ISO/TR 23463:2022

TECHNICAL ISO/TR
REPORT 23463
First edition
2022-05
Nanotechnologies — Characterization
of carbon nanotube and carbon
nanofibre aerosols to be used in
inhalation toxicity tests
Nanotechnologies — Caractérisation des aérosols de nanotubes
de carbone et de nanofibres de carbone à utiliser dans les tests de
toxicité par inhalation
Reference number
© ISO 2022
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ii
Contents Page
Foreword .iv
Introduction .v
1 Scope . 1
2 Normative references . 1
3 Terms and definitions . 1
4 Abbreviated terms . 8
5 Considerations in CNT and CNF inhalation studies . 8
5.1 General . 8
5.2 Workplace exposure scenario . 8
5.3 Existing inhalation toxicity testing guidelines . 9
6 Physicochemical parameters related to the toxicity of CNTs and CNFs .9
6.1 General . 9
6.2 Aerodynamic properties of aerosols for deposition of fibres . 9
6.3 Size and shape (including length, width, aspect ratio, state of aggregation/
agglomeration, and rigidity) . 10
6.4 Specific surface area . 11
6.5 Crystalline structure and defects. 11
6.6 Surface chemistry, functionalization, surface charge, impurities, and radical
generation/scavenging potential . 11
6.7 Biodurability. 12
7 Issues for the characterization of CNT and CNF aerosols .12
7.1 General .12
7.2 Characterization of physicochemical properties of CNT and CNF prior to aerosol
generation . 13
7.2.1 General .13
7.2.2 Size and size distribution . 13
7.2.3 Shape (rigidity and agglomeration/aggregation) . 14
7.2.4 Surface area . 14
7.2.5 Crystalline structures . 14
7.2.6 Surface chemistry, functionalization, surface charge, and radical
generation/scavenging potential . 14
7.2.7 Composition, purity, and impurities . 14
7.2.8 Biodurability (in vivo and in vitro tests) . 15
7.3 CNT and CNF aerosol characterization (sampling and measurement) .15
7.3.1 General .15
7.3.2 Size and size distribution of CNT and CNF aerosols . 16
7.3.3 The shape of CNT and CNF aerosols . 18
7.3.4 Crystalline structure and defects . 18
7.3.5 Surface chemistry. 18
7.3.6 Composition analysis . 19
7.3.7 Fibre density . 19
7.3.8 Concentration . 19
7.4 Direct and indirect measurement . 20
7.4.1 Direct measurement . 20
7.4.2 Indirect measurement . 21
Annex A (informative) Physicochemical properties of CNT associated with biological
activity .22
Annex B (informative) CNT and CNF aerosol monitoring instruments .23
Bibliography .26
iii
Foreword
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iv
Introduction
Inhalation is the primary route of exposure to aerosolised carbon nanotubes (CNTs) and carbon
nanofibres (CNFs). Exposure to CNTs or CNFs can occur in consumer settings as well as in occupational
settings. Occupational exposure to CNTs or CNFs can occur at all phases of the manufacturing, handling,
[1,2]
and formulation of the material into final products . Consumers are potentially exposed to CNTs
or CNFs released as products of degradation, weathering, or mechanical processes (e.g. grinding or
[3,4]
polishing) from consumer products that contain CNT or CNF embedded into a matrix .
Similar to other nanomaterials, the physicochemical properties of CNTs or CNFs are greatly diverse
in terms of diameter, length, shape, arrangement of carbon atoms, surface chemistry, defects, and
impurities. Their different physicochemical characteristics are responsible for different functional
properties such as mechanical, electrical, optical, and thermal properties. Many previous inhalation
toxicity studies of CNT and CNF aerosols reported various hazards from acute inflammation to
carcinogenicity and the toxicological responses to CNT and CNF aerosols vary depending on their
[5]
physicochemical characteristics .
Among the various physicochemical characteristics, morphological factors such as length and rigidity
[6,7]
have been suggested as key parameters related to the toxicity of CNT and CNF aerosols . CNT and CNF
[8]
aerosols can consist of individual primary fibres in the nanoscale and aggregated or agglomerated
[9]
structures, including those with diameters larger than 100 nm . Among various types of CNT and CNF,
the asbestos-like pathogenicity has been observed only in long (>5 μm) and rigid fibres, but not in short
[6]
or tangled CNT . Thus, a better understanding of the characteristics of generated CNT or CNF aerosols
in relation to toxicity end points is key for risk assessment and safer-by-design approaches.
The framework for material characterization for inhalation studies consists of (1) characterization
of as-produced (pristine) or supplied material, (2) characterization of administered material, (3)
[10]
characterization of material following administration, and (4) human exposure characterization .
This document focuses on the first two characterization needs, which include physicochemical
properties (e.g. size, size distribution, aggregation/agglomeration, and shape) and measurement of
concentration (e.g. mass, number, surface area, and volume). These parameters can be measured by
direct (online) or indirect (off-line) methods and each technique needs specific sampling procedures.
However, the limited technologies in the generation and characterization of nanofibres make it difficult
to perform inhalation toxicity studies, although the inhalation exposure to CNT and CNF is highly likely
[9,11] [8]
in the workplace , and research facilities , where they are in use. In this regar
...