ISO/TR 18637:2016
(Main)Nanotechnologies — Overview of available frameworks for the development of occupational exposure limits and bands for nano-objects and their aggregates and agglomerates (NOAAs)
Nanotechnologies — Overview of available frameworks for the development of occupational exposure limits and bands for nano-objects and their aggregates and agglomerates (NOAAs)
ISO/TR 16837:2016 provides an overview of available methods and procedures for the development of occupational exposure limits (OELs) and occupational exposure bands (OEBs) for manufactured nano-objects and their aggregates and agglomerates (NOAAs) for use in occupational health risk management decision-making.
Nanotechnologies — Vue d'ensemble des cadres disponibles pour la définition de limites et bandes d'exposition professionnelle applicables aux nano-objets, à leurs agrégats et agglomérats (NOAA)
L'ISO/TR 18637 :2016 fournit une présentation générale des méthodes et modes opératoires disponibles pour la définition de valeurs limites d'exposition professionnelle (VLEP) et de bandes d'exposition professionnelle (BEP) pour les nano-objets manufacturés et leurs agrégats et agglomérats (NOAA), destinés à être utilisés dans la prise de décision en matière de gestion du risque pour la santé au travail.
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Standards Content (Sample)
TECHNICAL ISO/TR
REPORT 18637
First edition
2016-12-01
Nanotechnologies — Overview
of available frameworks for the
development of occupational
exposure limits and bands for nano-
objects and their aggregates and
agglomerates (NOAAs)
Nanotechnologies — Vue d’ensemble des cadres disponibles pour la
définition de limites et bandes d’exposition professionnelle applicables
aux nano-objets, à leurs agrégats et agglomérats (NOAA)
Reference number
ISO/TR 18637:2016(E)
©
ISO 2016
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ISO/TR 18637:2016(E)
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ii © ISO 2016 – All rights reserved
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ISO/TR 18637:2016(E)
Contents Page
Foreword .iv
Introduction .v
1 Scope . 1
2 Normative references . 1
3 Terms and definitions . 1
4 Symbols and abbreviated terms . 3
5 Description of available processes for setting OELs and OEBs . 5
5.1 General considerations . 5
5.2 Description of evidence-based process . 6
5.3 Substance-specific OELs . 8
5.4 Categorical OELs . 8
5.5 Initial or default occupational exposure bands . 9
6 Substance-specific OELs for nanomaterials .10
6.1 General overview .10
6.2 Available substance-specific OELs .10
6.2.1 Carbon nanotubes .10
6.2.2 Nanoscale TiO .
2 11
6.2.3 Fullerenes . .12
6.3 Evaluation of OEL methods .12
6.3.1 Similarities and differences .12
6.3.2 Influence of methods on derived OEL values for nanomaterials .13
6.3.3 State of the science in support of risk assessment methods for
nanomaterials OELs .14
7 Categorical OELs for nanomaterials .15
7.1 Summary of options proposed .15
7.1.1 United Kingdom .15
7.1.2 Germany .15
7.1.3 NIOSH .17
7.1.4 Japan’s (AIST’s) approaches .17
7.1.5 OECD . .18
7.2 Evaluation of categorical OEL .19
7.2.1 Similarities and differences .19
7.2.2 State of the science supporting categorical OELs .20
8 OEBs and control banding for nanomaterials .21
8.1 Overview of current hazard and control banding schemes .21
8.1.1 Comparison of hazard bands and OEBs as applied to inhaled NOAAs .22
8.1.2 ISO hazard banding scheme for NOAAs .25
8.2 Case studies on banding NOAAs .26
8.3 Evaluation of the evidence for initial (default) OEBs for categories of NOAAs .28
8.3.1 Categorical analyses and read-across .28
8.3.2 Utility of in vitro data in OEL/OEB development for NOAAs . .29
8.3.3 Options for deriving an OEL or OEB for NOAAs .30
9 Feasibility considerations in the OEL and OEB setting process .30
Annex A (informative) Standard processes for OEL setting .32
Bibliography .62
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ISO/TR 18637:2016(E)
Foreword
ISO (the International Organization for Standardization) is a worldwide federation of national standards
bodies (ISO member bodies). The work of preparing International Standards is normally carried out
through ISO technical committees. Each member body interested in a subject for which a technical
committee has been established has the right to be represented on that committee. International
organizations, governmental and non-governmental, in liaison with ISO, also take part in the work.
