ISO/TR 18637:2016

• Abstract:

  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.

• Status: Published
• Publication Date: 20-Nov-2016
• ICS: 07.030 - Physics. Chemistry
• ICS: 07.120 - Nanotechnologies
• Technical Committee: ISO/TC 229 - Nanotechnologies
• Drafting Committee: ISO/TC 229 - Nanotechnologies
• Current Stage: 6060 - International Standard published
• Start Date: 21-Nov-2016
• Completion Date: 29-Aug-2026

• Consolidated By: ISO 12759-3:2019 - Fans — Efficiency classification for fans — Part 3: Fans without drives at maximum operating speed
• Effective Date: 06-Jun-2022

Overview

ISO/TR 18637:2016 - Nanotechnologies: Overview of available frameworks for the development of occupational exposure limits and bands for nano-objects and their aggregates and agglomerates (NOAAs) - is a Technical Report from ISO/TC 229 that summarizes state-of-the-art methods for deriving occupational exposure limits (OELs) and occupational exposure bands (OEBs) for manufactured nano-objects, aggregates and agglomerates (NOAAs). The document presents an evidence-based framework to support occupational health risk management, hazard communication and control-band decision-making where nano-specific toxicity and exposure data are limited.

Key topics

• Frameworks for OEL/OEB development: description of general processes, evidence-based approaches, and feasibility considerations for setting exposure limits and bands for NOAAs.
• Substance-specific OELs: overview and evaluation of existing OELs for selected nanomaterials (e.g., carbon nanotubes, TiO2, fullerenes) and discussion of data and methodological differences.
• Categorical OELs and read-across: approaches that derive limits for groups of nanomaterials based on physico‑chemical properties and biological mode-of-action.
• Initial/default OEBs and control banding: methods to assign hazard bands/OEBs when specific toxicity data are lacking and integration with control-banding tools.
• Hazard and exposure assessment challenges: practical issues in sampling and measurement (distinguishing background nanoparticles, measurement of CNTs/CNFs, mass vs. particle metrics) and uncertainty in current methods.
• Case studies and evaluation: comparisons of national and organizational approaches (e.g., NIOSH, OECD, national frameworks) and critical analysis of methodological impacts on derived OELs.

Applications

ISO/TR 18637:2016 is intended to:

• Support development and validation of OELs and OEBs for engineered nanomaterials used in industry.
• Inform occupational health risk assessments, exposure monitoring strategies and selection of engineering controls.
• Guide hazard communication and implementation of control-banding approaches where detailed toxicology is unavailable.
• Help harmonize methodological approaches to improve consistency in worker protection across jurisdictions.

Who should use this standard

• Occupational safety and health professionals in government, industry and academia
• Industrial hygienists and risk assessors developing exposure limits or banding schemes
• Regulators and standards developers seeking harmonized methods
• Small- and medium-sized enterprises using control-banding tools to manage nano‑material risks

Related standards

• ISO/TS 12901-2 (control banding for nanomaterials)
• NIOSH Current Intelligence Bulletin approaches and OECD reports on categorization of manufactured nanomaterials

Keywords: ISO/TR 18637:2016, nanotechnologies, occupational exposure limits, OEL, occupational exposure bands, OEB, NOAAs, nano-objects, aggregates, agglomerates, control banding, occupational hygiene, exposure assessment.

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 2016
© ISO 2016, Published in Switzerland
All rights reserved. Unless otherwise specified, no part of this publication may be reproduced or utilized otherwise in any form
or by any means, electronic or mechanical, including photocopying, or posting on the internet or an intranet, without prior
written permission. Permission can be requested from either ISO at the address below or ISO’s member body in the country of
the requester.
ISO copyright office
Ch. de Blandonnet 8 • CP 401
CH-1214 Vernier, Geneva, Switzerland
Tel. [phone]
Fax [phone]
[e-mail]
www.iso.org
ii © ISO 2016 – All rights reserved

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
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.
iv © ISO 2016 – All rights reserved

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.
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.
vi © ISO 2016 – All rights reserved

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]
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]
2 © ISO 2016 – All rights reserved

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
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
4 © ISO 2016 – All rights reserved

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 chemicals, absorption through the skin may also be a significant source of exposure.
The response of the body to exposure from substances and mixtures depends on the nature of the
substance, the health effects it can cause and the amount of the substance or mixture absorbed by the
body. Individuals also have differing abilities to metabolize chemicals which can cause considerable
variation in the toxic effects between people. The extent to which a person is exposed mainly depends
on the concentration of the substance or mixture in the air and the amount of time exposed and, of
course, on the effectiveness of controls. Substances and mixtures may cause immediate acute health
effects or it may be decades before effects on the body become evident.
[18]
Occupational exposure limits are intended to prevent adverse health effects in “nearly all workers”
even with repeated or daily exposures over a working lifetime. Some OELs are based on health effects
data only (e.g. ACGIH TLV), and other OELs also include consideration of the technological feasibility
(e.g. NIOSH RELs) or economic feasibility (e.g. OSHA PEL) of measuring and controlling exposures.
For a few substances, usually the more potent probable and established human carcinogens, it is not
currently possible to assign an appropriate exposure limit. For these substances, exposure should be
controlled to the lowest practicable level. Biological monitoring may provide a more reliable indication
of workplace exposure for these substances.
The evaluation of hazards posed by atmospheric contaminants in the working environment is often
a complex task, taking into account the potentially large variability of exposure at the workplace
requiring sound occupational hygiene exposure assessment strategies. For this reason, it is essential
that those persons responsible for such assessments are knowledgeable and experienced professionals,
who are fully aware of all issues canvassed in this document and have appropriate qualifications and
experience in occupational hygiene.
NOTE A knowledgeable and experienced professional is an individual who will properly perform a specific
job. This person utilizes a combination of knowledge, skills and behaviour to improve performance. More
generally, competence is the state or quality of being adequately or well qualified, having the ability to perform a
[3]
specific role .
The relationship between various exposure limits should not be used as a general measure of their
relative toxicity. This is because, among other things, the values for different substances are often
established with regard to different biological effects, such as irritation or systemic toxicity. Similarly,
the exposure limits should not be used as a basis for the evaluation of community air quality, or for long
term, non-occupational exposures.
Most substances used in industry have not been assigned exposure limits. This does not imply that
these substances are safe or non-hazardous. In many cases there is insufficient information on the
health effects of these unlisted substances to allow national regulatory bodies to assign an exposure
limit, even on a tentative basis. In other instances, the use of the substance does not lead to significant
airborne levels of contaminant, or its use is so restricted that an exposure limit is not warranted.
It is a good general policy to keep the exposure to any substance as low as is practicable, irrespective of
whether present information indicates it is hazardous or not. Some substances previously thought to be
comparatively safe have subsequently been found to pose serious long term health risks.
There are three types of exposure limits:
— time-weighted average (TWA) limit;
— short term exposure limit (STEL);
— peak or ceiling limit.
These limits and other technical aspects of setting OELs are further described in A.1.2.
5.2 Description of evidence-based process
[5]
The methods for developing OELs depend on the available data. Schulte, et al. describe three general
scenarios for varying amounts of toxicological data. This framework was refined to describe linkages
between the evidence basis for these general categories through benchmark substances. Benchmark
substances are well-characterized materials (e.g. airborne particles or fibres) with sufficient dose-
response data from animal and/or human studies to develop quantitative risk estimates and health-
[19][20]
based OELs (Figure 1) . Benchmark materials also provide a reference (e.g. as a positive or
negative control) in comparative toxicity assays with new NOAAs that have limited toxicological data
[19][20][21]
but similar physico-chemical properties and inferred biological mode-of-action (MOA) . The
focus of this document is on occupational airborne exposures to nanomaterials since inhalation is the
major route of exposure to potentially hazardous substances, including NOAAs, in the workplace.
6 © ISO 2016 – All rights reserved

