Evaluation of methods for assessing the release of nanomaterials from commercial, nanomaterial-containing polymer composites

This document reviews and evaluates the utility of available methods to assess material released from commercial polymer composites in support of product use and safety decisions, and describes what revised or additional methods are needed. The document is not focused on describing methods per se; rather the goal is to describe information that is appropriate for consideration in the selection of methods to support decision-making.

Évaluation des méthodes de détermination d'émission de nanomatériaux par des polymères composites commerciaux, contenant des nanomatériaux

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Publication Date
12-Jul-2021
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6060 - International Standard published
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13-Jul-2021
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TECHNICAL ISO/TR
REPORT 22293
First edition
2021-07
Evaluation of methods for assessing
the release of nanomaterials from
commercial, nanomaterial-containing
polymer composites
Évaluation des méthodes de détermination d'émission de
nanomatériaux par des polymères composites commerciaux,
contenant des nanomatériaux
Reference number
ISO/TR 22293:2021(E)
ISO 2021
---------------------- Page: 1 ----------------------
ISO/TR 22293:2021(E)
COPYRIGHT PROTECTED DOCUMENT
© ISO 2021

All rights reserved. Unless otherwise specified, or required in the context of its implementation, 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
CP 401 • Ch. de Blandonnet 8
CH-1214 Vernier, Geneva
Phone: +41 22 749 01 11
Email: copyright@iso.org
Website: www.iso.org
Published in Switzerland
ii © ISO 2021 – All rights reserved
---------------------- Page: 2 ----------------------
ISO/TR 22293:2021(E)
Contents Page

Foreword ..........................................................................................................................................................................................................................................v

Introduction ................................................................................................................................................................................................................................vi

1 Scope ................................................................................................................................................................................................................................. 1

2 Normative references ...................................................................................................................................................................................... 1

3 Terms and definitions ..................................................................................................................................................................................... 1

4 Abbreviations........................................................................................................................................................................................................... 3

5 Understanding the nano-enabled products ............................................................................................................................. 4

5.1 Pathway analysis for the supply chain ................................................................................................................................ 4

5.2 Matrix and MNM characteristics affecting rate and form of release......................................................... 8

5.2.1 General...................................................................................................................................................................................... 8

5.2.2 Consideration of the polymer used in the composite ...................................................................... 9

5.2.3 Polymer degradation .................................................................................................................................................10

5.2.4 Consideration of MNM used in the composite ....................................................................................10

5.2.5 Polymer nanocomposites ......................................................................................................................................11

5.2.6 Application areas and use phase (or lifecycle) processes .........................................................12

6 Factors affecting release measurement method selection ....................................................................................15

6.1 General ........................................................................................................................................................................................................15

6.2 Forms of release ..................................................................................................................................................................................16

6.3 Decision support framework to determine which transformations need

consideration with examples ...................................................................................................................................................21

7 Approaches to detecting and quantifying the released material associated with

added manufactured nanomaterials ............................................................................................................................................23

7.1 General ........................................................................................................................................................................................................23

7.2 Methods for sampling released material .......................................................................................................................23

7.2.1 General...................................................................................................................................................................................23

7.2.2 Sampling material released into air .............................................................................................................24

7.2.3 Sampling material released into water, solids, and biological fluids ...............................25

7.3 Methods for preparing samples of released material for subsequent analysis ...........................26

7.3.1 General...................................................................................................................................................................................26

7.3.2 Preparation and analysis of air samples ...................................................................................................26

7.3.3 Preparation and analysis of waters, solids and biological fluid samples .....................27

7.4 Measurement challenges .............................................................................................................................................................28

7.4.1 General...................................................................................................................................................................................28

7.4.2 Surface functionalization and transformations..................................................................................28

7.4.3 Sample collection artefacts ..................................................................................................................................29

7.4.4 Applicability of a measurement method for a given release media ..................................29

7.4.5 Sample preparation artefacts.............................................................................................................................29

7.4.6 Capability of a measurement method .........................................................................................................29

7.4.7 Representativeness of measurements .......................................................................................................30

7.4.8 Composition measurements ...............................................................................................................................30

7.4.9 Polymer stability ...........................................................................................................................................................30

7.4.10 Commercial practices ...............................................................................................................................................30

7.5 Considerations for detection, quantification, and determination of properties of

released materials .............................................................................................................................................................................31

7.6 Applicable measurement methods .....................................................................................................................................32

8 Identification of needs for standards, methods, instrumentation, decision

frameworks, and research .......................................................................................................................................................................32

8.1 General ........................................................................................................................................................................................................32

8.2 Potential improved/new methods ......................................................................................................................................32

8.3 Inter-laboratory studies ...............................................................................................................................................................33

8.4 Protocols and assays .......................................................................................................................................................................34

© ISO 2021 – All rights reserved iii
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ISO/TR 22293:2021(E)

