International regulatory and methodological framework for ensuring security in field of nanoindustry
he development of the nanoindustry initiates two activities related to the notion of security as "a state of protection of the vital interests of the individual, society and the state against internal and external threats" :
• analysis of the causes of nano-threat;
• use of nanomaterials and nanotechnologies to create safety systems .
Nanoparticles and nanomaterials often have properties that are radically different from the properties of the same substance in the form of macroscopic dispersions or continuous phases , and therefore create a fundamentally new impact factor on the organism and its habitat. This necessitates the development of methods for assessing the risk of negative effects of nanomaterials on human health and the organization of control over their turnover .
Metrology and standardization of nanotechnologies are becoming increasingly important in the era of globalization. The use of nanotechnology has greatly accelerated in many countries, which was caused by the implementation of the National Nanotechnology Initiative, published in the USA in 2000 , and a number of similar programs. In various industries, nanotechnology is the driving force for improving existing and creating new products. The progress in the development of such products determines the need for the development and use of advanced research methods. In addition, the commercialization of nano-products in the global market requires international standardization, which lays the foundation for the spread of nanotechnology in society. In this regard, the importance of international standards and standardization activities is constantly increasing .
The purpose of this article is to analyze the current state of regulatory and methodological support for the safety of processes and products of the nanoindustry abroad to select the relevant areas of domestic and international efforts in this field. This publication should be considered as a development of the ideas presented by the authors in .
For convenience of naming international and foreign national organizations, English-language abbreviations are used, presented in Table 1.
ACTIVITIES OF INTERNATIONAL ORGANIZATIONS ON STANDARDIZATION OF SECURITY IN FIELD OF NANOTECHNOLOGY
In the early 2000's (even before the adoption of international standards in the field of nanotechnology), several national and regional standards were adopted. China became the first country to develop National standards in nanotechnology in December 2003. In 2004, the BSI Committee for Nanotechnologies (NTI/1) (UK), the Nanotechnology Standards Panel in ANSI and the Nanotechnology Standardization Committee (Japan) were formed.
In the years 2005–2006 a number of large standards organizations (ISO, ASTM, CEN, IEC) have established specialized technical committees that have developed a set of standards related to terminology, physical, chemical and biological measurements, as well as environmental protection and safety of nanomaterials and nanotechnologies [6, 7].
At present, national and regional organizations are increasingly focusing on ensuring a coordinated contribution to the international efforts of ISO, ASTM and OECD, and not on the development of independent national standards .
ISO is a non-governmental organization with a network of national standards institutions in 162 countries. The role of ISO is to promote the internationalization and harmonization of standards and related activities. As voluntary consensus standards, ISO documents do not establish rules, but can support public policy and be included in national and regional regulation of standardization issues .
ISO standards and other documents are developed in the framework of technical committees, which include experts representing industry, non-governmental organizations, governments and other stakeholders that are nominated by ISO members.
In 2005, the Technical Committee 229 Nanotechnologies (ISO/TC 229) was established in ISO, whose secretariat function is performed by BSI. Its active members include 35 countries (including Russia), and 16 countries are observers . The primary objectives of ISO/TC 229 are to standardize the following areas :
• terms and definitions;
• metrology and methods of testing and measurement;
• standard samples of composition and properties;
• process modeling;
• medicine and safety;
• environmental impact.
Within the technical committee ISO/TC 229 there are four working groups:
• Terminology and nomenclature (WG1). Scope of activities includes standardization of terminology and nomenclature in the field of nanotechnology to facilitate communication and promote common understanding.
• Measurement and characterization (WG2). Scope of activities includes standardization of measurements, characteristics and methods of testing of nano-products, taking into account the requirements for metrology and standard samples.
• Health, safety and environmental aspects of nanotechnologies (WG3). Scope of activities includes standardization in the field of health, safety and environmental aspects of nanotechnology.
• Material specifications (WG4). Scope of activity includes standardization of compositions, properties and characteristics of manufactured nanomaterials .