As shown in Figure 1, in the first case, if dose-response data are sufficient, an OEL for an individual NOAA
can be developed using quantitative risk assessment (QRA). The definition of sufficient will ultimately
be based on a judgment about the available data, and may include weight of evidence evaluations,
[22]
including the availability of adequate data for benchmark dose modelling or no observed adverse
effect levels (NOAELs) or lowest observed adverse effect levels (LOAEL) from well-conducted studies.
Second, if data are insufficient for QRA for a specific substance, but adequate information is available
on a similar substance in the same mode-of-action category, then a categorical OEL may be assigned
by qualitative or quantitative methods including read-across and structure-bioactivity modelling, with
comparisons between NOAAs and benchmark substances. Third, if data are insufficient to develop a
substance-specific or categorical OEL, then initial (default) hazard and control bands may be derived
by comparing NOAA properties to that of similar materials in broad categories. The objective of this
evidence-based approach is to facilitate decision-making about exposure control strategies for NOAAs
in the workplace based on best available evidence. The framework allows for iteration and revision of an
OEB or OEL as new data become available based on standard criteria for data and methods. At this time,
more examples of OELs developed for NOAAs are available than of categorical OELs or OEBs for NOAAs.
The data available for developing OELs or OEBs for NOAAs may include
a) data from in vivo and in vitro testing of specific NOAAs (e.g. from the OECD testing program,
manufacturers of NOAAs, and non-regulatory government agencies such as the NIOSH and the NTP
in the US), and
b) existing toxicology or epidemiology studies of lung effects from inhaled particles and fibres for
comparative toxicity analyses.
[23]
General chemical hazard databases (e.g. as used in GHS hazard classification) are also available for
some of the parent or bulk materials with similar chemical composition to the NOAA for use in hazard
band/OEB allocation and control banding (e.g. see ISO/TS 12901-2). Table 1 summarizes the type of
data and methods needed to develop OELs or OEBs.
Figure 1 — Evidence-based strategy to develop exposure control limits and bands for NOAAs,
based on level of evidence
Table 1 — Data and methods needed to develop exposure limits or bands
Guidance value Level of evidence Data, analysis tools and methods
Substance-specific OEL Sufficient Substance-specific dose-response data for quantitative
risk assessment; availability of substance-specific sam-
pling and analytical method
Categorical OEL Limited (focused) Comparative toxicity, clustering and categorization
to estimate hazard or risk based on physico-chemical
properties and biological mode-of-action data
OEB Minimal or inadequate Analogy; default hazard categories and exposure con-
trol options are applied.
5.3 Substance-specific OELs
The substance-specific OELs typically do not take separate account of the nanoparticle size, although
some of these OELs do specify the particle size sampling criteria associated with regional respiratory
tract deposition. These sampling criteria include inhalable (total), thoracic (airways), and respirable
(pulmonary) size fractions. Nanoparticles are capable of depositing anywhere in the respiratory tract
region, including the pulmonary region where gas exchange takes place. Some of the individual OELs
are specific to the dust and/or fume forms, and fumes by nature consist of nanostructured particles.
The OELs for fumes may be lower mass concentrations than the OELs for dust of the same chemical
3 3
substance (e.g. the NIOSH REL and OSHA PEL for copper is 1 mg/m for the dust and 0,1 mg/m for the
[24] 3
fume) . In other cases the OEL applies to both the dust and fume (e.g. iron oxide, NIOSH REL is 5 mg/m
3 3
and OSHA PEL is 10 mg/m ; cobalt metal dust and fume, NIOSH REL is 0,05 mg/m and the OSHA PEL
is 0,1 mg/m ). It is relevant to note that those OELs vary at least as much by chemical composition as by
descriptors of particle size (dust, solid particles generated by any mechanical processing of materials
such as crushing, grinding, and handling or fume, airborne dispersion consisting of small solid particles
created by condensation from the gaseous state).
Clause 6 and Table 2 provide a description and list of the OELs that have been developed for
specific nanomaterials by non-regulatory government agencies, companies, and nongovernmental
organizations. To date, no regulatory standards have been circulated for NOAAs.
5.4 Categorical OELs
Historically, many airborne particulate materials were regarded as a “nuisance” or as “low toxicity”
dusts and categorical OELs, such as a generic inhalable OEL of 10 mg/m and a respirable OEL of
4 mg/m were set for many low-toxicity poorly-soluble dusts including aluminium oxides, graphite,
[25]
titanium dioxide and others . In Germany, the DFG MAK commission recently reduced the OEL for
3 3
biopersistent granular particles from 3 mg/m to 0,3 mg/m (respirable fraction), reflecting concerns
[26]
about a possible carcinogenic potential for this category of substances . All these values, however,
were not intended for particulate materials with specific known inhalation or systemic toxicity
(e.g. asbestos and lead, respectively) for which substance-specific OELs were also determined.
Advantages of categorical approaches include:
— more efficient use of data;
— reduced costs;
— reduced animal use;
— increased sample size;
— greater robustness of results;
[27]
— increased biological plausibility for other materials in the same mode of action category .
Categorical approaches are compatible with hazard and risk assessment frameworks proposed for
[29]
NOAAs (e.g. References [5], [20] and [28]) and with a standard risk assessment paradigm . Methods
8 © ISO 2016 – All rights reserved

to derive OELs for NOAAs using categorical approaches may include quantitative or qualitative read-
[27]
across ; comparative potency analyses of NOAAs to benchmark (reference) particles in the same
[19][20] [19][30][31][32]
mode-of-action (MOA) category , e.g. using a “parallelogram” approach ; and
assigning an untested substance to the low end of the distribution of OELs for materials in the same
[33]
hazard class .
Other risk analysis and categorization approaches include both occupational and environmental
[34][35]
components, such as screening tools of potential risks over the NOAA lifecycle . The multi-criteria
decision analysis (MCDA) approach includes evaluation of the risks and benefits with weightings
[28]
obtained through expert elicitation . This process has been used to assign NOAAs to qualitative risk
[36]
categories (low, medium, high) .
Clause 7 summarizes the categorical OELs that have been proposed by governmental and
nongovernmental organizations. These categories are based on broad groups of physico-chemical
properties that influence toxicity (soluble, biopersistent low toxicity, biopersistent high toxicity, and
fibres). The BSI and IFA categories are provisional exposure limits based on existing OELs for particles
and fibres in these categories, which includes in some cases a precautionary downward adjustment for
the nanoscale form. The extent to which chemical substance-specific data are available would allow
refinement of the categorical OELs to an individual OEL that may be more applicable to an individual
substance.
5.5 Initial or default occupational exposure bands
When data are not sufficient to develop an individual OEL, hazard banding approaches are often used
[5]
to facilitate decision-making among engineering control options . Control banding typically utilizes a
[37][38][39]
matrix approach to categorize substances according to their hazard and exposure potential
[40][41][42]
to determine an appropriate control technology (such as general ventilation, local exhaust,
[39][41][42][43]
or containment) . The combination of the selected hazard and exposure bands determines
the control band and associated engineering control options. However, the utility of such an approach
is frequently limited by the availability of adequate toxicological data for use in hazard assessment. The
absence of such data makes workplace risk characterization and the subsequent selection of appropriate
control measures problematic. Another suggested approach is the utilization of initial default hazard
categories or OEBs for NOAAs based on the physico-chemical properties associated with point-of-entry
or systemic toxicity, including particle surface chemistry and area, shape, diameter, and solubility, as
well as any evidence on the mutagenicity, carcinogenicity, or reproductive toxicity of the nanomaterial
[20][42][44][45][46]
or parent material .
ISO/TS 12901-2 also incorporates available toxicological information and physico-chemical properties
to designate nanomaterials into hazard bands. In this method, nanomaterials are grouped into one
of five inhalation hazard groups (A to E) according to increasing severity described in GHS hazard
[23]
classification applicable to chemicals .
3 3
— Category A (no significant risk to health) corresponds to an OEB of 1 mg/m to 10 mg/m (as 8 h
time-weighted average)
3 3
— Category B (slight hazard; slightly toxic) — 0,1 mg/m to 1 mg/m
3 3
— Category C (moderate hazard) — 0,01 mg/m to 0,1 mg/m
— Category D (serious
...

