Protection Factor (APF) of at least 50 where there is a potential for inhalation exposure;
- Use of the PMN substance other than as allowed in the TSCA Order;
- Waste streams from manufacture, processing, and use must be disposed of only by incineration or landfill; and
- No predictable or purposeful release of a manufacturing, processing, or use stream associated with any use of the PMN substance into the waters of the United States.
The proposed SNUR would designate as a “significant new use” in the absence of these protective measures. According to the notice, EPA has determined that certain information about the environmental effects of the PMN substance may be potentially useful in support of a request by the PMN submitter to modify the TSCA Order, or if a manufacturer or processor is considering submitting a significant new use notice (SNUN) for a significant new use that would be designated by this SNUR. The notice states that the results of chronic aquatic toxicity testing, with natural organic matter (NOM) as the dispersant, may be potentially useful to characterize the environmental effects of the PMN substance. Although the TSCA Order does not require these tests, EPA notes that the TSCA Order’s restrictions remain in effect until the TSCA Order is modified or revoked by EPA based on submission of this or other relevant information. Comments on the proposed SNURs are due June 3, 2020.
The International Organization for Standardization (ISO) has published standard ISO/TS 21412:2020, “Nanotechnologies — Nano-object-assembled layers for electrochemical bio-sensing applications — Specification of characteristics and measurement methods.” The standard specifies the characteristics to be measured of nano-object-assembled layers on electrodes by means of a solution process and of nano-objects constituting the layers for electrochemical applications such as nano-biosensor or diagnosis applications. It also provides measurement methods for determining the characteristics. ISO notes that the standard does not apply to:
- The requirements of nanostructures by top-down nanomanufacturing;
- The subsequent coating of materials such as biomaterials onto nano-object-assembled layers;
- Specific health and safety requirements during manufacturing;
- The experimental conditions of electrochemical sensing; and
- The packaging, labeling, expiration dates, and transport of nano-object-enhanced electrochemical electrodes.
The Nanotechnology Entrepreneurship Network (NEN) aired a special episode of its podcast on March 31, 2020, “Resources for Small Businesses Impacted by COVID-19: A Conversation with Jennifer Shieh.” The episode features a conversation between Dr. Lisa Friedersdorf, Director of the National Nanotechnology Coordination Office (NNCO), and Dr. Jennifer Shieh, Chief Scientist and Program Manager at the U.S. Small Business Administration (SBA). Dr. Shieh discusses the resources available to small businesses impacted by the COVID-19 pandemic.
As reported in our November 19, 2019, blog item, NEN brings new and seasoned entrepreneurs together with the people and resources available to support them. The NEN podcast highlights best practices, resources, and advice from entrepreneurs.
On April 7, 2020, the European Union (EU) Observatory for Nanomaterials (EUON) published a Nanopinion entitled “Carbon Nanotubes — First nanomaterial of high concern on the SIN List.” As reported in our November 27, 2019, blog item, ChemSec added carbon nanotubes to the Substitute It Now (SIN) List in November 2019. According to Dr. Anna Lennquist, Senior Toxicologist, International Chemical Secretariat (ChemSec), ever since ChemSec created the SIN List, there have been requests to add nanomaterials to the List. Lennquist states that several studies of different types of multi-walled carbon nanotubes show carcinogenicity for lungs, and the International Agency for Research on Cancer (IARC) classified one type as “possibly carcinogenic to humans” in summer 2019. Genotoxicity and lung damage have been shown by more types of carbon nanotubes, including single-walled, double-walled, and multi-walled. According to Lennquist, “[t]he persistence of carbon nanotubes under realistic conditions has been proven,” and, for single-walled carbon nanotubes, “there is evidence of reprotoxic effects.” Lennquist acknowledges that there were “many discussions internally, as well as with experts, before deciding to place all carbon nanotubes as one entry on the SIN List.” ChemSec chose a single entry for practical, political, and scientific reasons: consumer products often consist of several types of carbon nanotubes; ChemSec is “striving politically towards a more groupwise regulation of chemicals,” and “scientifically we could not justify where to draw a line between hazardous and less hazardous carbon nanotubes.” Lennquist states that with the addition of carbon nanotubes to the SIN List, “we want to show that nanoforms can and should be evaluated as any other chemical substance. Not all nanomaterials are safe, not all are hazardous, but it must be a case-by-case assessment.”