In 2008, ISO/TC 229 issued a technical report ISO/TR 12885:2008, describing the impact of nanotechnology on health and safety, which summarizes world experience and makes it available as long as the national standards of many countries on nanotechnology are still under development. This report contains advice to researchers and manufacturers on ensuring the safety of personnel and consumers in the production, storage, use and utilization of industrial nanomaterials .
In 2009, ISO/TC 229 developed a plan for the standardization of nanotechnologies, aimed, among other things, to support the promotion of quality and safety, the protection of the acquirer and the environment, and the rational use of resources in nanotechnology applications .
The document system developed by the WG3 consists of several functional blocks covering the following aspects of control of nanotechnologies and nanomaterials:
• inhalation and exposure to nanoparticles (Table 2);
• health and safety protection in the field of nanotechnology (Table 3);
• management of professional risks in the nanoindustry (Table 4);
• methods for detecting and measuring the toxicity of specific nanomaterials (Table 5).
In the field of inhalation exposure to nanoparticles, standards related to the production of nano-aerosols (ISO 10801:2010)  and their characterization for tests for inhalation toxicity (ISO 10808:2010) have been developed . Technical Report ISO/TR 19601:2017 describes methods for obtaining nano-aerosols for studies of the effects of air in vivo and in vitro .
Technical Committee ISO/TC 146 (Air Quality) developed the technical regulation ISO/TR 27628:2007, containing recommendations for characterizing the effect of nano-aerosols in the working environment .
In addition to the above-mentioned technical report ISO/TR 12885:2008, several other documents have been issued that regulate health and safety practices in the field of nanotechnology. They concern the development of safety data sheets for substances containing nanomaterials (ISO/TR 13329:2012) , the determination of occupational exposure limits and bands for nano-objects and their aggregates and agglomerates (ISO/TR 16837:2016)  and the physical-chemical characterization of engineered nanoscale materials for toxicological assessment (ISO/TR 13014:2012) . There are also papers on in vitro and in vivo methods for toxicological and eco-toxicological screening of engineered and industrial nanomaterials (ISO/TR 16197:2014) , and cell-free in vitro test systems and techniques for assessing the biodurability of nanomaterials (ISO/TR 19057:2017) .
To manage risks in the nanoindustry, WG3 developed three documents.
Technical Report ISO/TR 13121:2011 describes the process of identifying, evaluating, reviewing, deciding and informing about potential risks in the development and use of manufactured nanomaterials in order to protect the health of consumers and workers and ensure environmental safety .
The technical specification ISO/TS 12901:2012 contains guidelines for occupational safety and health in the field of nanomaterials, including the use of technical means of control and appropriate personal protective equipment, for spill and emergency emissions response, and the proper handling of such materials during disposal .
The technical specification ISO/TS 12901-2:2014 describes the use of the control banding approach to control the risks associated with exposure to nanoparticles, even if data on their toxicity and quantitative impact assessments are limited or absent .
The latest group of standards developed by the WG3 regulates methods for detecting and measuring the toxicity of specific nanomaterials. It includes two documents that are devoted to the measuring reactive oxygen species generated by nanomaterials in aqueous solutions using the electron spin resonance method (ISO/TS 18827:2017)  and their determination in vitro in cells exposed to nano-objects using oxidative stress indicators (ISO/TS 19006:2016) .
In addition, three papers have been developed on the toxicity of suspensions of nano-objects. Technical specification ISO/TS 19337:2016 describes the characteristics of working suspensions of nano-objects for in vitro studies of their toxicity . ISO 29701:2010 standardizes the test using LAL reagent (limulus amebocyte lysate), intended for the toxicological evaluation of nanomaterial suspensions in vitro . Technical specification ISO/TS 20787:2017 regulates the assessment of the water toxicity of manufactured nanomaterials in saltwater .