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 2016
© ISO 2016, Published in Switzerland
All rights reserved. Unless otherwise specified, no part of this publication may be reproduced or utilized otherwise in any form
or by any means, electronic or mechanical, including photocopying, or posting on the internet or an intranet, without prior
written permission. Permission can be requested from either ISO at the address below or ISO’s member body in the country of
the requester.
ISO copyright office
Ch. de Blandonnet 8 • CP 401
CH-1214 Vernier, Geneva, Switzerland
Tel. [phone]
Fax [phone]
[e-mail]
www.iso.org
ii © ISO 2016 – All rights reserved

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
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.
iv © ISO 2016 – All rights reserved

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.
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.
vi © ISO 2016 – All rights reserved

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]
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]
2 © ISO 2016 – All rights reserved

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
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
4 © ISO 2016 – All rights reserved

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 chemicals, absorption through the skin may also be a significant source of exposure.
The response of the body to exposure from substances and mixtures depends on the nature of the
substance, the health effects it can cause and the amount of the substance or mixture absorbed by the
body. Individuals also have differing abilities to metabolize chemicals which can cause considerable
variation in the toxic effects between people. The extent to which a person is exposed mainly depends
on the concentration of the substance or mixture in the air and the amount of time exposed and, of
course, on the effectiveness of controls. Substances and mixtures may cause immediate acute health
effects or it may be decades before effects on the body become evident.
[18]
Occupational exposure limits are intended to prevent adverse health effects in “nearly all workers”
even with repeated or daily exposures over a working lifetime. Some OELs are based on health effects
data only (e.g. ACGIH TLV), and other OELs also include consideration of the technological feasibility
(e.g. NIOSH RELs) or economic feasibility (e.g. OSHA PEL) of measuring and controlling exposures.
For a few substances, usually the more potent probable and established human carcinogens, it is not
currently possible to assign an appropriate exposure limit. For these substances, exposure should be
controlled to the lowest practicable level. Biological monitoring may provide a more reliable indication
of workplace exposure for these substances.
The evaluation of hazards posed by atmospheric contaminants in the working environment is often
a complex task, taking into account the potentially large variability of exposure at the workplace
requiring sound occupational hygiene exposure assessment strategies. For this reason, it is essential
that those persons responsible for such assessments are knowledgeable and experienced professionals,
who are fully aware of all issues canvassed in this document and have appropriate qualifications and
experience in occupational hygiene.
NOTE A knowledgeable and experienced professional is an individual who will properly perform a specific
job. This person utilizes a combination of knowledge, skills and behaviour to improve performance. More
generally, competence is the state or quality of being adequately or well qualified, having the ability to perform a
[3]
specific role .
The relationship between various exposure limits should not be used as a general measure of their
relative toxicity. This is because, among other things, the values for different substances are often
established with regard to different biological effects, such as irritation or systemic toxicity. Similarly,
the exposure limits should not be used as a basis for the evaluation of community air quality, or for long
term, non-occupational exposures.
Most substances used in industry have not been assigned exposure limits. This does not imply that
these substances are safe or non-hazardous. In many cases there is insufficient information on the
health effects of these unlisted substances to allow national regulatory bodies to assign an exposure
limit, even on a tentative basis. In other instances, the use of the substance does not lead to significant
airborne levels of contaminant, or its use is so restricted that an exposure limit is not warranted.
It is a good general policy to keep the exposure to any substance as low as is practicable, irrespective of
whether present information indicates it is hazardous or not. Some substances previously thought to be
comparatively safe have subsequently been found to pose serious long term health risks.
There are three types of exposure limits:
— time-weighted average (TWA) limit;
— short term exposure limit (STEL);
— peak or ceiling limit.
These limits and other technical aspects of setting OELs are further described in A.1.2.
5.2 Description of evidence-based process
[5]
The methods for developing OELs depend on the available data. Schulte, et al. describe three general
scenarios for varying amounts of toxicological data. This framework was refined to describe linkages
between the evidence basis for these general categories through benchmark substances. Benchmark
substances are well-characterized materials (e.g. airborne particles or fibres) with sufficient dose-
response data from animal and/or human studies to develop quantitative risk estimates and health-
[19][20]
based OELs (Figure 1) . Benchmark materials also provide a reference (e.g. as a positive or
negative control) in comparative toxicity assays with new NOAAs that have limited toxicological data
[19][20][21]
but similar physico-chemical properties and inferred biological mode-of-action (MOA) . The
focus of this document is on occupational airborne exposures to nanomaterials since inhalation is the
major route of exposure to potentially hazardous substances, including NOAAs, in the workplace.
6 © ISO 2016 – All rights reserved

As shown in Figure 1, in the first case, if dose-response data are sufficient, an OEL for an individual NOAA
can be developed using quantitative risk assessment (QRA). The definition of sufficient will ultimately
be based on a judgment about the available data, and may include weight of evidence evaluations,
[22]
including the availability of adequate data for benchmark dose modelling or no observed adverse
effect levels (NOAELs) or lowest observed adverse effect levels (LOAEL) from well-conducted studies.
Second, if data are insufficient for QRA for a specific substance, but adequate information is available
on a similar substance in the same mode-of-action category, then a categorical OEL may be assigned
by qualitative or quantitative methods including read-across and structure-bioactivity modelling, with
comparisons between NOAAs and benchmark substances. Third, if data are insufficient to develop a
substance-specific or categorical OEL, then initial (default) hazard and control bands may be derived
by comparing NOAA properties to that of similar materials in broad categories. The objective of this
evidence-based approach is to facilitate decision-making about exposure control strategies for NOAAs
in the workplace based on best available evidence. The framework allows for iteration and revision of an
OEB or OEL as new data become available based on standard criteria for data and methods. At this time,
more examples of OELs developed for NOAAs are available than of categorical OELs or OEBs for NOAAs.
The data available for developing OELs or OEBs for NOAAs may include
a) data from in vivo and in vitro testing of specific NOAAs (e.g. from the OECD testing program,
manufacturers of NOAAs, and non-regulatory government agencies such as the NIOSH and the NTP
in the US), and
b) existing toxicology or epidemiology studies of lung effects from inhaled particles and fibres for
comparative toxicity analyses.
[23]
General chemical hazard databases (e.g. as used in GHS hazard classification) are also available for
some of the parent or bulk materials with similar chemical composition to the NOAA for use in hazard
band/OEB allocation and control banding (e.g. see ISO/TS 12901-2). Table 1 summarizes the type of
data and methods needed to develop OELs or OEBs.
Figure 1 — Evidence-based strategy to develop exposure control limits and bands for NOAAs,
based on level of evidence
Table 1 — Data and methods needed to develop exposure limits or bands
Guidance value Level of evidence Data, analysis tools and methods
Substance-specific OEL Sufficient Substance-specific dose-response data for quantitative
risk assessment; availability of substance-specific sam-
pling and analytical method
Categorical OEL Limited (focused) Comparative toxicity, clustering and categorization
to estimate hazard or risk based on physico-chemical
properties and biological mode-of-action data
OEB Minimal or inadequate Analogy; default hazard categories and exposure con-
trol options are applied.
5.3 Substance-specific OELs
The substance-specific OELs typically do not take separate account of the nanoparticle size, although
some of these OELs do specify the particle size sampling criteria associated with regional respiratory
tract deposition. These sampling criteria include inhalable (total), thoracic (airways), and respirable
(pulmonary) size fractions. Nanoparticles are capable of depositing anywhere in the respiratory tract
region, including the pulmonary region where gas exchange takes place. Some of the individual OELs
are specific to the dust and/or fume forms, and fumes by nature consist of nanostructured particles.
The OELs for fumes may be lower mass concentrations than the OELs for dust of the same chemical
3 3
substance (e.g. the NIOSH REL and OSHA PEL for copper is 1 mg/m for the dust and 0,1 mg/m for the
[24] 3
fume) . In other cases the OEL applies to both the dust and fume (e.g. iron oxide, NIOSH REL is 5 mg/m
3 3
and OSHA PEL is 10 mg/m ; cobalt metal dust and fume, NIOSH REL is 0,05 mg/m and the OSHA PEL
is 0,1 mg/m ). It is relevant to note that those OELs vary at least as much by chemical composition as by
descriptors of particle size (dust, solid particles generated by any mechanical processing of materials
such as crushing, grinding, and handling or fume, airborne dispersion consisting of small solid particles
created by condensation from the gaseous state).
Clause 6 and Table 2 provide a description and list of the OELs that have been developed for
specific nanomaterials by non-regulatory government agencies, companies, and nongovernmental
organizations. To date, no regulatory standards have been circulated for NOAAs.
5.4 Categorical OELs
Historically, many airborne particulate materials were regarded as a “nuisance” or as “low toxicity”
dusts and categorical OELs, such as a generic inhalable OEL of 10 mg/m and a respirable OEL of
4 mg/m were set for many low-toxicity poorly-soluble dusts including aluminium oxides, graphite,
[25]
titanium dioxide and others . In Germany, the DFG MAK commission recently reduced the OEL for
3 3
biopersistent granular particles from 3 mg/m to 0,3 mg/m (respirable fraction), reflecting concerns
[26]
about a possible carcinogenic potential for this category of substances . All these values, however,
were not intended for particulate materials with specific known inhalation or systemic toxicity
(e.g. asbestos and lead, respectively) for which substance-specific OELs were also determined.
Advantages of categorical approaches include:
— more efficient use of data;
— reduced costs;
— reduced animal use;
— increased sample size;
— greater robustness of results;
[27]
— increased biological plausibility for other materials in the same mode of action category .
Categorical approaches are compatible with hazard and risk assessment frameworks proposed for
[29]
NOAAs (e.g. References [5], [20] and [28]) and with a standard risk assessment paradigm . Methods
8 © ISO 2016 – All rights reserved