ISO collaborates closely with the International Electrotechnical Commission (IEC) on all matters of
electrotechnical standardization.
The procedures used to develop this document and those intended for its further maintenance are
described in the ISO/IEC Directives, Part 1. In particular, the different approval criteria needed for the
different types of ISO documents should be noted. This document was drafted in accordance with the
editorial rules of the ISO/IEC Directives, Part 2 (see www.iso.org/directives).
Attention is drawn to the possibility that some of the elements of this document may be the subject of
patent rights. ISO shall not be held responsible for identifying any or all such patent rights. Details of
any patent rights identified during the development of the document will be in the Introduction and/or
on the ISO list of patent declarations received (see www.iso.org/patents).
Any trade name used in this document is information given for the convenience of users and does not
constitute an endorsement.
For an explanation on the meaning of ISO specific terms and expressions related to conformity assessment,
as well as information about ISO’s adherence to the World Trade Organization (WTO) principles in the
Technical Barriers to Trade (TBT) see the following URL: www.iso.org/iso/foreword.html.
The committee responsible for this document is ISO/TC 229, Nanotechnologies.
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ISO/TR 18637:2016(E)
Introduction
Nano-objects and their aggregates and agglomerates (NOAAs) represent a subset of particulate materials
that can be dispersed in the air and can represent health risks via inhalation exposures. NOAAs include
structures with one, two or three external dimensions in the nanoscale from approximately 1 nm to
100 nm, which may be spheres, fibres, tubes and others as primary structures. NOAAs can consist of
individual primary structures in the nanoscale and aggregated or agglomerated structures, including
those with sizes larger than 100 nm. An aggregate comprises strongly bonded or fused particles
[1][2][3][4]
(structures). An agglomerate is a collection of weakly bound particles (structures) .
The purpose of this document is to describe a general framework for the development of occupational
exposure limits (OELs) or occupational exposure bands (OEBs) for individual NOAAs or categories of
NOAAs with different levels of available data. OELs and OEBs are important tools in the prevention
of occupational illness. OELs have a long history in industrial hygiene and are based on observations
of workers or studies of laboratory animals. OELs are established to minimize the likelihood of
[5][6]
adverse effects from exposure to potentially hazardous substances in the workplace . An OEL is
generally substance-specific (although sometimes generically expressed, such as dust). Sufficient data
to develop an OEL may not be available, especially for substances such as NOAAs used in emerging
technologies. To aid in hazard communication and exposure control decisions for substances without
[7][8][9]
OELs, hazard banding has been used for many years . Substances are assigned to a hazard band
based on limited toxicity data usually from animal studies. Hazard banding schemes typically consist of
qualitative bands ranging from low to high severity of effects. Thus, a hazard band represents a range of
potential toxicities for a particular substance or category of substances. Some hazard banding schemes
[10]
include associated OEBs . The term OEB is a general term for exposure concentration ranges used
in some hazard banding schemes that are related to the ranges of hazard potentials. In contrast to an
OEB, an exposure band is a range of potential concentrations of a substance (or category of substances)
to which workers may be exposed in a defined occupational scenario and which is based on factors
such as the amount of NOAA processed or used, the nature of the process, and the form of the NOAA
[3]
including dustiness . In control banding, the hazard band and the exposure band are combined to
determine the control band for any particular occupational scenario (e.g. ISO/TS 12901-2).
OELs and OEBs are part of an overall occupational safety and health (OSH) program and are not
intended to identify and address all safety and health risks associated with a specific process or task.