The world's leading organization for the development and publication of international standards for electrical, electronic and related technologies is IEC . In May 2006, IEC established Technical Committee 113: Nanotechnology for electrotechnical products and systems (IEC/TC 113) . This structure deals with the standardization of solutions related to electrical and electronic products and systems in the field of nanotechnology, in close cooperation with other IEC committees and ISO/TC 229 . The activities of IEC/TC 113 cover, in particular, the evaluation of the productivity, reliability and safety of nanomaterials throughout the life cycle of the final product.
The DIN acts as the secretariat of IEC/TC 113. The IEC/TC 113 consists of two working groups united with the TC ISO 229: Terminology and nomenclature (JWG1) and Measurement and characterization (JWG2), as well as six independent working groups. It consists of 16 active member countries (including Russia) and 18 observer countries that are members of the IEC.
The Joint Working Group JWG2 is developing standards for measuring and characterizing nanomaterials, which are very important, as the definition of physical and chemical properties is crucial to understanding the impacts and hazards of nanomaterials. In total, the joint working group JWG2 published or is developing 31 standards .
In Russia, the functions of the permanent national working body of ISO/TC 229 and IEC/TC are assigned to TC 441 Nanotechnology of Federal Agency on Technical Regulating and Metrology .
Within the framework of the Organisation of the Environment, Health and Safety Programme (OECD), products of the chemical and biotechnological industry are considered that affect the environment, the economy, health and living standards. A special section of this program is devoted to the safety of industrial nanomaterials. In order to ensure compliance with security requirements, OECD members joined their efforts in the implementation of the programme. The following main tasks are being solved:
• active exchange of information on security issues;
• verification of the adequacy of the methodology for risk assessment and testing schemes for nanomaterials;
• international coordination on regulatory issues .
As part of the OECD, a working group on manufactured nanomaterials and a working group on nanotechnologies have been created, and they have produced more than 90 reports on the safety of manufactured nanomaterials [32, 33].
The IRGC is also concerned with regulation of nanotechnology safety , which in particular developed the Guidance on risk assessment concerning potential risks arising from applications of nanoscience and nanotechnologies to food and feed  and the IRGC guidelines for emerging risk governance .
US REGULATORY AND METHODOLOGICAL FRAMEWORK IN FIELD OF NANOTECHNOLOGY SAFETY
In the US, three organizations are involved in the standardization of nanotechnology: ASTM, ANSI and IEEE .
In 2005, the ASTM formed Committee E56 on nanotechnology. Its activities are related to standards and guidelines in the field of nanotechnology and nanomaterials, as well as the coordination of ASTM's ongoing standardization work in accordance with the needs of the nanoindustry . The E56 includes two subcommittees that develop standards in the field of nanotechnology safety:
• Е56.02 – Physical and Chemical Characterization;
• Е56.03 – Environment, Health, and Safety .
The E56 focuses on standardizing the measurement of nanoparticle properties using various methods (Table 6). Subcommittee E56.02 developed seven standards regulating the physical-chemical characterization and determination of nanoparticle size, their size distribution, surface area and zeta potential. The four main physical-chemical indicators listed above determine biological properties, including toxicity [38–44]. Subcommittee E56.03 has developed four standards regulating the determination of biological properties and the processing of nanoparticles under industrial conditions [45–48].
In 2004, ANSI formed a Nanotechnology Standards Panel to coordinate the development of standards for nanotechnology applications .
Studies of the ecological safety of products created using nanomaterials are conducted in the USA by the EPA . First of all, this concerns products containing silver nanoparticles with antimicrobial effect . In addition, the EPA has developed the "Nanotechnology White Paper" .
The FDA controls the safety, efficacy and reliability of drugs, medical devices, biotechnological products, textiles, vaccines, cosmetics and pharmaceuticals created using nanotechnology for humans and animals . In 2006, the FDA's Nanotechnology Task Force was established to assess the safety of products containing nanomaterials .
NORMATIVE AND METHODOLOGICAL BASE OF EU
ON ENSURING SECURITY IN FIELD OF NANOTECHNOLOGY
In Europe, standards are developed and agreed by the three standardization organizations: CEN, CENELEC and ETSI .