to derive OELs for NOAAs using categorical approaches may include quantitative or qualitative read-
[27]
across ; comparative potency analyses of NOAAs to benchmark (reference) particles in the same
[19][20] [19][30][31][32]
mode-of-action (MOA) category , e.g. using a “parallelogram” approach ; and
assigning an untested substance to the low end of the distribution of OELs for materials in the same
[33]
hazard class .
Other risk analysis and categorization approaches include both occupational and environmental
[34][35]
components, such as screening tools of potential risks over the NOAA lifecycle . The multi-criteria
decision analysis (MCDA) approach includes evaluation of the risks and benefits with weightings
[28]
obtained through expert elicitation . This process has been used to assign NOAAs to qualitative risk
[36]
categories (low, medium, high) .
Clause 7 summarizes the categorical OELs that have been proposed by governmental and
nongovernmental organizations. These categories are based on broad groups of physico-chemical
properties that influence toxicity (soluble, biopersistent low toxicity, biopersistent high toxicity, and
fibres). The BSI and IFA categories are provisional exposure limits based on existing OELs for particles
and fibres in these categories, which includes in some cases a precautionary downward adjustment for
the nanoscale form. The extent to which chemical substance-specific data are available would allow
refinement of the categorical OELs to an individual OEL that may be more applicable to an individual
substance.
5.5 Initial or default occupational exposure bands
When data are not sufficient to develop an individual OEL, hazard banding approaches are often used
[5]
to facilitate decision-making among engineering control options . Control banding typically utilizes a
[37][38][39]
matrix approach to categorize substances according to their hazard and exposure potential
[40][41][42]
to determine an appropriate control technology (such as general ventilation, local exhaust,
[39][41][42][43]
or containment) . The combination of the selected hazard and exposure bands determines
the control band and associated engineering control options. However, the utility of such an approach
is frequently limited by the availability of adequate toxicological data for use in hazard assessment. The
absence of such data makes workplace risk characterization and the subsequent selection of appropriate
control measures problematic. Another suggested approach is the utilization of initial default hazard
categories or OEBs for NOAAs based on the physico-chemical properties associated with point-of-entry
or systemic toxicity, including particle surface chemistry and area, shape, diameter, and solubility, as
well as any evidence on the mutagenicity, carcinogenicity, or reproductive toxicity of the nanomaterial
[20][42][44][45][46]
or parent material .
ISO/TS 12901-2 also incorporates available toxicological information and physico-chemical properties
to designate nanomaterials into hazard bands. In this method, nanomaterials are grouped into one
of five inhalation hazard groups (A to E) according to increasing severity described in GHS hazard
[23]
classification applicable to chemicals .
3 3
— Category A (no significant risk to health) corresponds to an OEB of 1 mg/m to 10 mg/m (as 8 h
time-weighted average)
3 3
— Category B (slight hazard; slightly toxic) — 0,1 mg/m to 1 mg/m
3 3
— Category C (moderate hazard) — 0,01 mg/m to 0,1 mg/m
— Category D (serious
...

RAPPORT ISO/TR
TECHNIQUE 18637
Première édition
2016-12
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)
Nanotechnologies — Overview of available frameworks for the
development of occupational exposure limits and bands for nano-
objects and their aggregates and agglomerates (NOAAs)
Numéro de référence
©
ISO 2016
DOCUMENT PROTÉGÉ PAR COPYRIGHT
© ISO 2016, Publié en Suisse
Droits de reproduction réservés. Sauf indication contraire, aucune partie de cette publication ne peut être reproduite ni utilisée
sous quelque forme que ce soit et par aucun procédé, électronique ou mécanique, y compris la photocopie, l’affichage sur
l’internet ou sur un Intranet, sans autorisation écrite préalable. Les demandes d’autorisation peuvent être adressées à l’ISO à
l’adresse ci-après ou au comité membre de l’ISO dans le pays du demandeur.
ISO copyright office
Ch. de Blandonnet 8 • CP 401
CH-1214 Vernier, Geneva, Switzerland
Tel. [phone]
Fax [phone]
[e-mail]
www.iso.org
ii © ISO 2016 – Tous droits réservés

Sommaire Page
Avant-propos .iv
Introduction .v
1 Domaine d’application . 1
2 Références normatives . 1
3 Termes et définitions . 1
4 Symboles et abréviations . 3
5 Description des processus disponibles pour la définition des VLEP et des BEP .6
5.1 Considérations générales . 6
5.2 Description du processus basé sur la preuve . 7
5.3 VLEP spécifiques à la substance . 8
5.4 VLEP catégorielles. 9
5.5 Bandes d’exposition professionnelle initiales ou par défaut .10
6 VLEP spécifiques à la substance pour les nanomatériaux .10
6.1 Présentation générale .10
6.2 VLEP spécifiques à la substance disponibles .11
6.2.1 Nanotubes de carbone .11
6.2.2 TiO à l’échelle nanométrique .12
6.2.3 Fullerènes . .13
6.3 Évaluation des méthodes d’établissement de VLEP .13
6.3.1 Similarités et différences .13
6.3.2 Influence de la méthode sur les VLEP dérivées pour les nanomatériaux . .14
6.3.3 État de la science en soutien aux méthodes d’évaluation des risques pour
les VLEP de nanomatériaux .16
7 VLEP catégorielles pour les nanomatériaux .16
7.1 Récapitulatif des options proposées .16
7.1.1 Royaume-Uni .16
7.1.2 Allemagne .16
7.1.3 Approche des États-Unis (NIOSH) .18
7.1.4 Approches du Japon (AIST) .18
7.1.5 OCDE . .20
7.2 Évaluation des VLEP catégorielles .21
7.2.1 Similarités et différences .21
7.2.2 État des connaissances sous-jacentes aux VLEP catégorielles .22
8 BEP et gestion graduée des risques pour les nanomatériaux .23
8.1 Présentation des schémas actuels de gestion graduée des dangers et des risques .23
8.1.1 Comparaison des bandes de danger et des BEP appliquées aux NOAA inhalés.25
8.1.2 Schéma de gestion graduée des dangers pour NOAA de l’ISO .28
8.2 Études de cas de gestion graduée des NOAA .29
8.3 Évaluation de la preuve pour les BEP initiales (par défaut) pour les catégories de NOAA 31
8.3.1 Analyses catégorielles et lecture croisée .31
8.3.2 Utilité des données in vitro dans le développement de VLEP/BEP pour
les NOAA . .32
8.3.3 Options de dérivation d’une VLEP ou d’une BEP pour les NOAA .33
9 Considérations sur la faisabilité du processus de définition de VLEP et de BEP .34
Annexe A (informative) Processus normalisés de définition de VLEP .35
Bibliographie .68
Avant-propos
L'ISO (Organisation internationale de normalisation) est une fédération mondiale d'organismes
nationaux de normalisation (comités membres de l'ISO). L'élaboration des Normes internationales est
en général confiée aux comités techniques de l'ISO. Chaque comité membre intéressé par une étude
a le droit de faire partie du comité technique créé à cet effet. Les organisations internationales,
gouvernementales et non gouvernementales, en liaison avec l'ISO participent également aux travaux.
L'ISO collabore étroitement avec la Commission électrotechnique internationale (IEC) en ce qui
concerne la normalisation électrotechnique.
Les procédures utilisées pour élaborer le présent document et celles destinées à sa mise à jour sont
décrites dans les Directives ISO/IEC, Partie 1. Il convient, en particulier de prendre note des différents
critères d'approbation requis pour les différents types de documents ISO. Le présent document a été
rédigé conformément aux règles de rédaction données dans les Directives ISO/IEC, Partie 2 (voir www.
iso.org/directives).
L'attention est attirée sur le fait que certains des éléments du présent document peuvent faire l'objet de
droits de propriété intellectuelle ou de droits analogues. L'ISO ne saurait être tenue pour responsable
de ne pas avoir identifié de tels droits de propriété et averti de leur existence. Les détails concernant
les références aux droits de propriété intellectuelle ou autres droits analogues identifiés lors de
l'élaboration du document sont indiqués dans l'Introduction et/ou dans la liste des déclarations de
brevets reçues par l'ISO (voir www.iso.org/brevets).
Les appellations commerciales éventuellement mentionnées dans le présent document sont données
pour information, par souci de commodité, à l’intention des utilisateurs et ne sauraient constituer un
engagement.
Pour une explication de la nature volontaire des normes, la signification des termes et expressions
spécifiques de l'ISO liés à l'évaluation de la conformité, ou pour toute information au sujet de l'adhésion
de l'ISO aux principes de l’Organisation mondiale du commerce (OMC) concernant les obstacles
techniques au commerce (OTC), voir le lien suivant: www.iso.org/avant-propos.
Le comité chargé de l'élaboration du présent document est l'ISO/TC 229, Nanotechnologies.
iv © ISO 2016 – Tous droits réservés