OELs and OEBs are intended to provide occupational safety and health professionals with a health
basis for assessing the effectiveness of exposure controls and other risk management practices. The
exposure assessment of nanomaterials including carbon nanomaterials [such as fullerene, graphene,
single-walled carbon nanotube (SWCNTs) and multi-walled carbon nanotube (MWCNTs)], metal oxides
(TiO , SiO , zinc oxide, iron oxide), and metals (silver and gold nanoparticles) remains a challenge in
2 2
the field of occupational hygiene, as there have been relatively few studies on the characterization of
workplace exposures to NOAA. Sampling and analytical methods that have the capabilities to accurately
measure nanomaterials are still under development. Most sampling devices that measure airborne
particle count concentrations, such as condensation particle counters and optical particle counters,
cannot differentiate ambient exposures to background nanoparticles from NOAA in the workplace
environment. Airborne measurements of carbon nanotubes (CNTs) and carbon nanofibres (CNFs) using
mobility particle sizers also sometimes could present a unique challenge due to the arcing caused by
[11]
the charged airborne CNT and CNF agglomerates in the differential mobility analyser . Although
several groups have attempted to measure and count CNT structures using transmission electron
[12][13]
microscopy or other microscopic methods , there are still no standard methods for measuring
and counting CNT structures. In addition, determining the mass concentration of CNTs and CNFs based
on measuring the elemental carbon (EC) remains a challenge due to other sources of elemental carbon
in the workplace, such as organic composite materials and air and diesel pollution that could interfere
in the determination of CNT and CNF exposures.
Scientific and technical methodologies used to set exposure limits may differ from one entity to
[14]
another, which can lead to disparities in worker protection from country to country . Therefore,
harmonizing the scientific methodologies used in developing OELs, including using the best available
evidence for interspecies extrapolation and specifying the type of data and uncertainties involved in
the OEL determination is necessary for a robust health and safety evaluation framework for NOAAs.
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ISO/TR 18637:2016(E)
This document provides a collaborative, science-based platform to describe and evaluate the state-of-
the-art in such data and methods.
[15]
Current risk assessment methods are likely to apply to NOAAs , although the limited health hazard
data for many NOAAs and the considerable variety in the types of manufactured NOAAs present a
challenge to the efficient development of OELs for individual NOAAs. To date, few OELs and OEBs have
been developed for specific NOAAs and none have been formally regulated by a government agency.
Standard OEL and OEB methodologies for NOAAs are needed to evaluate the evidence on the hazard
potential of NOAAs in the workplace to provide a health basis for risk management decisions, including
selection and evaluation of engineering control options. One of the goals of this document is to identify
both the similarities and differences in the methods used to develop OELs. This evaluation may lead to
improvements in methods for setting exposure limits or bands.
This document presents an overview of the state-of-the-art in the development of OELs and OEBs for
NOAAs. Current approaches for assigning default hazard bands in the absence of NOAA-specific toxicity
data are described. These approaches build on current hazard and control banding strategies, such as
those developed in ISO/TS 12901-2. The current state of the methods and data to develop OELs and
OEBs for NOAAs is described in this document, along with an evaluation of those methods used in
developing the current OELs for NOAAs. Categorical approaches to derive OEBs for NOAAs with limited
data are also discussed, such as those based on biological mode-of-action (MOA) and physico-chemical
(PC) properties. The basis for the framework described in this document is the U.S. NIOSH Current
Intelligence Bulletin Approaches to Developing Occupational Exposure Limits or Bands for Engineered
[16]
Nanomaterials . This document also takes into consideration other state-of-the-science reports,
including outputs of the workshop “Strategies for Setting Occupational Exposure Limits for Engineered
[6]
Nanomaterials,” which was held on September 10-11, 2012 in Washington, DC, USA and the OECD
Working Party on Manufactured Nanomaterials Expert Meeting on Categorization of Manufactured
[17]
Nanomaterials, September 17-19, 2014 .
The primary target audience of this document is occupational safety and health professionals in
government, industry, and academia, who have the expertise to develop OELs or OEBs based on the
guidance in this document. In addition, the evidence-based approach described in this document
may be useful in the evaluation and/or verification of current hazard and control banding schemes
and for identifying the key data gaps. Control banding requires information on both the applicable
hazard category and exposure category. Appropriately verified control banding tools would be broadly
useful, as these tools require less specialized expertise and resources (than for a comprehensive risk
assessment) and are accessible to a wider group of individuals and small businesses. Therefore, this
document can be considered complementary to ISO/TS 12901-2 on control banding for nanomaterials
as it describes the state-of-the-art in the process of assigning nanomaterials to hazard bands/OEBs
when the scientific evidence is not sufficient to develop an individual OEL.
Some of the cited methods lead to results that are not necessarily consistent and this may be due to
method selection biases of the authors. In these cases, diverse results will also make it difficult to use
information to confidently establish exposure and band levels. It is beyond the scope of this document
to attempt to identify the methods which lead to both correct and consistent results. In the event that
methods lead to diverse results, it is hoped that this report will lead to additional methods development
that will lead to improvements and that these improvements can be relied on for setting exposure and
banding levels.
