Nano and Other Emerging Chemical Technologies Blog

Nano and Other Emerging Chemical Technologies Blog

Regulatory & legal developments involving nano and other emerging chemical technologies

ISO Standard Describes Aerosol Generation for Air Exposure Studies of Nano-Objects and Their Aggregates and Agglomerates

Posted in International, Research

The International Organization for Standardization (ISO) recently published standard ISO/TR 19601:2017, “Nanotechnologies — Aerosol generation for air exposure studies of nano-objects and their aggregates and agglomerates (NOAA).”  ISO states that, to evaluate the inhalation toxicity of NOAA, it is important to consider certain parameters that make the toxicity testing relevant to human exposure.  Three critical aspects to consider when designing and conducting an inhalation toxicity study are:

  • Uniform and reproducible nano-object aerosol generation that is relevant to realistic exposures,
  • Thorough characterization of nanomaterials throughout the duration of testing including starting and generated materials; and
  • Use of occupational exposure limits and reference concentrations (as derived from existing studies and/or real-time exposure monitoring data) for dosimetry.

Therefore, according to ISO, to conduct in vitro and in vivo NOAA studies, “it is important to choose an appropriate NOAA aerosol generator and use online and off-line techniques for nano-object characterization.”  The standard describes methods for producing NOAA aerosols for in vivo and in vitro air exposure studies.  The purpose of the standard is to aid in selecting an appropriate aerosol generator to fulfill a proposed toxicology study design.  The standard describes characteristics of aerosol generation methods, including their advantages and limitations.  ISO notes that the standard does not provide guidance for aerosolization of specific nano-objects.

WHO Seeks Comment on Draft Document Concerning Assessing the Risk of Immunotoxicity Associated with Exposure to Nanomaterials

Posted in International, Legal/Regulatory Issues, Research

The World Health Organization’s (WHO) International Program on Chemical Safety (IPCS) published a draft Environmental Health Criteria (EHC) Document, Principles and Methods to Assess the Risk of Immunotoxicity Associated with Exposure to Nanomaterials.  According to IPCS, the target audience is risk assessors in a regulatory setting, researchers, and industry that needs to provide the data for assessment.  The draft EHC Document states that recent reports have identified engineered nanomaterials as potential stimulants of immune response that may culminate in eventual immunotoxicity.  The draft EHC Document acknowledges that there are no validated methodology available to assess the immunotoxicity of nanomaterials, and outlines several assays that are conventionally used to assess chemical-induced immunotoxicity that may be compliant with nanomaterial testing.  In general terms, according to the draft EHC Document, risk assessment of nanomaterials should follow the risk assessment paradigm for chemicals — hazard identification, hazard characterization, exposure assessment, and risk characterization.  The draft EHC Document states that the design to perform risk analysis should be done on a case-by-case basis, flexibly including the components most appropriate for the material and its proposed use.  The draft EHC Document includes case studies for carbon nanotubes and silver nanoparticles.  Comments are due July 21, 2017.

EC Publishes Catalog of Nanomaterials Used in Cosmetic Products Placed on the EU Market

Posted in EU Member State, Legal/Regulatory Issues

On June 15, 2017, the European Commission (EC) published a catalog of nanomaterials used in cosmetic products on the European Union (EU) marketRegulation (EC) No. 1223/2009 on cosmetic products requires the EC to publish a catalog of all nanomaterials used in cosmetics placed on the market, indicating the categories of products and the reasonably foreseeable exposure conditions.  Under the Regulation, the catalog was due by January 11, 2014.  As reported in our February 13, 2017, blog item, the EC postponed publication of the catalog several times due to the allegedly poor quality of the information it received from industry.  The EC based the catalog on information notified electronically to the EC through the Cosmetic Products Notification Portal (CPNP).  The EC states that it “takes no responsibility for the content and the scientific qualification of the notifications made in the CPNP.”  The functions of the nanomaterials listed in the catalog (12 as colorants, six as ultraviolet (UV)-filters, and 25 as other functions) are based on the names of substances notified and, generally, on the corresponding functions that are displayed in the CosIng database and where relevant on other information at the disposal of the EC.  Some substances may have more than one function.  The EC notes that the catalog “has an informative value only and is not in any case a list of authorised nanomaterials.”  The EC is required to update the catalog regularly and make it publicly available.