Introduction
Les nano-objets et leurs agrégats et agglomérats (NOAA) représentent un sous-ensemble de matériaux
particulaires qui peuvent être dispersés dans l’air et peuvent constituer un risque pour la santé par
le biais de l’exposition par inhalation. Les NOAA comprennent des structures présentant une, deux
ou trois dimensions externes à l’échelle nanométrique, comprises approximativement entre 1 nm et
100 nm, pouvant être des sphères, des fibres, des tubes et autres en tant que structures primaires.
Les NOAA peuvent être constitués de structures primaires individuelles à l’échelle nanométrique et de
structures agrégées ou agglomérées, y compris de tailles supérieures à 100 nm. Un agrégat comprend
des particules (structures) fortement liées ou fusionnées. Un agglomérat est un ensemble de particules
[1][2][3][4]
(structures) faiblement liées .
L’objet du présent document est de décrire un cadre général pour la définition de valeurs limites
d’exposition professionnelle (VLEP) ou de bandes d’exposition professionnelle (BEP) pour des NOAA
individuels ou des catégories de NOAA pour lesquels il existe différents niveaux de disponibilité des
données. Les VLEP et les BEP sont des outils importants de prévention des maladies professionnelles.
Les VLEP sont utilisées depuis longtemps dans l’hygiène industrielle et sont basées sur l’observation
des travailleurs ou sur des études réalisées sur des animaux de laboratoire. Les VLEP sont établies dans
le but de réduire au minimum la probabilité d’effets indésirables dus à l’exposition à des substances
[5][6]
potentiellement dangereuses sur le lieu de travail. Une VLEP est généralement spécifique d’une
substance (bien que parfois exprimée de façon générique, comme pour la poussière). Les données de
développement d’une VLEP peuvent être insuffisantes, en particulier pour les substances telles que
[7][8][9]
les NOAA utilisés dans les technologies émergentes. La gestion graduée des dangers est utilisée
depuis de nombreuses années pour aider aux décisions de communication des dangers et de contrôle
de l’exposition pour les substances sans VLEP. Les substances sont affectées à une bande de danger
sur la base des données de toxicité limitées provenant généralement d’études sur les animaux. Les
schémas de gestion graduée des dangers consistent généralement en bandes qualitatives allant d’effets
de gravité faible à élevée. Ainsi, une bande de danger représente une plage de toxicités potentielles
pour une substance particulière ou une catégorie de substances. Certains schémas de gestion graduée
[10]
des dangers incluent des BEP associées. Le terme BEP est un terme général pour les plages de
concentration d’exposition utilisées dans certains schémas de gestion graduée des dangers qui sont
associés aux plages de dangers potentiels. À l’inverse d’une VLEP, une bande d’exposition est une plage
de concentrations potentielles d’une substance (ou d’une catégorie de substances) à laquelle le personnel
peut être exposé dans un scénario défini sur le lieu de travail et qui est basée sur des facteurs tels que la
quantité de NOAA traités ou utilisés, la nature du processus et la forme du NOAA, y compris l’aptitude à
[3]
l’empoussièrement. Dans la gestion graduée des risques, la bande de danger et la bande d’exposition
sont combinées pour déterminer la bande de risque pour tout scénario professionnel particulier (p. ex.
ISO/TS 12901-2).
Les VLEP et les BEP font partie d’un programme général de santé et de sécurité au travail (SST) et
ne sont pas destinées à identifier et traiter tous les risques pour la santé et la sécurité associés à un
processus ou une tâche spécifique. Les VLEP et les BEP sont destinées à fournir aux professionnels de
la santé et de la sécurité au travail une base permettant d’évaluer l’efficacité des contrôles d’exposition
et autres pratiques de gestion du risque. L’évaluation de l’exposition des nanomatériaux dont les
nanomatériaux carbonés [comme le fullerène, le graphène, le nanotube de carbone à paroi simple
(SWCNT) et le nanotube de carbone à parois multiples (MWCNT)], les oxydes métalliques (le TiO ,
SiO , l’oxyde de zinc, l’oxyde de fer) et les métaux (nanoparticules d’argent et d’or) reste complexe dans
le domaine de l’hygiène professionnelle, car il existe relativement peu d’études sur la caractérisation
des expositions aux NOAA sur les lieux de travail. Des méthodes analytiques et d’échantillonnage
permettant de mesurer avec exactitude les nanomatériaux sont toujours en cours d’élaboration. La
plupart des dispositifs d’échantillonnage qui mesurent les concentrations de particules en suspension
dans l’air, comme les compteurs de particules à condensation et les compteurs de particules optiques,
ne peuvent pas différencier les expositions ambiantes et les nanoparticules de fond des NOAA dans
l’environnement de travail. Les mesurages de nanotubes de carbone (NTC) et de nanofibres de carbone
(NFC) en suspension dans l’air utilisant des analyseurs de mobilité électrique peuvent également
quelquefois présenter un problème particulier dû à la formation d’arc causée par les agglomérats du NTC
[11]
ou de la NFC en suspension chargés dans l’analyseur de mobilité différentielle. Bien que plusieurs
groupes aient tenté de mesurer et de compter les structures de NTC au moyen de la microscopie
[12][13]
électronique à transmission et autres méthodes de microscopie, il n’existe toujours pas de
méthode normalisée de mesure et de comptage des structures de NTC. De plus, la détermination de la
concentration massique des NTC et des NFC sur la base de la mesure du carbone élémentaire (CE) reste
complexe en raison d’autres sources de carbone élémentaire sur le lieu de travail, comme les matériaux
composites organiques et la pollution atmosphérique et par toute source de combustion qui peuvent
interférer dans la détermination des expositions aux NTC et aux NFC.
Les méthodologies scientifiques et techniques utilisées pour définir les limites d’exposition peuvent
différer d’une entité à une autre, ce qui peut entraîner des disparités dans la protection du personnel
[14]
d’un pays à l’autre. Par conséquent, l’harmonisation des méthodologies scientifiques utilisées dans le
développement des VLEP, comprenant l’utilisation de la meilleure preuve disponible pour l’extrapolation
interespèces et la spécification du type de données et des incertitudes impliquées par la détermination
des VLEP, est nécessaire pour obtenir un cadre robuste d’évaluation de la santé et de la sécurité pour les
NOAA. Le présent document propose une plateforme collaborative scientifique permettant de décrire
et d’évaluer ces données et méthodes de l’actuel état de l’art.
[15]
Les méthodes actuelles d’évaluation des risques sont susceptibles de s’appliquer aux NOAA, même
si les données limitées sur les risques pour la santé de nombreux NOAA et la considérable diversité des
types de NOAA manufacturés présentent un défi pour le développement efficace de VLEP pour chaque
NOAA individuel. À ce jour, quelques VLEP et BEP ont été développées pour des NOAA spécifiques
et aucune n’a été formellement réglementée par une agence gouvernementale. Des méthodologies
d’établissement de VLEP et de BEP normalisées pour les NOAA sont nécessaires pour évaluer la preuve
du danger potentiel des NOAA sur le lieu de travail afin de fournir une base pour les décisions de gestion
du risque, comprenant la sélection et l’évaluation des options de contrôle d’ingénierie. L’un des objectifs
du présent document consiste à identifier à la fois les similarités et les différences entre les méthodes
utilisées pour développer les VLEP. Cette évaluation peut mener à des améliorations dans les méthodes
de définition des valeurs limites ou des bandes d’exposition.
Le présent document fournit une présentation générale de l’actuel état de l’art en matière de
développement des VLEP et des BEP pour les NOAA. Les approches actuelles d’attribution des bandes
de danger par défaut en l’absence de données de toxicité spécifiques des NOAA sont décrites. Ces
approches s’appuient sur les stratégies actuelles de gestion graduée du danger et des risques, telles que
celles développées dans l’ISO/TS 12901-2. L’état actuel des méthodes et des données de développement
des VLEP et des BEP pour les NOAA est décrit dans le présent document, ainsi qu’une évaluation des
méthodes utilisées pour développer les VLEP actuelles pour les NOAA. Les approches par catégories
pour déduire des BEP pour les NOAA à partir de données limitées sont également abordées, notamment
celles basées sur le mode d’action (MdA) biologique et les propriétés physicochimiques (PC). La base
du cadre décrit dans le présent document est le Bulletin de renseignement de situation Approaches
[16]
to Developing Occupational Exposure Limits or Bands for Engineered Nanomaterials du NIOSH
(Institut national des États-Unis pour la sécurité et la santé au travail). Le présent document tient
compte également d’autres rapports de l’état de la science, dont les conclusions de l’atelier «Strategies
for Setting Occupational Exposure Limits for Engineered Nanomaterials» qui s’est tenu les 10 et
[6]
11 septembre 2012 à Washington, DC, États-Unis et celles de la réunion d’experts du groupe de travail
sur les nanomatériaux manufacturés de l’OCDE sur la catégorisation des nanomatériaux manufacturés,
[17]
17-19 septembre 2014 .
Le présent document s’adresse principalement aux professionnels de la santé et de la sécurité au
travail des gouvernements, de l’industrie et du milieu universitaire, qui possèdent une expertise dans
le développement de VLEP ou de BEP sur la base des préconisations du présent document. De plus,
l’approche basée sur les preuves décrite dans le présent document peut être utile dans l’évaluation
et/ou la vérification des schémas actuels de gestion graduée des dangers et des risques afin d’identifier
les lacunes dans les données clés. La gestion graduée des risques exige des informations sur la catégorie
de danger et sur la catégorie d’exposition applicables. Des outils de gestion graduée des risques
correctement vérifiés seraient très utiles, car ces outils exigent moins d’expertise et de ressources
spécialisées (que pour une évaluation des risques exhaustive) et sont accessibles à un plus grand nombre
de personnes et de petites entreprises. Par conséquent, le présent document peut être considéré comme
complémentaire à l’ISO/TS 12901-2 sur la gestion graduée des risques des nanomatériaux, puisqu’il
décrit l’actuel état de l’art en matière de processus d’affectation de nanomatériaux à des bandes de
danger/BEP lorsque les preuves scientifiques ne suffisent pas à développer une VLEP individuelle.
vi © ISO 2016 – Tous droits réservés

