SIST-TS CEN ISO/TS 21623:2018

SLOVENSKI STANDARD
kSIST-TS FprCEN ISO/TS 21623:2017
01-september-2017
Izpostavljenost na delovnem mestu - Ocena dermalne izpostavljenosti nanodelcem
ter njihovim agregatom in aglomeratom (NOAA) (ISO/PRF TS 21623:2017)
Workplace exposure - Assessment of dermal exposure to nano-objects and their
aggregates and agglomerates (NOAA) (ISO/PRF TS 21623:2017)
Exposition am Arbeitsplatz - Leitfaden zur Beurteilung der dermalen Exposition an Nano-
Objekten sowie deren Aggregaten und Agglomeraten (NOAA) (ISO/PRF 21623:2017)
Exposition sur les lieux de travail - Évaluation de l'exposition cutanée aux nano-objets et
à leurs agrégats et agglomérats (NOAA) (ISO/PRF TS 21623:2017)
Ta slovenski standard je istoveten z: FprCEN ISO/TS 21623
ICS:
13.040.30 Kakovost zraka na delovnem Workplace atmospheres
mestu
kSIST-TS FprCEN ISO/TS 21623:2017 en,fr,de
2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.

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kSIST-TS FprCEN ISO/TS 21623:2017
TECHNICAL ISO/TS
SPECIFICATION 21623
First edition
Workplace exposure — Assessment
of dermal exposure to nano-
objects and their aggregates and
agglomerates (NOAA)
Exposition sur les lieux de travail — Évaluation de l’exposition
cutanée aux nano-objets et à leurs agrégats et agglomérats (NOAA)
PROOF/ÉPREUVE
Reference number
ISO/TS 21623:2017(E)
©
ISO 2017