ECHA Launches EU Observatory for Nanomaterials

Posted in International, Legal/Regulatory Issues, Occupational Health and Safety Issues, Research

On June 14, 2017, the European Chemicals Agency (ECHA) announced the launch of the European Union (EU) Observatory for Nanomaterials (EUON).  ECHA states that EUON “offers a unique web-based information point with factual and neutral content about nanomaterials on the EU market.”  EUON is targeted at a wide audience, including consumers, workers, regulators, and scientists.  EUON provides information on uses, health and safety issues, research, regulation, and international activities.  According to ECHA, EUON will be further developed in the coming years with new content to meet the audiences’ needs.  EUON will also carry out studies and make use of external databases and publications.  ECHA is hosting EUON based on a formal delegation agreement between ECHA and the European Commission (EC).  The agreement, signed at the end of 2016, runs until 2020.  ECHA notes that the EC concluded that EUON “is the most efficient and proportionate measure to increase transparency and availability of information regarding nanomaterials.”

Sweden to Require Information on Nanomaterials in Product Register Notifications

Posted in EU Member State, International, Legal/Regulatory Issues

On June 7, 2017, Sweden notified the European Commission (EC) that it intends to amend the information requirements concerning the Swedish Chemicals Agency’s (KEMI) product register to require notifiers to provide information on nanomaterials contained in the product.  Under the draft regulation, the requirement will apply to nanomaterials that have been intentionally added to the product, regardless of the concentration of the nanomaterials.  The definition of nanomaterial will reflect the EC’s recommended definition, except that nanomaterials that are natural or incidental shall not be notified to the product register.  Exemption from the notification obligation is proposed for nanopigments and for entities with an annual turnover of less than SEK 5 million.  Those covered by the exemption will provide information only as to whether a component is a nanomaterial.  Other information may be provided on a voluntary basis.  These exceptions will be valid for an evaluation period of three years.  Product groups that are already exempt from the required registration in the product register will remain exempt, including waste, foodstuffs and animal feed, medicinal products, cosmetics, and tattoo inks.  KEMI intends the rules on notification of nanomaterials to the product register to enter into force on January 1, 2018.  Information on the presence of nanomaterials will be reported to KEMI’s product register beginning in February 2019.

ECHA Committee Concludes Titanium Dioxide Should Be Classified as Suspected of Causing Cancer When Inhaled

Posted in International, Legal/Regulatory Issues

On June 9, 2017, the European Chemicals Agency (ECHA) announced that the Committee for Risk Assessment (RAC) “concluded that the available scientific evidence meets the criteria in the [Classification, Labeling and Packaging (CLP)] Regulation to classify titanium dioxide as a substance suspected of causing cancer through the inhalation route.”  In May 2016, France submitted a proposal for harmonized classification and labeling (CLH).  The proposal’s conclusions on classification and labeling state:

TiO2 should be considered as being potentially carcinogenic to humans when inhaled and thus be classified Carc. Cat 1B-H350i.  This classification applied for both fine particles and nanomaterials of TiO2 without being able of any distinction in terms of morphology, crystal phase, and surface treatment.

RAC assessed the carcinogenic potential of titanium dioxide against the CLP criteria and, having considered the available scientific data, concluded that it meets the criteria to be classified as suspected of causing cancer (category 2, through the inhalation route).  According to ECHA, RAC concluded that there was insufficient evidence to classify titanium dioxide in the more severe category for carcinogenicity (category 1B) as was originally proposed by France.  This more severe category refers to a substance that is presumed to cause cancer.  Following adoption, RAC’s opinion will go through a normal editorial check before it is sent to the European Commission for final decision making.  The opinion will be made available on ECHA’s website at that time.