8.5 Opportunities for standardization of methods ........................................................................................................34

8.6 Decision frameworks ......................................................................................................................................................................35

Annex A (informative) Example case studies............................................................................................................................................38

Bibliography .............................................................................................................................................................................................................................57

iv © ISO 2021 – All rights reserved
---------------------- Page: 4 ----------------------
ISO/TR 22293:2021(E)
Foreword

ISO (the International Organization for Standardization) is a worldwide federation of national standards

bodies (ISO member bodies). The work of preparing International Standards is normally carried out

through ISO technical committees. Each member body interested in a subject for which a technical

committee has been established has the right to be represented on that committee. International

organizations, governmental and non-governmental, in liaison with ISO, also take part in the work.

ISO collaborates closely with the International Electrotechnical Commission (IEC) on all matters of

electrotechnical standardization.

The procedures used to develop this document and those intended for its further maintenance are

described in the ISO/IEC Directives, Part 1. In particular, the different approval criteria needed for the

different types of ISO documents should be noted. This document was drafted in accordance with the

editorial rules of the ISO/IEC Directives, Part 2 (see www .iso .org/ directives).

Attention is drawn to the possibility that some of the elements of this document may be the subject of

patent rights. ISO shall not be held responsible for identifying any or all such patent rights. Details of

any patent rights identified during the development of the document will be in the Introduction and/or

on the ISO list of patent declarations received (see www .iso .org/ patents).

Any trade name used in this document is information given for the convenience of users and does not

constitute an endorsement.

For an explanation of the voluntary nature of standards, 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 www .iso .org/

iso/ foreword .html.
This document was prepared by Technical Committee ISO/TC 229, Nanotechnologies.

Any feedback or questions on this document should be directed to the user’s national standards body. A

complete listing of these bodies can be found at www .iso .org/ members .html.
© ISO 2021 – All rights reserved v
---------------------- Page: 5 ----------------------
ISO/TR 22293:2021(E)
Introduction
0.1 General

The use of manufactured nanomaterials (MNM) in consumer products and applications is growing as

manufacturers exploit the unique properties of nanomaterials. MNMs are an increasingly common

feature of a growing variety of commercial applications and consumer products — from computer chips

to golf clubs. So too are concerns over what is or can be released from products containing MNMs, and

the risk and potential impacts of exposure to such releases. These unique properties offer significant

commercial value, enabling the manufacture of products that that offer novel characteristics. The MNM

might be embedded in solids, might be suspended in fluid, or might be bound to the surface of solid

products. An understanding of what is released from products containing MNMs is critical to planning

and managing safe development and use of those products.

This document aims to contribute to that understanding by providing a guide to the information to

be taken into account in determining the methods for identifying and evaluating releases of MNMs

from matrices; providing a framework for understanding how these methods and the information they

produce can support decision-making; and identifying opportunities for developing standards in this

area.

This document provides practical support for decisions related to product development and use through

early consideration of the potential for release of MNM and through focus on realistic use scenarios

where exposures to the released MNM might occur.
The intended users of this document would include:

— those planning to develop or adapt technical specifications for MNM use in commercial products;

— risk managers, product developers, exposure measurement practitioners or other stakeholders

seeking guidance on the availability and utility of methods to measure releases that could occur

from uses of specific MNMs in composites;

— methods and instrumentation developers seeking to identify needs of the risk management

community;

— those planning basic and applied research programs for measurement and modelling to support

decisions around sustainably safe uses of MNMs.

The structured review of the information regarding the selection of MNM measurement methods

provided in this document is needed because technologies to produce MNMs, their uses, and MNM

measurement methods are often developing at the same time, and the development of measurement

methods can in some cases lag behind product development needs. Furthermore, the need to measure

particular characteristics of the released MNM might also evolve as greater understanding of what

might cause toxicity for a particular kind of MNM is gained. This relationship between emerging

measurement methods and emerging information about toxicity makes a structured approach to review

of measurement needs even more important, so that data are assembled to support decisions using the

most up-to-date and fit-to-purpose measurement methods. Finally, the selection process for choosing

a particular MNM-composite for a product should include the consideration of whether the available

measurement methods are feasible for the evaluating the conditions of use of that MNM-composite.

This consideration is needed because many methods available for research or for controlled conditions

in industrial hygiene settings are not useful for realistic measurement needs where consumers might

be exposed. In some cases, those methods are too difficult to conduct outside of the laboratory, and in

other cases the methods are too labour-intensive to be feasible for routine decision support.