The objectives of this document include
a) describing an evidence-based state-of-the-art framework to develop OELs or OEBs for manufactured
NOAAs, and
b) examining the currently available data and other approaches and methods used (e.g. benchmark
substances and benchmark exposure levels) in the occupational risk management decision-making
for NOAAs.
It is anticipated that this document will contribute to the development of standard hazard and risk
assessment methods and facilitate the systematic evaluation of the potential health risk of occupational
exposure to NOAAs.
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TECHNICAL REPORT ISO/TR 18637:2016(E)
Nanotechnologies — Overview of available frameworks
for the development of occupational exposure limits
and bands for nano-objects and their aggregates and
agglomerates (NOAAs)
1 Scope
This document provides an overview of available methods and procedures for the development of
occupational exposure limits (OELs) and occupational exposure bands (OEBs) for manufactured nano-
objects and their aggregates and agglomerates (NOAAs) for use in occupational health risk management
decision-making.
2 Normative references
There are no normative references in this document.
3 Terms and definitions
For the purposes of this document, the terms and definitions given in ISO/TS 80004-2 and the
following apply.
ISO and IEC maintain terminological databases for use in standardization at the following addresses:
— IEC Electropedia: available at http://www.electropedia.org/
— ISO Online browsing platform: available at http://www.iso.org/obp
3.1
agglomerate
collection of weakly or medium strongly bound particles where the resulting external surface area is
similar to the sum of the surface areas of the individual components
Note 1 to entry: The forces holding agglomerates together are weak forces, for example, van der Waals forces or
simple physical entanglement.
Note 2 to entry: Agglomerates are also termed secondary particles and the original source particles are termed
primary particles.
[SOURCE: ISO 26824:2013, 1.2]
3.2
aggregate
particle comprising strongly bonded or fused particles where the resulting external surface area is
significantly smaller than the sum of surface areas of the individual components
Note 1 to entry: The forces holding an aggregate together are strong forces, for example, covalent or ionic bonds,
or those resulting from sintering or complex physical entanglement, or otherwise combined former primary
particles.
Note 2 to entry: Aggregates are also termed secondary particles and the original source particles are termed
primary particles.
[SOURCE: ISO/TS 80004-2:2015, 3.5]
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ISO/TR 18637:2016(E)
3.3
bulk material
material of the same chemical composition as the NOAA, at a scale greater than the nanoscale
3.4
exposure
contact with a chemical, physical or biological agent by swallowing, breathing, or touching the skin or eyes
Note 1 to entry: Exposure can be short-term (acute exposure), of intermediate duration, or long-term (chronic).
3.5
health hazard
potential source of harm to health
[SOURCE: ISO 10993-17:2002, 3.7]
3.6
health risk
combination of the likelihood of occurrence of harm to health and the severity of that harm
[SOURCE: ISO 10993-17:2002, 3.8]
3.7
nanofibre
nano-object with two external dimensions in the nanoscale and the third dimension significantly larger
Note 1 to entry: The largest external dimension is not necessarily in the nanoscale.
Note 2 to entry: The terms nanofibril and nanofilament can also be used.
Note 3 to entry: See 3.9 Note 1 to entry.
[SOURCE: ISO/TS 80004-2:2015, 4.5]
3.8
nano-object
discrete piece of material with one, two or three external dimensions in the nanoscale
Note 1 to entry: The second and third external dimensions are orthogonal to the first dimension and to each other.
[SOURCE: ISO/TS 80004-1:2010, 2.2]
3.9
nanoparticle
nano-object with all external dimensions in the nanoscale where the lengths of the longest and the
shortest axes of the nano-object do not differ significantly
Note 1 to entry: If the dimensions differ significantly (typically by more than 3 times), terms such as nanofibre or
nanoplate may be preferred to the term nanoparticle.
[SOURCE: ISO/TS 80004-2:2015, 4.4]
3.10
nanoscale
length range approximately from 1 nm to 100 nm
Note 1 to entry: Properties that are not extrapolations from a larger size are predominantly exhibited in this
length range.
[SOURCE: ISO/TS 80004-1:2010, 2.1]
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ISO/TR 18637:2016(E)
3.11
particle
minute piece of matter with defined physical boundaries
Note 1 to entry: A physical boundary can also be described as an interface.