Australian Consultation Paper Addresses Regulatory Treatment of Unlisted Chemicals Introduced at the Nanoscale

Posted in International, Legal/Regulatory Issues

The Industrial Chemicals Bill 2017 describes the legislative framework for a reformed, risk-based regulatory scheme for Australia to continue to regulate the introduction of industrial chemicals.  The Australian government has presented the bill to Parliament.  On June 1, 2017, the National Industrial Chemicals Notification and Assessment Scheme (NICNAS) published Consultation Paper 5, which seeks feedback from stakeholders on the detail to be included in delegated legislation made under the framework established by the Industrial Chemicals Bill.  The Consultation Paper states that these are mostly “technical matters” and “relate in particular to the categorisation and assessment of unlisted chemical introductions.”  Part 7 of the Consultation Paper is a proposal for the categorization of industrial chemicals introduced at the nanoscale.  It presents options for the properties of nanoscale chemicals that should be used as criteria to define the chemicals that require pre-introduction assessment.  NICNAS states that it modified its proposal to address stakeholder feedback and concerns, and Consultation Paper 5 further refines the regulatory treatment of chemicals introduced at the nanoscale.  NICNAS proposes that it will not categorize introductions of unlisted chemicals consisting of particles at the nanoscale using the same hazard and exposure band criteria proposed for other chemicals.  Instead, NICNAS will set criteria using properties important for establishing which nanoscale chemicals require pre-introduction assessment.  The categorization outcomes for unlisted chemicals consisting of particles at the nanoscale that meet the specific nanoscale criteria will be:

  • Exempted if introduced at ≤10 kilograms per year (kg/annum) for the purposes of research and development, or as a contained import/export introduction;
  • Reported if introduced at >10 kg/annum and ≤100 kg/annum for the purposes of research and development; and
  • Assessed in all other circumstances.

NICNAS states that the information it will need as part of the application for an Assessed introduction will be commensurate with the Exposure Band (similar to other types of industrial chemicals).  NICNAS will consult further on these requirements later in 2017.  Categorization criteria may incorporate some or all of the below elements, and the Consultation Paper seeks comment on specific options within each element:

  • Size and distribution;
  • Intentionally manufactured;
  • Size-dependent properties;
  • Aggregates and agglomerates; and
  • Solubility/dissolution rate.

For the introduction of chemicals consisting of particles at the nanoscale that do not meet the criteria discussed in Consultation Paper 5, the categorization will be the same as other unlisted industrial chemicals and may result in it being categorized as Assessed, Reported, or Exempted.  It will therefore depend on the exposure (volume and use) and the hazard characteristics of the chemical (with information requirements for hazard depending on the Exposure Band).  NICNAS will hold the following public workshops:

  • Sydney public workshop, June 16, 2017, 9:30 a.m. to midday; and
  • Melbourne public workshop, June 28, 2017, 9:30 a.m. to midday.

Comments on Consultation Paper 5 are due July 12, 2017.

ISO Publishes Standard Providing Plain Language Explanation of Selected Terms from ISO/IEC 80004 Series

Posted in International, Legal/Regulatory Issues

The International Organization for Standardization (ISO) published standard ISO/TR 18401:2017, “Nanotechnologies — Plain language explanation of selected terms from the ISO/IEC 80004 series.”  The standard is intended to assist stakeholders who are making decisions about the direction, management, and application of nanotechnologies to understand better selected key terms and definitions in the ISO/IEC 80004 vocabulary series for nanotechnologies.  The standard offers explanations, including examples, of selected nanotechnology terms and is intended to facilitate an understanding of the use and applications of nanotechnology.  The specific aim is to:

  • Promote consistent usage and reduce misinterpretation of terms among users; and
  • Facilitate communication and understanding in developing or commercializing applications of nanotechnologies.

The standard contains selected key terms and provides definitions and explanations intended to aid understanding and illustrate, where applicable, the relationship between one term and another, using practical examples where possible.  Explanations and examples are chosen to underpin the selected terms published in the ISO/IEC 80004 vocabulary series.