The development of the decision-making framework presented in this document is based in large part

on initial analyses that focused on releases from polyamide or epoxy polymers to which multi-wall

carbon nanotubes (MWCNT) have been added. Nonetheless, the framework can be used to inform the

selection of methods for identifying and evaluating the releases for a wide range of MNMs and types of

matrices, as illustrated by the case studies in Annex A. The case studies have been chosen because of

the availability of information and methods relevant for actual MNM-polymer composite uses.

vi © ISO 2021 – All rights reserved
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ISO/TR 22293:2021(E)

Release from polymer nanocomposites can occur through processes such as physical, chemical, or

thermal degradation of a polymer matrix, resulting in particles that might include a mixture of free

MNM, free polymer, and matrix-bound MNM. This document focuses on the first release to human

exposure or to an effluent pathway. While acknowledging that subsequent MNM fate and transport

could follow from this initial release, the primary concern of this document is whether and where

release of MNMs can occur in the context of consumer or commercial use, and the need to monitor

likelihood of human exposure potential. Although other stages of the lifecycle of products containing

MNMs are discussed briefly to provide context, subsequent fate and transport events are not addressed

in detail.

The ultimate goal is to use the report structure of this document as a foundation for addressing releases

of other MNMs from other matrices in subsequent versions of the document.
0.2 Decision-Making Framework
0.2.1 General

In developing the decision-making framework set out in this document two key concepts that have

proven useful in addressing the relevant risk management issues in support of decision-making have

[1]

been applied. The first is “problem formulation” . This describes the purpose and context of the

analysis, and the nature of the decision that the analysis aims to support. By making it clear the analysis

is being conducted to support a specific decision, this approach helps to ensure the analysis remains

focused on methods that have practical application in making that decision. The second key concept

is “fit for purpose.” In other words, the nature of the analytical approach used should be sufficient for

and appropriate to addressing the specific risk management decision. This includes assuring that the

depth of analysis - including consideration of the sources and potential magnitude of uncertainty – is

consistent with the information needed to support the decision. In the context of this document, this

means that feasibility is an important consideration in the choice of analytical methods.

0.2.2 Application of concepts

In applying these concepts to the selection of methods for identifying and evaluating releases of

MNMs from matrices, the problem formulation would include an evaluation of the potential for human

exposure to the component of the nano-enabled product (NEP) that contains the MNM and the potential

for MNM release from that component.

To evaluate the potential for human exposure, an understanding of the product design and the potential

use scenarios is required. If, for example, the component containing the MNM is fully encased within a

consumer product, or is part of a machine where it is accessible only during maintenance, there are

limited opportunities for human exposure as part of the release event. Description of potential use

scenarios is also critical for understanding the potential nature of human exposure (e.g. direct dermal

contact vs. inhalation of released MNM), as well as relevant conditions of potential wear and aging (e.g.

potential and nature of abrasion, temperature, presence or absence of water and UV light).

Together, these elements of the problem formulation can aid in determining which potential release

scenarios need to be tested, as well as the nature of the analytical methods needed and, thus, aid in

determining whether it is feasible to evaluate the risk of a given choice of product composition without

substantial investment in analytical methods development.
0.2.3 Tiered approach

In some situations, a tiered approach — such as those described in Clause 8 — can be useful. For

example, if release outside of a confined structure is not expected (e.g. if the MNM is contained within

a phone, and release would not result in consumer exposure), an analytical method that simply detects

the MNM could be sufficient. In other cases, a qualitative description might be useful to predict the

potential for further interactions with other materials, and ultimately the fate and transport of the

MNM. Such information could be used, for example, in deciding between alternative designs or products

0.2.4 Quantitative risk assessment presents challenges
© ISO 2021 – All rights reserved vii
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ISO/TR 22293:2021(E)

Finally, in some cases it could be necessary to quantitatively evaluate the MNM release in order to feed

into a quantitative risk assessment. In such cases, it is important to ensure that exposure measurements

are made in a way that facilitates integration with hazard data to evaluate risk. Such integration

includes evaluating the MNM characteristics with regard to key determinants of toxicity (e.g. degree of

aggregation and functionalization), and reporting exposure in relevant dose units. Currently completing

an evaluation of this kind presents a significant challenge, as the key determinants of toxicity and

appropriate dose units are still being identified in many situations.
0.2.5 Data requirements

As described in this document, key data needs to support a decision related to product development

and use include:
— a description of the NEP and where in the product the MNM is found;

— a description of common use scenarios, including frequency of use and relevant populations;

— a description of potential degradation mechanisms that can lead to release under the use scenario(s)

of interest;
— a description of the nanomaterial;

— a description of the composite matrix and its resistance to degradation under the use scenario(s) of

interest.