Certaines des méthodes citées mènent à des résultats qui ne sont pas nécessairement cohérents et ceci
peut être dû aux biais de sélection de la méthode par les auteurs. Dans ces cas, les résultats divergents
augmentent également la difficulté d’utiliser les informations pour établir en toute confiance des
niveaux d’exposition et de bandes. La tentative d’identification des méthodes qui mènent à des résultats
à la fois corrects et cohérents ne fait pas partie du domaine d’application du présent document. Lorsque
les méthodes mènent à des résultats divergents, il est espéré que le présent rapport entraînera le
développement d’autres méthodes qui conduiront à des améliorations, et que ces améliorations
pourront servir de base à la définition de niveaux d’exposition et de bandes.
Les objectifs du présent document sont notamment les suivants:
a) décrire un cadre conforme à l’actuel état de l’art, basé sur des preuves, pour le développement de
VLEP ou de BEP pour les NOAA manufacturés; et
b) examiner les données actuellement disponibles et les autres approches et méthodes utilisées (p.
ex. substances de référence et niveaux d’exposition de référence) dans la prise de décision pour la
gestion du risque professionnel en ce qui concerne les NOAA.
Il est prévu que le présent document contribue au développement de méthodes normalisées d’évaluation
du danger et du risque et facilite l’évaluation systématique du risque potentiel pour la santé d’exposition
professionnelle aux NOAA.
RAPPORT TECHNIQUE ISO/TR 18637:2016(F)
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)
1 Domaine d’application
Le présent document 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.
2 Références normatives
Le présent document ne contient aucune référence normative.
3 Termes et définitions
Pour les besoins du présent document, les termes et définitions de l’ISO/TS 80004-2 ainsi que les
suivants, s’appliquent.
L’ISO et l’IEC tiennent à jour des bases de données terminologiques destinées à être utilisées en
normalisation, consultables aux adresses suivantes:
— IEC Electropedia: disponible à l'adresse http://www.electropedia.org/;
— ISO Online browsing platform: disponible à l'adresse http://www.iso.org/obp.
3.1
agglomérat
ensemble de particules faiblement ou moyennement liées, dont l’aire de la surface externe résultante
est similaire à la somme des aires de surface de chacun des composants
Note 1 à l'article: Les forces assurant la cohésion des agglomérats sont faibles, par exemple des forces de Van der
Waals ou des forces résultant d’un simple enchevêtrement physique.
Note 2 à l'article: Les agglomérats sont également appelés particules secondaires et les particules sources
initiales sont appelées particules primaires.
[SOURCE: ISO 26824:2013, 1.2]
3.2
agrégat
particule composée de particules fortement liées ou fusionnées, dont l’aire de la surface externe
résultante est significativement plus petite que la somme des aires de surface de chacun des composants
Note 1 à l'article: Les forces assurant la cohésion d’un agrégat sont puissantes, par exemple des liaisons
covalentes ou ioniques, ou des forces résultant d’un frittage ou d’un enchevêtrement physique complexe, ou sinon
d’anciennes particules primaires combinées.
Note 2 à l'article: Les agrégats sont également appelés particules secondaires et les particules sources initiales
sont appelées particules primaires.
[SOURCE: ISO/TS 80004-2:2015, 3.5]
3.3
matériau en masse
matériau de même composition chimique que les NOAA, à une échelle plus grande que l’échelle
nanométrique
3.4
exposition
contact avec un agent chimique, physique ou biologique par ingestion, inhalation ou contact avec la
peau ou les yeux
Note 1 à l'article: L’exposition peut être de courte durée (exposition aiguë), de durée intermédiaire ou de longue
durée (chronique).
3.5
danger pour la santé
source potentielle d’atteinte à la santé
[SOURCE: ISO 10993-17:2002, 3.7]
3.6
risque pour la santé
combinaison de la probabilité de voir un danger pour la santé se réaliser et du degré de gravité de celui-ci
[SOURCE: ISO 10993-17:2002, 3.8]
3.7
nanofibre
nano-objet ayant deux dimensions externes à l’échelle nanométrique et la troisième dimension externe
significativement plus grande
Note 1 à l'article: La plus grande des dimensions externes n’est pas nécessairement à l’échelle nanométrique.
Note 2 à l'article: Les termes nanofibrille et nanofilament peuvent également être utilisés.
Note 3 à l'article: Voir 3.9, Note 1 à l’article.
[SOURCE: ISO/TS 80004-2:2015, 4.5]
3.8
nano-objet
portion discrète de matériau dont une, deux ou les trois dimensions externes sont à l’échelle
nanométrique
Note 1 à l'article: Les deuxième et troisième dimensions externes sont orthogonales à la première dimension et
l’une par rapport à l’autre.
[SOURCE: ISO/TS 80004-1:2010, 2.2]
3.9
nanoparticule
nano-objet dont toutes les dimensions externes sont à l’échelle nanométrique et dont les longueurs du
plus grand et du plus petit axes ne diffèrent pas de façon significative
Note 1 à l'article: Si les dimensions diffèrent de façon significative (généralement d’un facteur supérieur à trois),
des termes tels que nanofibre ou nanoplaque peuvent être préférés au terme nanoparticule.
[SOURCE: ISO/TS 80004-2:2015, 4.4]
2 © ISO 2016 – Tous droits réservés