KAN Reviews Nanotechnology Standardization Documents from OSH Perspective

Posted in International, Legal/Regulatory Issues, Occupational Health and Safety Issues

Germany’s Commission for Occupational Health and Safety (KAN) released in May 2017 a report entitled Standardization in nanotechnology — Status review and requirements analysis from the occupational safety and health perspective.  According to the report, which is in German but includes an English summary, the authors conducted a structured status review of the standardization situation in the field of nanotechnology.  Approximately 260 standardization documents related to nanotechnology were identified, including published standards, draft standards, technical specifications, and reports, as well as (proposed) work items.  The majority of the documents describe testing and measurement methods.  Others are concerned with terminology, material specifications, process descriptions, and guidance.  The evaluation of the findings focuses on a comparison with national and European rules and regulations and identifies loopholes.  The results are then used as the basis for recommendations to help occupational safety and health (OSH) experts exert a targeted influence on standardization in nanotechnology and prevent standards that conflict with established rules and regulations.  KAN’s recommendations include requesting that the Federal Ministry of Labor and Social Affairs/the Federal Institute for Occupational Safety and Health urge the European Commission to:

  • Make clear the cross-references and differences between the European Union definition of nanomaterials and internationally harmonized definitions;
  • Address “advanced materials,” in addition to nanomaterials, in the subject matter dealt with in legislation and, while doing so, make reference to European/international harmonized OSH-relevant definitions in standards;
  • Promote the development of methods that cover the difficult measuring requirements in risk assessments of nanomaterials used in workplace practice;
  • Take into account the findings of safety research on nanomaterials that show that other innovative materials can also lead to similar hazards for workers;
  • Supplement the testing requirements for nanomaterials and other “advanced materials” with similar health hazards in the Registration, Evaluation, Authorization and Restriction of Chemicals (REACH) regulation annexes and in guidelines;
  • Add these properties to the data required on the safety data sheet so that they are communicated to the supply chain; and
  • Introduce methods with which to group nanomaterials by their hazardous properties.

ISO Publishes Procedure for Detecting Reactive Oxygen Species Generated by Metal Oxide Nanomaterials

Posted in International, Research

The International Organization for Standardization (ISO) recently announced publication of standard ISO/TS 18827:2017, “Nanotechnologies — Electron spin resonance (ESR) as a method for measuring reactive oxygen species (ROS) generated by metal oxide nanomaterials.”  The introduction states that the use of metal or metal oxide-based nanomaterials has dramatically increased in biomedical and industrial applications.  The scientific basis for the cytotoxicity and genotoxicity of most manufactured nanomaterials are not fully understood, however.  The study of the hazardous effects of metal oxide nanomaterials is still in its initial stages.  The ability to generate ROS is one main source of toxicity of metal oxide nanomaterials.  According to the introduction, overproduction of ROS can induce oxidative stress, resulting in cells failing to maintain normal physiological redox-regulated functions.  This in turn may lead to DNA damage, unregulated cell signaling, change in cell motility, cytotoxicity, apoptosis, and cancer initiation. Critical determinants that can affect the generation of ROS include size, shape, particle surface, surface positive charges, surface-containing groups, particle dissolution, metal ion release from nanometals and nanometal oxides, ultraviolet (UV) light activation, aggregation, mode of interaction with cells, inflammation, and pH of the medium.  Thus, to detect and quantify ROS formation on the surface of metal oxide nanomaterials, the standard suggests the ESR method.  The standard specifies methods of detection by ESR of 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) hydroxyl adduct, 5-tert-butoxycarbonyl-5-methyl-1-pyrroline-N-oxide (BMPO) superoxide adduct, and 2,2,5,5-tetramethyl-3-pyrroline-3-carboxamide (TPC) singlet oxygen adduct formation from metal oxide nanomaterials.  The standard provides a method to assess ROS generation on the metal oxide nanomaterials in a cell free condition.  According to ISO, this method may provide valuable information for the prediction of ROS-mediated cytotoxicity without cytotoxicity assay at physico-chemical evaluation phase.