Based on this information, the assessor can determine the potential for release (including the release

rate) and the likely media into which the release might occur. These parameters in turn inform the

nature of sampling and analytic methods that might be needed.
0.3 Document structure and use

After a brief discussion of how the topic of this document relates to Lifecycle analysis, the document

addresses the structure of the polymer and the embedded MNM, and how those structures inform

measurement methods needs through their effect on the release rate and the form of the release

(Clause 5). Clause 6 describes how the relative resilience of the polymer matrix and the embedded MNM

inform measurement methods needs through their effect on the nature of the resulting release and

proposes a tiered (stepwise) decision framework for deciding if or which transformations at the release

point need to be considered. Worked examples applying the decision framework outlined in 6.3 are

presented in Annex A. Clause 7 addresses methods for measuring and describing the characteristics of

the released material, including sampling methods in various media, methods for sample preparation

and analysis, and measurement challenges. Clause 8 addresses remaining gaps and data needs, and

briefly reviews several available decision frameworks to support risk managers in determining the

information and sampling methods needed to support product design and development decisions.

It is anticipated that the information presented in this document will find application in assisting

manufacturers and regulatory agencies to more clearly identify products and scenarios with low

consumer exposure potential (e.g. where the MNM is part of a component that is fully encased) and

those products and scenarios with higher exposure potential (e.g. the MNM is in continuous contact

with human skin or is used under conditions subject to severe weathering). This document is also

intended to aid in evaluating — at the product design stage — how variation in adducts, coatings, or

MNM composition would affect MNM release rates and measurement needs.
viii © ISO 2021 – All rights reserved
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TECHNICAL REPORT ISO/TR 22293:2021(E)
Evaluation of methods for assessing the release of
nanomaterials from commercial, nanomaterial-containing
polymer composites
1 Scope

This document reviews and evaluates the utility of available methods to assess material released from

commercial polymer composites in support of product use and safety decisions, and describes what

revised or additional methods are needed. The document is not focused on describing methods per

se; rather the goal is to describe information that is appropriate for consideration in the selection of

methods to support decision-making.
2 Normative references

The following documents are referred to in the text in such a way that some or all of their content

constitutes requirements of this document. For dated references, only the edition cited applies. For

undated references, the latest edition of the referenced document (including any amendments) applies.

ISO/TS 80004 (all parts), Nanotechnologies — Vocabulary
3 Terms and definitions

For the purposes of this document, the terms and definitions given in ISO/TS 80004 (all parts) and the

following apply.

ISO and IEC maintain terminological databases for use in standardization at the following addresses:

— ISO Online browsing platform: available at https:// www .iso .org/ obp
— IEC Electropedia: available at https:// www .electropedia .org/
3.1
manufactured nanomaterial
MNM
nanomaterial intentionally produced to have selected properties or composition
[SOURCE: ISO/TS 80004-1:2015, 2.9]
3.2
nanocomposite

solid comprising a mixture of two or more phase-separated materials, one or more being nanophase

Note 1 to entry: Gaseous nanophases are excluded [they are covered by nanoporous material].

Note 2 to entry: Materials with nanoscale phases formed by precipitation alone are not considered to be

nanocomposite materials.
[SOURCE: ISO/TS 80004-4:2011, 3.2]
© ISO 2021 – All rights reserved 1
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ISO/TR 22293:2021(E)
3.3
carbon nanotube
CNT
nanotube composed of carbon

Note 1 to entry: Carbon nanotubes usually consist of curved graphene layers, including single-wall carbon

nanotubes and multiwall carbon nanotubes.
[SOURCE: ISO/TS 80004-3:2010, 4.3]
3.4
multi-wall carbon nanotube
MWCNT

carbon nanotube composed of nested, concentric or near-concentric graphene sheets with interlayer

distance similar to those of graphite

Note 1 to entry: The structure is normally considered to be many single-wall carbon nanotubes nesting each

other, and would be cylindrical for small diameters but tends to have a polygonal cross-section as the diameter

increases.
[SOURCE: ISO/TS 80004-3:2010, 4.6]
3.5
lifecycle

consecutive and interlinked stages of a product system, from raw material acquisition or generation

from natural resources to final disposal

[SOURCE: ISO 14044:2006, 3.1, modified — the term has been modified from "life cycle" to "lifecycle".]

3.6
nano-enabled
exhibiting function or performance only possible with nanotechnology
[SOURCE: ISO/TS 80004-1:2015, 2.15]
3.7
single wall carbon nanotube
SWCNT
carbon nanotube consisting of a single cylindrical graphene layer

Note 1 to entry: The structure can be visualized as a graphene sheet rolled into a cylindrical honeycomb

structure.
[SOURCE: ISO/TS 80004-3:2010, 4.4]
3.8
nano-enhanced
exhibiting function or performance intensified or improved by nanotechnology
[SOURCE: ISO/TS 80004-1:2015, 2.16]
3.9
nanoscale
length range approximately from 1 nm to 100 nm

Note 1 to entry: Properties that are not extrapolations from larger sizes are predominantly exhibited in this

length range.
[SOURCE: ISO/TS 80004-1:2015, 2.1]
2 © ISO 2021 – All rights reserved
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ISO/TR 22293:2021(E)
3.10
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 an agglomerate 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]
3.11
graphene oxide

chemically modified graphene prepared by the oxidation of graphite causing extensive oxidative

modification of the basal plane

[SOURCE: ISO/TS 80004-13:2017, 3.1.2.13, modified — "and exfoliation" has been deleted.]