3.10
échelle nanométrique
échelle de longueur s’étendant d’approximativement de 1 nm à 100 nm
Note 1 à l'article: Les propriétés qui ne constituent pas des extrapolations par rapport à des dimensions plus
grandes sont principalement manifestes dans cette échelle de longueur.
[SOURCE: ISO/TS 80004-1:2010, 2.1]
3.11
particule
minuscule portion de matière avec des limites physiques bien définies
Note 1 à l'article: Une limite physique peut également être décrite sous la forme d’une interface.
Note 2 à l'article: Une particule peut se déplacer comme une unité.
Note 3 à l'article: Cette définition générale de «particule» s’applique aux nano-objets.
[SOURCE: ISO 26824:2013, 1.1]
3.12
solubilité
masse maximale d’un nanomatériau qui soit soluble dans un volume donné d’un solvant particulier
dans des conditions précises
Note 1 à l'article: La solubilité est exprimée en grammes par litre de solvant.
[SOURCE: ISO/TR 13014:2012, 2.27]
3.13
limite d’exposition professionnelle
concentration maximale d’agents contaminants en suspension dans l’air jugée acceptable, telle que
définie par l’autorité compétente
[SOURCE: ISO 16972:2010, 3.133]
3.14
bande d’exposition professionnelle
représentation quantitative de la bande de danger qui décrit le potentiel de danger d’un matériau ou
d’une classe de matériaux donné(e) dans l’air d’un lieu de travail
3.15
zone respiratoire
espace autour du visage d’un travailleur dans lequel celui-ci respire
Note 1 à l'article: [SOURCE: ISO 24095:2009, 3.1.2.1]
4 Symboles et abréviations
ACGIH American Conference of Governmental Industrial Hygienists (Conférence américaine des
hygiénistes industriels gouvernementaux)
AGS Ausschuss für Gefahrstoffe (Comité allemand sur les substances dangereuses)
AGW Arbeitsplatzgrenzwert (limite d’exposition au travail)
AIST Institut national japonais pour les sciences et technologies industrielles de pointe
BALF liquide de lavage broncho-alvéolaire (bronchoalveolar lavage fluid)
BAuA Bundesanstalt für Arbeitsschutz und Arbeitsmedizin (Institut fédéral allemand pour la
santé et la sécurité au travail)
BEP bande d’exposition professionnelle
BSI British Standards Institution (Institut de normalisation britannique)
CIRC Centre international de recherche sur le cancer
CMAR produit toxique cancérigène, mutagène, asthmagène ou toxique pour la reproduction
DFG Deutsche Forschungsgemeinschaft (Fondation allemande pour la recherche)
DMENO dose minimale avec effet nocif observé
DR dose de référence
DSENO dose sans effet nocif observé
EPA Agence américaine de protection de l’environnement
EQR évaluation quantitative du risque
EU-OSHA European Agency for Safety and Health at Work (Agence européenne pour la sécurité et
la santé au travail)
GBP particule granulaire biopersistante
GHS Globally harmonized system of classification and labelling of chemicals (Système mondial
harmonisé de classification et d’étiquetage des produits chimiques)
IEB indice d’exposition biologique
IFA Institut für Arbeitsschutz (Institut allemand pour la santé et la sécurité au travail)
JSOH Agence japonaise pour la santé professionnelle
LC50 concentration associée à 50 % de létalité
LDR estimation de dose de référence, limite de confiance inférieure 95 %
LEA limite d’exposition admissible
LECD limite d’exposition de courte durée
LEP limite d’exposition professionnelle
LER limite d’exposition recommandée
MAK Maximale Arbeitsplatzkonzentration (concentration maximale sur le lieu de travail)
MCP microscopie en contraste de phase
MdA mode d’action biologique
MOEL Ministère coréen de l’Emploi et du travail
MPTMPT moyenne pondérée dans le temps
MSHA United States Mine Safety et Health Administration (Administration de la santé et la
sécurité dans les mines)
4 © ISO 2016 – Tous droits réservés

MWCNT nanotube de carbone à parois multiples
NEMD niveau d’exposition minimale dérivé
NER niveau d’exposition de référence
NFC nanofibre de carbone
NIOSH United States National Institute for Occupational Safety and Health (Institut national des
États-Unis pour la sécurité et la santé au travail)
NOAA nano-objets et leurs agrégats et agglomérats y compris ceux de taille supérieure à 100 nm
NSED niveau sans effet dérivé
NTC nanotube de carbone
OCDE Organisation de coopération et de développement économiques
OMS Organisation mondiale de la santé
OSHA United States Occupational Safety and Health Administration (Administration fédérale
américaine de la santé et la sécurité au travail)
PC physicochimique
REACH Enregistrement, évaluation et autorisation des substances chimiques et restrictions
applicables à ces substances
SCENIHR Scientific Committee on Emerging and Newly Identified Health Risks (Comité scientifique
des risques sanitaires émergents et nouveaux)
SCOEL Scientific Committee on Occupational Exposure Limits (Comité scientifique sur les valeurs
limites d’exposition professionnelle)
SST santé et sécurité au travail
STOT-RE Toxicité pour un organe cible spécifique — exposition répétée
STOT-SE Toxicité pour un organe cible spécifique — exposition unique
SWCNT nanotube de carbone à paroi simple
TSCA Toxic Substances Control Act (loi sur le contrôle des substances toxiques)
UE Union européenne
UF ultrafin
VLEP valeur limite d’exposition professionnelle
VLEP (DL) valeur limite d’exposition professionnelle à durée limitée
VLI valeur limite indicative
VLS valeur limite de seuil
VNR nano-valeur de référence
WHS Work Health and Safety (santé et sécurité au travail)
5 Description des processus disponibles pour la définition des VLEP et des BEP
5.1 Considérations générales
L’exposition à des substances ou mélanges sur le lieu de travail peut se produire par inhalation,
absorption par la peau ou ingestion. La majorité des expositions se produisent par l’inhalation de
vapeurs, de poussières, de fumées ou de gaz. Pour certains produits chimiques, l’absorption par la peau
peut également représenter une source d’exposition importante.
La réponse du corps à l’exposition à des substances et mélanges dépend de la nature de la substance, des
effets qu’elle peut avoir sur la santé et de la quantité de substance ou de mélange absorbée par le corps.
Les individus possèdent de plus des capacités différentes de métabolisation des produits chimiques, ce
qui peut entraîner des variations très importantes des effets toxiques selon les personnes. L’étendue
selon laquelle une personne est exposée dépend principalement de la concentration de la substance
ou du mélange dans l’air et de la durée d’exposition et bien entendu, de l’efficacité des contrôles. Les
substances et les mélanges peuvent entraîner des effets aigus immédiats sur la santé ou il peut se passer
plusieurs jours avant que les effets sur le corps deviennent évidents.
Les valeurs limites d’exposition professionnelle sont destinées à prévenir les effets indésirables sur la
[18]
santé de «presque tous les travailleurs» , même en cas d’exposition quotidienne ou répétée sur toute
une vie de travail. Certaines VLEP sont basées uniquement sur des données relatives aux effets sur la
santé (p. ex. VLS de l’ACGIH) et d’autres VLEP incluent également des considérations sur la faisabilité
technique (p. ex. LER du NIOSH) ou la faisabilité économique (p. ex. LEA de l’OSHA) des mesures et du
contrôle des expositions.
Pour quelques substances, généralement les substances cancérigènes pour l’humain les plus puissantes,
probables et établies, il n’est aujourd’hui pas possible d’attribuer une limite d’exposition appropriée.
Pour ces substances, il convient de contrôler l’exposition au niveau le plus bas possible. La surveillance
biologique peut donner une indication plus fiable de l’exposition sur le lieu de travail pour ces
substances.
L’évaluation des dangers dus aux contaminants atmosphériques dans l’environnement de travail
constitue souvent une tâche complexe, qui prend en compte la variabilité potentiellement importante
de l’exposition sur le lieu de travail qui exige des stratégies sûres d’évaluation de l’exposition et
de l’hygiène professionnelle. Pour cette raison, il est essentiel que les personnes chargées de ces
évaluations soient des professionnels compétents et expérimentés, pleinement conscients de tous les
aspects traités dans le présent document et possédant les qualifications et l’expérience appropriées en
hygiène professionnelle.
NOTE Un professionnel compétent et expérimenté est une personne qui exécute correctement une tâche
spécifique. Cette personne utilise une combinaison de connaissances, de compétences et de comportements pour
améliorer sa performance. De façon plus générale, la compétence est l’état ou la qualité consistant à être qualifié
[3]
correctement ou de façon adéquate et à disposer de la capacité à remplir une fonction spécifique .
Il convient de ne pas utiliser les relations entre les diverses limites d’exposition comme mesure générale
de leur toxicité relative. La raison en est, entre autres, que les valeurs des différentes substances sont
souvent établies en relation avec des effets biologiques différents, comme l’irritation ou la toxicité
systémique. De même, il convient de ne pas utiliser les limites d’exposition comme base de l’évaluation
de la qualité de l’air d’une communauté ou d’expositions de longue durée qui n’ont pas lieu sur le lieu de
travail.
La plupart des substances utilisées dans l’industrie ne disposent pas de limites d’exposition assignées.
Cela n’implique pas que ces substances soient sûres ou non dangereuses. Dans de nombreux cas, les
informations sur les effets sur la santé de ces substances non classifiées ne sont pas suffisantes pour
permettre aux organismes règlementaires nationaux d’attribuer une limite d’exposition, même sous
forme de tentative. Dans d’autres cas, l’utilisation de la substance ne mène pas à des niveaux significatifs
de contaminants en suspension dans l’air, ou bien son utilisation est si restreinte qu’aucune limite
d’exposition n’est garantie.
6 © ISO 2016 – Tous droits réservés