Note 2 to entry: A particle can move as a unit.
Note 3 to entry: This general particle definition applies to nano-objects.
[SOURCE: ISO 26824:2013, 1.1]
3.12
solubility
maximum mass of a nanomaterial that is soluble in a given volume of a particular solvent under
specified conditions
Note 1 to entry: Solubility is expressed in grams per litre of solvent.
[SOURCE: ISO/TR 13014:2012, 2.27]
3.13
occupational exposure limit
maximum concentration of airborne contaminants deemed to be acceptable, as defined by the authority
having jurisdiction
[SOURCE: ISO 16972:2010, 3.133]
3.14
occupational exposure band
quantitative representation of hazard band which describes hazard potential of a particular material
or class of materials in workplace air
3.15
breathing zone
space around the face of a worker from where he or she takes his or her breath
[SOURCE: ISO 24095:2009, 3.1.2.1]
4 Symbols and abbreviated terms
ACGIH American Conference of Governmental Industrial Hygienists
AGS Ausschuss für Gefahrstoffe (German Committee on Hazardous Substances)
AGW Arbeitsplatzgrenzwert (occupational exposure limit)
AIST Japanese National Institute of Advanced Industrial Science and Technology
BALF bronchoalveolar lavage fluid
BAuA Bundesanstalt für Arbeitsschutz und Arbeitsmedizin (German Federal Institute for Occu-
pational Safety and Health)
BEI biological exposure index
BEL benchmark exposure level
BMD benchmark dose
BMDL benchmark dose estimate, 95 % lower confidence limit
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ISO/TR 18637:2016(E)
BSI British Standards Institution
CMAR carcinogenic, mutagenic, asthmagenic, or reproductive toxicant
CNF carbon nanofibre
CNT carbon nanotube
DFG Deutsche Forschungsgemeinschaft (German Research Foundation)
DMEL derived minimum exposure level
DNEL derived no-effect level
EPA United States Environmental Protection Agency
EU European Union
EU-OSHA European Agency for Safety and Health at Work
GBP granular biopersistent particle
GHS Globally Harmonized System of Classification and Labelling of Chemicals
IARC International Agency for Research on Cancer
IFA Institut für Arbeitsschutz (German Institute for Occupational Safety and Health)
ILV indicative limit value
JSOH Japan Society for Occupational Health
LC50 concentration associated with 50 % lethality
LOAEL lowest observed adverse effect level
MAK Maximale Arbeitsplatzkonzentration (maximum workplace concentration)
MOA biological mode of action
MOEL Korean Ministry of Employment and Labour
MSHA United States Mine Safety and Health Administration
MWCNT multi-walled carbon nanotube
NIOSH United States National Institute for Occupational Safety and Health
NOAAs nano-objects, and their aggregates and agglomerates including those larger than 100 nm
NOAEL no observed adverse effect level
NRV nano-reference value
OECD Organization for Economic Cooperation and Development
OEB occupational exposure band
OEL occupational exposure limit
OEL (PL) period-limited occupational exposure limit
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ISO/TR 18637:2016(E)
OELV occupational exposure limit value
OSH occupational safety and health
OSHA United States Occupational Safety and Health Administration
PC physico-chemical
PCM phase contrast microscopy
PEL permissible exposure limit
QRA quantitative risk assessment
REACH Regulation, Evaluation, Authorization and Restriction of Chemicals
REL recommended exposure limit
SCENIHR Scientific Committee on Emerging and Newly Identified Health Risks
SCOEL Scientific Committee on Occupational Exposure Limits
STEL short-term exposure limit
STOT-SE Specific target organ toxicity — single exposure
STOT-RE Specific target organ toxicity — repeated exposure
SWCNT single-walled carbon nanotube
TLV threshold limit value
TSCA Toxic Substances Control Act
TWA time-weighted average
UF ultrafine
VLEP Valeur Limite d’Exposition Professionnelle (occupational exposure limit)
WHO World Health Organization
WHS Work Health and Safety
5 Description of available processes for setting OELs and OEBs
5.1 General considerations
Exposure to substances or mixtures in the workplace can occur through inhalation, absorption through
the skin or ingestion. Most exposure occurs through the inhalation of vapours, dusts, fumes or gases.
For some chemica
...
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