3.12
additive
substance added to polymers to improve or modify one or more particles

Note 1 to entry: In a narrow sense, the term additive includes only ingredients added in small amounts; in

...

TECHNICAL ISO/TR
REPORT 22293
First edition
Evaluation of methods for assessing
the release of nanomaterials from
commercial, nanomaterial-containing
polymer composites
Évaluation des méthodes de détermination d'émission de
nanomatériaux par des polymères composites commerciaux,
contenant des nanomatériaux
PROOF/ÉPREUVE
Reference number
ISO/TR 22293:2021(E)
ISO 2021
---------------------- Page: 1 ----------------------
ISO/TR 22293:2021(E)
COPYRIGHT PROTECTED DOCUMENT
© ISO 2021

All rights reserved. Unless otherwise specified, or required in the context of its implementation, 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
CP 401 • Ch. de Blandonnet 8
CH-1214 Vernier, Geneva
Phone: +41 22 749 01 11
Email: copyright@iso.org
Website: www.iso.org
Published in Switzerland
ii PROOF/ÉPREUVE © ISO 2021 – All rights reserved
---------------------- Page: 2 ----------------------
ISO/TR 22293:2021(E)
Contents Page

Foreword ..........................................................................................................................................................................................................................................v

Introduction ................................................................................................................................................................................................................................vi

1 Scope ................................................................................................................................................................................................................................. 1

2 Normative references ...................................................................................................................................................................................... 1

3 Terms and definitions ..................................................................................................................................................................................... 1

4 Abbreviations........................................................................................................................................................................................................... 3

5 Understanding the nano-enabled products ............................................................................................................................. 4

5.1 Pathway analysis for the supply chain ................................................................................................................................ 4

5.2 Matrix and MNM characteristics affecting rate and form of release......................................................... 8

5.2.1 General...................................................................................................................................................................................... 8

5.2.2 Consideration of the polymer used in the composite ...................................................................... 9

5.2.3 Polymer degradation .................................................................................................................................................10

5.2.4 Consideration of MNM used in the composite ....................................................................................10

5.2.5 Polymer nanocomposites ......................................................................................................................................11

5.2.6 Application areas and use phase (or lifecycle) processes .........................................................12

6 Factors affecting release measurement method selection ....................................................................................15

6.1 General ........................................................................................................................................................................................................15

6.2 Forms of release ..................................................................................................................................................................................16

6.3 Decision support framework to determine which transformations need

consideration with examples ...................................................................................................................................................21

7 Approaches to detecting and quantifying the released material associated with

added manufactured nanomaterials ............................................................................................................................................23

7.1 General ........................................................................................................................................................................................................23

7.2 Methods for sampling released material .......................................................................................................................23

7.2.1 General...................................................................................................................................................................................23

7.2.2 Sampling material released into air .............................................................................................................24

7.2.3 Sampling material released into water, solids, and biological fluids ...............................25

7.3 Methods for preparing samples of released material for subsequent analysis ...........................26

7.3.1 General...................................................................................................................................................................................26

7.3.2 Preparation and analysis of air samples ...................................................................................................26

7.3.3 Preparation and analysis of waters, solids and biological fluid samples .....................27

7.4 Measurement challenges .............................................................................................................................................................28

7.4.1 General...................................................................................................................................................................................28

7.4.2 Surface functionalization and transformations..................................................................................28

7.4.3 Sample collection artefacts ..................................................................................................................................29

7.4.4 Applicability of a measurement method for a given release media ..................................29

7.4.5 Sample preparation artefacts.............................................................................................................................29

7.4.6 Capability of a measurement method .........................................................................................................29

7.4.7 Representativeness of measurements .......................................................................................................30

7.4.8 Composition measurements ...............................................................................................................................30

7.4.9 Polymer stability ...........................................................................................................................................................30

7.4.10 Commercial practices ...............................................................................................................................................30

7.5 Considerations for detection, quantification, and determination of properties of

released materials .............................................................................................................................................................................31

7.6 Applicable measurement methods .....................................................................................................................................32

8 Identification of needs for standards, methods, instrumentation, decision

frameworks, and research .......................................................................................................................................................................32

8.1 General ........................................................................................................................................................................................................32

8.2 Potential improved/new methods ......................................................................................................................................32

8.3 Inter-laboratory studies ...............................................................................................................................................................33

8.4 Protocols and assays .......................................................................................................................................................................34

© ISO 2021 – All rights reserved PROOF/ÉPREUVE iii
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ISO/TR 22293:2021(E)