Maintenir l’exposition à toute substance aussi faible que possible, que les informations actuelles
indiquent ou non qu’elle est dangereuse, constitue une bonne approche. Certaines substances
précédemment considérées comme comparativement sûres se sont ensuite révélées poser de sérieux
problèmes à long terme pour la santé.
Il existe trois types de limites d’exposition:
— limite d’exposition moyenne pondérée dans le temps (MPT);
— limite d’exposition de courte durée (LECD);
— limite de crête ou plafond.
Ces limites ainsi que d’autres aspects techniques de définition des VLEP sont décrits plus en détails
en A.1.2.
5.2 Description du processus basé sur la preuve
Les méthodes permettant de développer les VLEP dépendent des données disponibles. Schulte, et
[5]
al. décrivent trois scénarios généraux pour faire varier les quantités de données toxicologiques. Ce
cadre conceptuel a été affiné pour décrire les liens entre les bases de la preuve pour ces catégories
générales par le biais de substances de référence. Les substances de référence sont des matériaux bien
caractérisés (p. ex. des particules en suspension dans l’air ou des fibres), disposant de suffisamment
de données de dose-réponse d’études animales et/ou humaines pour développer des estimations
[19][20]
quantitatives du risque et des VLEP basées sur la santé (Figure 1). Les matériaux de référence
fournissent eux aussi une référence (p. ex. de contrôle positif ou négatif) dans les essais comparatifs de
toxicité de nouveaux NOAA qui disposent de données toxicologiques limitées mais ont des propriétés
[19][20][21]
physicochimiques ainsi qu’un mode d’action (MdA) biologique déduit similaires. Le présent
document est consacré aux expositions aux nanomatériaux en suspension dans l’air sur le lieu de travail,
puisque l’inhalation est la principale voie d’exposition à des substances potentiellement dangereuses,
dont les NOAA, sur le lieu de travail.
Comme représenté à la Figure 1, dans le premier cas, si les données de dose-réponse sont insuffisantes,
une VLEP pour un NOAA individuel peut être développée au moyen d’une évaluation quantitative des
risques (EQR). La définition du terme «suffisantes» est en dernier recours basée sur un jugement sur
les données disponibles et peut comprendre des évaluations de valeur probante, dont la disponibilité de
données adéquates pour une modélisation de dose de Référence [22], de dose sans effet nocif observé
(DSENO) ou de dose minimale avec effet nocif observé (DMENO) à partir d’études judicieusement menées.
Deuxièmement, si les données sont insuffisantes pour une EQR pour une substance spécifique, mais
que des informations adéquates sont disponibles pour une substance similaire dans la même catégorie
de mode d’action, une VLEP catégorielle peut être attribuée au moyen de méthodes qualitatives ou
quantitatives comprenant la modélisation en lecture croisée et de la bioactivité structurelle, avec
des comparaisons entre les NOAA et les substances de référence. Troisièmement, si les données sont
insuffisantes pour développer une VLEP spécifique à une substance ou catégorielle, alors des bandes
initiales (par défaut) de danger et de risque peuvent être établies en comparant les propriétés du NOAA
à celles de matériaux similaires dans des catégories plus larges. L’objectif de cette approche basée sur la
preuve est de faciliter la prise de décision concernant les stratégies de contrôle de l’exposition pour les
NOAA sur le lieu de travail, sur la base des meilleures évidences disponibles. Le cadre conceptuel permet
l’itération et la révision d’une BEP ou d’une VLEP lorsque des données supplémentaires deviennent
disponibles sur la base de critères normalisés pour les données et les méthodes. Aujourd’hui, il existe plus
d’exemples de VLEP développées pour des NOAA que de VLEP ou de BEP catégorielles pour des NOAA.
Les données disponibles pour développer les VLEP ou les BEP pour des NOAA peuvent inclure:
a) des données d’essais in vivo et in vitro de NOAA spécifiques (p. ex. du programme d’essais de l’OCDE,
des fabricants de NOAA et d’agences gouvernementales non règlementaires telles que le NIOSH et le
NTP aux États-Unis); et
b) des études toxicologiques ou épidémiologiques existantes d’effets sur les poumons de particules et
de fibres inhalées pour des analyses comparatives de toxicité.
Les bases de données générales de dangers chimiques (p. ex. celle utilisée dans la classification des
[23]
risques GHS ) sont également disponibles pour certains des matériaux parents ou en masse de
composition chimique similaire à celle du NOAA à utiliser dans l’attribution de la bande de danger/la
BEP et la gestion graduée des risques (voir p. ex. l’ISO/TS 12901-2). Le Tableau 1 récapitule le type de
données et de méthodes nécessaires pour développer des VLEP ou des BEP.
Figure 1 — Stratégie basée sur la preuve de développement de limites et de bandes de contrôle
de l’exposition pour les NOAA, basée sur le niveau de preuve
Tableau 1 — Données et méthodes nécessaires pour développer des limites ou des bandes
d’exposition
Valeur guide Niveau de preuve Données, outils et méthodes d’analyse
VLEP spécifique à la subs- Suffisantes Données de dose-réponse spécifiques à la substance
tance pour l’évaluation quantitative des risques; disponibilité
d’une méthode d’échantillonnage et analytique spéci-
fique à la substance
VLEP catégorielle Limitées (ciblées) Toxicité comparative, regroupement et catégorisation
pour estimer le danger ou le risque sur la base des
propriétés physicochimiques et des données de mode
d’action biologique
BEP Minimales ou inadé- Analogie; les catégories de danger et les options de
quates contrôle de l’exposition par défaut sont appliquées
5.3 VLEP spécifiques à la substance
Les VLEP spécifiques à une substance ne tiennent généralement pas compte de la taille des
nanoparticules, bien que certaines de ces VLEP spécifient bien les critères d’échantillonnage de taille
de parti
...