CEN brings together national standardization agencies in 33 countries. In 2005, the Technical Committee 352 on Nanotechnology (CEN/TC 352) was established. CEN/TC 352 and ISO/TC 229 have similar activities, structures and business plans. The functions of the secretariats of both committees are performed by BSI. CEN/TC 352 is preparing standards in the following areas:
• classification, terminology and nomenclature;
• metrology, measurement and characterization (including calibration);
• health, safety, environmental issues, nanotechnology products and processes.
The CEN/TC 352 consists of three working groups:
• Measurement, characterization and performance evaluation (WG1).
• Commercial and other stakeholder aspects (WG2).
• Health, safety and environmental aspects (WG3).
CEN/TC 352 maintains links with 22 European technical organizations and cooperates with 23 other CEN and ISO technical committees . CEN/TC 352 aims to develop common standards applicable to the widest possible range of industries in Europe and actively participates in the work of ISO/TC 229. The standards approved by CEN comply with ISO standards. In the field of safety of the nanoindustry, ISO/TC 229 has so far issued three standards that fully comply with ISO 10801:2010, ISO 10808:2010 and ISO 29701:2010.
In the years 2005–2006, 33 European countries established national nanotechnology committees within their national standardization bodies, 32 of which formally appointed their representatives to CEN/TC 352.
Countries that are members of the European Union and other international communities use national legislation based on or completely replicate ISO standards [5, 7]. For example, in the structure of BSI in 2004, a Committee for Nanotechnologies (NTI/1) was established . To date, BSI (along with participation in the development and application of ISO standards) has developed a number of national documents in the field of nanotechnology safety, including the terminology standard and three guiding regulatory documents (Table 7).
In addition, ECHA , EFSA  and other organizations are involved in regulation of nanotechnology safety in the European Union.
The regulatory regime for nanotechnological chemicals in the EU is defined in the Regulation on Registration, Evaluation and Authorisation of Chemicals (REACH). According to this document, all chemicals imported or produced in the EU are subject to regulatory oversight, and all companies are required to report about such substances, including recommendations for safe handling for risk management and information on their environmental, sanitary and toxicological properties .
A range of issues related to the possible risks of using nanotechnologies in food and feed production chains is discussed in the EFSA's "Guidance on risk assessment concerning potential risks arising from applications of nanoscience and nanotechnologies to food and feed" .
NORMATIVE-METHODICAL BASE OF PRC IN FIELD OF ENSURING SAFETY OF NANOTECHNOLOGIES
Nanotechnology standards in the People's Republic of China are adopted by the Nanotechnology Standardization Technical Committee (NSTC) and the National Technical Committee on Nanotechnology of Standardization Administration of China (SAC/TC 279).
NSTC develops test reports and technical standards used by manufacturing companies, and also supervises applied research in the field of industry and metrology and in particular supervises laboratory measuring instruments.
The SAC/TC 279 acts as the coordinating body for the development of basic standards in the field of nanotechnology, including terminology, methodology and safety of nanoscale measurements, materials and nano-biomedicine. SAC/TC 279 also creates a database for toxicology studies of nanomaterials to help define safety standards for their production, packaging and transport .
The development of the nanoindustry is characterized by high dynamics, multidisciplinary research and intersectoral engineering activities, which determines the need for the formation and use of regulatory and methodological safety in the development, production and use of nano-products.
Accelerated commercialization of nano-products, global trade and international cooperation in research and production processes require harmonization of interactions at the state level with the aim of analyzing and preventing nano-threats. This activity is one of the most popular modern areas of ensuring the security of the individual, state and society.
In the era of globalization and the accelerated evolution of interdisciplinary convergent technologies, the educational component of prevention of nano-threats in the framework of traditional disciplines in the areas of ecology and life safety is of particular importance [2, 3]. ■* Санкт-Петербургский государственный электротехнический университет "ЛЭТИ" (Санкт-Петербург, Россия) / Saint-Petersburg Electrotechnical University "LETI" (Saint-Petersburg, Russia).