8.5 Opportunities for standardization of methods ........................................................................................................34

8.6 Decision frameworks ......................................................................................................................................................................35

Annex A (informative) Example case studies............................................................................................................................................38

Bibliography .............................................................................................................................................................................................................................57

iv PROOF/ÉPREUVE © ISO 2021 – All rights reserved
---------------------- Page: 4 ----------------------
ISO/TR 22293:2021(E)
Foreword

ISO (the International Organization for Standardization) is a worldwide federation of national standards

bodies (ISO member bodies). The work of preparing International Standards is normally carried out

through ISO technical committees. Each member body interested in a subject for which a technical

committee has been established has the right to be represented on that committee. International

organizations, governmental and non-governmental, in liaison with ISO, also take part in the work.

ISO collaborates closely with the International Electrotechnical Commission (IEC) on all matters of

electrotechnical standardization.

The procedures used to develop this document and those intended for its further maintenance are

described in the ISO/IEC Directives, Part 1. In particular, the different approval criteria needed for the

different types of ISO documents should be noted. This document was drafted in accordance with the

editorial rules of the ISO/IEC Directives, Part 2 (see www .iso .org/ directives).

Attention is drawn to the possibility that some of the elements of this document may be the subject of

patent rights. ISO shall not be held responsible for identifying any or all such patent rights. Details of

any patent rights identified during the development of the document will be in the Introduction and/or

on the ISO list of patent declarations received (see www .iso .org/ patents).

Any trade name used in this document is information given for the convenience of users and does not

constitute an endorsement.

For an explanation of the voluntary nature of standards, 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 www .iso .org/

iso/ foreword .html.
This document was prepared by Technical Committee ISO/TC 229, Nanotechnologies.

Any feedback or questions on this document should be directed to the user’s national standards body. A

complete listing of these bodies can be found at www .iso .org/ members .html.
© ISO 2021 – All rights reserved PROOF/ÉPREUVE v
---------------------- Page: 5 ----------------------
ISO/TR 22293:2021(E)
Introduction
0.1 General

The use of manufactured nanomaterials (MNM) in consumer products and applications is growing as

manufacturers exploit the unique properties of nanomaterials. MNMs are an increasingly common

feature of a growing variety of commercial applications and consumer products — from computer chips

to golf clubs. So too are concerns over what is or can be released from products containing MNMs, and

the risk and potential impacts of exposure to such releases. These unique properties offer significant

commercial value, enabling the manufacture of products that that offer novel characteristics. The MNM

might be embedded in solids, might be suspended in fluid, or might be bound to the surface of solid

products. An understanding of what is released from products containing MNMs is critical to planning

and managing safe development and use of those products.

This document aims to contribute to that understanding by providing a guide to the information to

be taken into account in determining the methods for identifying and evaluating releases of MNMs

from matrices; providing a framework for understanding how these methods and the information they

produce can support decision-making; and identifying opportunities for developing standards in this

area.

This document provides practical support for decisions related to product development and use through

early consideration of the potential for release of MNM and through focus on realistic use scenarios

where exposures to the released MNM might occur.
The intended users of this document would include:

— those planning to develop or adapt technical specifications for MNM use in commercial products;

— risk managers, product developers, exposure measurement practitioners or other stakeholders

seeking guidance on the availability and utility of methods to measure releases that could occur

from uses of specific MNMs in composites;

— methods and instrumentation developers seeking to identify needs of the risk management

community;

— those planning basic and applied research programs for measurement and modelling to support

decisions around sustainably safe uses of MNMs.

The structured review of the information regarding the selection of MNM measurement methods

provided in this document is needed because technologies to produce MNMs, their uses, and MNM

measurement methods are often developing at the same time, and the development of measurement

methods can in some cases lag behind product development needs. Furthermore, the need to measure

particular characteristics of the released MNM might also evolve as greater understanding of what

might cause toxicity for a particular kind of MNM is gained. This relationship between emerging

measurement methods and emerging information about toxicity makes a structured approach to review

of measurement needs even more important, so that data are assembled to support decisions using the

most up-to-date and fit-to-purpose measurement methods. Finally, the selection process for choosing

a particular MNM-composite for a product should include the consideration of whether the available

measurement methods are feasible for the evaluating the conditions of use of that MNM-composite.

This consideration is needed because many methods available for research or for controlled conditions

in industrial hygiene settings are not useful for realistic measurement needs where consumers might

be exposed. In some cases, those methods are too difficult to conduct outside of the laboratory, and in

other cases the methods are too labour-intensive to be feasible for routine decision support.

The development of the decision-making framework presented in this document is based in large part

on initial analyses that focused on releases from polyamide or epoxy polymers to which multi-wall

carbon nanotubes (MWCNT) have been added. Nonetheless, the framework can be used to inform the

selection of methods for identifying and evaluating the releases for a wide range of MNMs and types of

matrices, as illustrated by the case studies in Annex A. The case studies have been chosen because of

the availability of information and methods relevant for actual MNM-polymer composite uses.

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Release from polymer nanocomposites can occur through processes such as physical, chemical, or

thermal degradation of a polymer matrix, resulting in particles that might include a mixture of free

MNM, free polymer, and matrix-bound MNM. This document focuses on the first release to human

exposure or to an effluent pathway. While acknowledging that subsequent MNM fate and transport

could follow from this initial release, the primary concern of this document is whether and where

release of MNMs can occur in the context of consumer or commercial use, and the need to monitor

likelihood of human exposure potential. Although other stages of the lifecycle of products containing

MNMs are discussed briefly to provide context, subsequent fate and transport events are not addressed

in detail.

The ultimate goal is to use the report structure of this document as a foundation for addressing releases

of other MNMs from other matrices in subsequent versions of the document.
0.2 Decision-Making Framework
0.2.1 General

In developing the decision-making framework set out in this document two key concepts that have

proven useful in addressing the relevant risk management issues in support of decision-making have

[1]

been applied. The first is “problem formulation” . This describes the purpose and context of the

analysis, and the nature of the decision that the analysis aims to support. By making it clear the analysis

is being conducted to support a specific decision, this approach helps to ensure the analysis remains

focused on methods that have practical application in making that decision. The second key concept

is “fit for purpose.” In other words, the nature of the analytical approach used should be sufficient for

and appropriate to addressing the specific risk management decision. This includes assuring that the

depth of analysis - including consideration of the sources and potential magnitude of uncertainty – is

consistent with the information needed to support the decision. In the context of this document, this

means that feasibility is an important consideration in the choice of analytical methods.

0.2.2 Application of concepts

In applying these concepts to the selection of methods for identifying and evaluating releases of

MNMs from matrices, the problem formulation would include an evaluation of the potential for human

exposure to the component of the nano-enabled product (NEP) that contains the MNM and the potential

for MNM release from that component.

To evaluate the potential for human exposure, an understanding of the product design and the potential

use scenarios is required. If, for example, the component containing the MNM is fully encased within a

consumer product, or is part of a machine where it is accessible only during maintenance, there are

limited opportunities for human exposure as part of the release event. Description of potential use

scenarios is also critical for understanding the potential nature of human exposure (e.g. direct dermal

contact vs. inhalation of released MNM), as well as relevant conditions of potential wear and aging (e.g.

potential and nature of abrasion, temperature, presence or absence of water and UV light).

Together, these elements of the problem formulation can aid in determining which potential release

scenarios need to be tested, as well as the nature of the analytical methods needed and, thus, aid in

determining whether it is feasible to evaluate the risk of a given choice of product composition without

substantial investment in analytical methods development.
0.2.3 Tiered approach

In some situations, a tiered approach — such as those described in Clause 8 — can be useful. For

example, if release outside of a confined structure is not expected (e.g. if the MNM is contained within

a phone, and release would not result in consumer exposure), an analytical method that simply detects

the MNM could be sufficient. In other cases, a qualitative description might be useful to predict the

potential for further interactions with other materials, and ultimately the fate and transport of the

MNM. Such information could be used, for example, in deciding between alternative designs or products

0.2.4 Quantitative risk assessment presents challenges
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Finally, in some cases it could be necessary to quantitatively evaluate the MNM release in order to feed

into a quantitative risk assessment. In such cases, it is important to ensure that exposure measurements

are made in a way that facilitates integration with hazard data to evaluate risk. Such integration

includes evaluating the MNM characteristics with regard to key determinants of toxicity (e.g. degree of

aggregation and functionalization), and reporting exposure in relevant dose units. Currently completing

an evaluation of this kind presents a significant challenge, as the key determinants of toxicity and

appropriate dose units are still being identified in many situations.
0.2.5 Data requirements

As described in this document, key data needs to support a decision related to product development

and use include:
— a description of the NEP and where in the product the MNM is found;

— a description of common use scenarios, including frequency of use and relevant populations;

— a description of potential degradation mechanisms that can lead to release under the use scenario(s)

of interest;
— a description of the nanomaterial;

— a description of the composite matrix and its resistance to degradation under the use scenario(s) of

interest.

Based on this information, the assessor can determine the potential for release (including the release

rate) and the likely media into which the release might occur. These parameters in turn inform the

nature of sampling and analytic methods that might be needed.
0.3 Document structure and use

After a brief discussion of how the topic of this document relates to Lifecycle analysis, the document

addresses the structure of the polymer and the embedded MNM, and how those structures inform

measurement methods needs through their effect on the release rate and the form of the release

(Clause 5). Clause 6 describes how the relative resilience of the polymer matrix and the embedded MNM

inform measurement methods needs through their effect on the nature of the resulting release and

proposes a tiered (stepwise) decision framework for deciding if or which transformations at the release

point need to be considered. Worked examples applying the decision framework outlined in 6.3 are

presented in Annex A. Clause 7 addresses methods for measuring and describing the characteristics of

the released material, including sampling methods in various media, methods for sample preparation

and analysis, and measurement challenges. Clause 8 addresses remaining gaps and data needs, and

briefly reviews several available decision frameworks to support risk managers in determining the

information and sampling methods needed to support product design and development decisions.

It is anticipated that the information presented in this document will find application in assisting

manufacturers and regulatory agencies to more clearly identify products and scenarios with low

consumer exposure potential (e.g. where the MNM is part of a component that is fully encased) and

those products and scenarios with higher exposure potential (e.g. the MNM is in continuous contact

with human skin or is used under conditions subject to severe weathering). This document is also

intended to aid in evaluating — at the product design stage — how variation in adducts, coatings, or

MNM composition would affect MNM release rates and measurement needs.
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TECHNICAL REPORT ISO/TR 22293:2021(E)
Evaluation of methods for assessing the release of
nanomaterials from commercial, nanomaterial-containing
polymer composites
1 Scope

This document reviews and evaluates the utility of available methods to assess material released from

commercial polymer composites in support of product use and safety decisions, and describes what

revised or additional methods are needed. The document is not focused on describing methods per

se; rather the goal is to describe information that is appropriate for consideration in the selection of

methods to support decision-making.
2 Normative references

The following documents are referred to in the text in such a way that some or all of their content

constitutes requirements of this document. For dated references, only the edition cited applies. For

undated references, the latest edition of the referenced document (including any amendments) applies.

ISO/TS 80004 (all parts), Nanotechnologies — Vocabulary
3 Terms and definitions

For the purposes of this document, the terms and definitions given in ISO/TS 80004 (all parts) and the

following apply.

ISO and IEC maintain terminological databases for use in standardization at the following addresses:

— ISO Online browsing platform: available at https:// www .iso .org/ obp
— IEC Electropedia: available at http:// www .electropedia .org/
3.1
manufactured nanomaterial
MNM
nanomaterial intentionally produced to have selected properties or composition
[SOURCE: ISO/TS 80004-1:2015, 2.9]
3.2
nanocomposite

solid comprising a mixture of two or more phase-separated materials, one or more being nanophase

Note 1 to entry: Gaseous nanophases are excluded [they are covered by nanoporous material].

Note 2 to entry: Materials with nanoscale phases formed by precipitation alone are not considered to be

nanocomposite materials.
[SOURCE: ISO/TS 80004-4:2011, 3.2]
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3.3
carbon nanotube
CNT
nanotube composed of carbon

Note 1 to entry: Carbon nanotubes usually consist of curved graphene layers, including single-wall carbon

nanotubes and multiwall carbon nanotubes.
[SOURCE: ISO/TS 80004-3:2010, 4.3]
3.4
multi-wall carbon nanotube
MWCNT

carbon nanotube composed of nested, concentric or near-concentric graphene sheets with interlayer

distance similar to those of graphite

Note 1 to entry: The structure is normally considered to be many single-wall carbon nanotubes nesting each

other, and would be cylindrical for small diameters but tends to have a polygonal cross-section as the diameter

increases.
[SOURCE: ISO/TS 80004-3:2010, 4.6]
3.5
lifecycle

consecutive and interlinked stages of a product system, from raw material acquisition or generation

from natural resources to final disposal

[SOURCE: ISO 14044:2006, 3.1, modified — the term has been modified from "life cycle" to "lifecycle".]

3.6
nano-enabled
exhibiting function or performance only possible with nanotechnology
[SOURCE: ISO/TS 80004-1:2015, 2.15]
3.7
single wall carbon nanotube
SWCNT
carbon nanotube consisting of a single cylindrical graphene layer

Note 1 to entry: The structure can be visualized as a graphene sheet rolled into a cylindrical honeycomb

structure.
[SOURCE: ISO/TS 80004-3:2010, 4.4]
3.8
nano-enhanced
exhibiting function or performance intensified or improved by nanotechnology
[SOURCE: ISO/TS 80004-1:2015, 2.16]
3.9
nanoscale
length range approximately from 1 nm to 100 nm

Note 1 to entry: Properties that are not extrapolations from larger sizes are predominantly exhibited in this

length range.
[SOURCE: ISO/TS 80004-1:2015, 2.1]
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3.10
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 an agglomerate 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]
3.11
graphene oxide

chemically modified graphene prepared by the oxidation of graphite causing extensive oxidative

modification of the basal plane

[SOURCE: ISO/TS 80004-13:2017, 3.1.2.13, modified — "and exfoliation" has been deleted.]

3.12
additive
substance added to polymers to improve or modify one or
...

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