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COPYRIGHT PROTECTED DOCUMENT
© ISO 2017, Published in Switzerland
All rights reserved. Unless otherwise specified, no part of this publication may be reproduced or utilized otherwise in any form
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Contents Page
Foreword .iv
Introduction .v
1 Scope . 1
2 Normative references . 1
3 Terms and definitions . 1
4 Dermal exposure to NOAA — Evidence and exposure routes . 4
4.1 General . 4
4.2 Source domains . 4
4.3 Exposure routes . 5
5 Stepwise approach for assessment of dermal exposure to NOAA . 6
5.1 General . 6
5.2 Step 1: Desk evaluation . 7
5.2.1 Step 1A: Evaluation of toxicological hazard based on NOAA composition . 7
5.2.2 Step 1B: Screening for potential risks associated with dermal exposure to
insoluble (non-flexible) NOAA . 8
5.2.3 Step 1C: Screening for potential risks associated with dermal exposure
based on job title . .10
5.3 Step 2: Observation of potential for dermal exposure .11
5.4 Step 3: Additional observation of worker behaviour.11
5.5 Step 4: Quantification of NOAA .11
5.6 Step 5: Evaluation and review .12
Annex A (informative) Industries associated with use of nanomaterials or nano-
enabled products .13
Annex B (informative) How to determine skin disruption? .16
Annex C (informative) DeRmal Exposure Assessment Method (DREAM) .18
Annex D (informative) Inadvertent ingestion exposure .24
Annex E (informative) Exploring dermal exposure measurements of nanoparticles .27
Bibliography .31
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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 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 the following
URL: w w w . i s o .org/ iso/ foreword .html.
ISO/TS 21623 was prepared by the European Committee for Standardization (CEN) Technical Committee
CEN/TC 137, Assessment of workplace exposure to chemical and biological agents, in collaboration with
ISO Technical Committee ISO/TC 146, Air quality, Subcommittee SC 2, Workplaces atmospheres, in
accordance with the Agreement on technical cooperation between ISO and CEN (Vienna Agreement).
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Introduction
Dermal exposure assessment explores the dynamic interaction between environmental contaminants
and the skin. In contrast to inhalation exposure assessment, the assessment of dermal exposure
requires a different set of exposure considerations. During the last decades, the body of knowledge with
regard to dermal exposure has expanded for many types of substances, which amongst others resulted
in publications for the evaluation of dermal exposure to chemical substances that can be found, for
example, in CEN/TR 15278, CEN/TS 15279, and ISO/TR 14294.
Currently, engineered/manufactured nanomaterials and nano-enabled products are produced and
used on a wide scale. Occupational skin exposure to these substances can have biological relevance
to human health. Potential adverse effects include local skin effects, systemic toxicity following skin
absorption/uptake and inadvertent ingestion through the hand-to-mouth pathway. This document
provides guidance for the evaluation of potential dermal exposure to manufactured nano-objects, their
agglomerates and aggregates (NOAA).
This document is a compilation of the results of a pre-normative research project, executed under
Mandate M/461 for standardization activities regarding nanotechnologies and nanomaterials as issued
by the European Commission. This pre-normative research gives an overview of the mechanisms of
occupational dermal exposure to nanoparticles or nano-enabled products. This includes potential
concomitant for intake or uptake. It is based on relevant evidence of exposure for identified job
titles. Part of the pre-normative research comprised experimental work on the skin penetration
of nanoparticles, transfer of nanoparticles from a surface to the skin, and exploratory work on the
[4]-[6]
feasibility to quantify dermal exposure to NOAA .
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kSIST-TS FprCEN ISO/TS 21623:2017
TECHNICAL SPECIFICATION ISO/TS 21623:2017(E)
Workplace exposure — Assessment of dermal exposure to
nano-objects and their aggregates and agglomerates (NOAA)
1 Scope
This document describes a systematic approach to assess potential occupational risks related to
nano-objects and their agglomerates and aggregates (NOAA) arising from the production and use of
nanomaterials and/or nano-enabled products. This approach provides guidance to identify exposure
routes, exposed body parts and potential consequences of exposure with respect to skin uptake, local
effects and inadvertent ingestion.
This document also considers occupational use of products containing NOAA by professionals, e.g.
beauticians applying personal care products, cosmetics or pharmaceuticals, but does not apply to
deliberate or prescribed exposure to these products by consumers.
This document is aimed at occupational hygienists, researchers and other safety professionals to assist
recognition of potential dermal exposure and its potential consequences.
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.
EN 1540, Workplace exposure — Terminology
ISO 18158, Workplace air — Terminology
3 Terms and definitions
For the purposes of this document, the terms and definitions given in EN 1540, ISO 18158 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 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/TS 80004-2:2015, 3.4]
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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
dermal contact volume
volume containing the mass of the agent that contacts the dermal exposure surface (3.7)
Note 1 to entry: This is equivalent to the volume of the skin contaminant layer and for practical reasons
represents the volume of the compartment where the mass of the substance is all contained.
[SOURCE: CEN/TR 15278:2006, 2.2, modified — Note 1 adapted]
3.4
dermal exposure concentration
dermal exposure mass (3.6) divided by the dermal contact volume (3.3) or the dermal exposure mass
divided by the mass contained in the skin contaminant layer
Note 1 to entry: Dermal exposure concentration is expressed in g/l or g/kg or other appropriate units as
necessary.
[SOURCE: CEN/TR 15278:2006, 2.4, modified — Note 1 adapted]
3.5
dermal exposure loading
dermal exposure mass (3.6) divided by the dermal exposure surface (3.7) area
Note 1 to entry: For practical reasons, it can be expressed as mass of agent in an exposed part of the skin
contaminant layer divided by the surface area of that part.
[SOURCE: CEN/TR 15278:2006, 2.5]
3.6
dermal exposure mass
mass of agent present in the dermal contact volume (3.3)
Note 1 to entry: For practical reasons, it is defined by the amount of agent in g present in the skin contaminant
layer, or other appropriate units as necessary.
Note 2 to entry: The outcome of the process of dermal exposure, i.e. the contact, can be expressed by different
parameters of exposure.
[SOURCE: CEN/TR 15278:2006, 2.6, modified — Note 1 adapted]
3.7
dermal exposure surface
skin surface area where an agent is present
Note 1 to entry: For practical reasons, this is represented by a two-dimensional representation of the skin
2
contaminant layer in cm .
[SOURCE: CEN/TR 15278:2006, 2.7]
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3.8
nanocomposite
solid comprising a mixture of two or more phase-separated materials, one or more being nanophase (3.13)
Note 1 to entry: Gaseous nanophases are excluded.
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]
3.9
nano-enabled
exhibiting function or performance only possible with nanotechnology
Note 1 to entry: Potential release of NOAA from nano-enabled products is considered relevant in view of dermal
exposure assessment.
[SOURCE: ISO/TS 80004-1:2015, 2.15]
3.10
nanomaterial
material with any external dimensions in the nanoscale or having internal structure or surface
structure in the nanoscale (3.14)
[SOURCE: ISO/TS 80004-1:2015, 2.4]
3.11
nano-object
discrete piece of material with one, two or three external dimensions in the nanoscale (3.14)
Note 1 to entry: The second and third external dimensions are orthogonal to the first dimension and to each other.
[SOURCE: ISO/TS 80004-1:2015, 2.2]
3.12
nanoparticle
nano-object (3.11) with all three external dimensions in the nanoscale (3.14) 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 three times), terms such as
nanofibre or nanoplate may be preferred to the term nanoparticle.
[SOURCE: ISO/TS 80004-2:2015, 4.4]
3.13
nanophase
physically or chemically distinct region or collective term for physically distinct regions of the same
kind in a material with the discrete regions having one, two or three dimensions in the nanoscale (3.14)
Note 1 to entry: Nano-objects embedded in another phase constitute a nanophase.
[SOURCE: ISO/TS 80004-4:2011, 2.12]
3.14
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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3.15
perioral region
perioral area
area surrounding the mouth
Note 1 to entry: See Reference [10].
3.16
skin contaminant layer compartment
SCL
three-dimensional compartment on top of the stratum corneum (SC) of the human skin where sebum
lipids, sweat and additional water from transepidermal water loss (TEWL) are present, including
products from cornification and unshed corneocytes
3.17
source domain
SD
generation mechanism that determines particle emission characteristics for a particular life cycle stage
Note 1 to entry: Different mechanisms determine the emission rate, particle size distribution, source location
and transport of NOAA during the various life cycle stages (synthesis, downstream use, application or treatment
[11]
of products and end of life) .
4 Dermal exposure to NOAA — Evidence and exposure routes
4.1 General
The mechanisms of occupational dermal exposure and evidence for skin penetration and local skin
effects have been defined in this document.
The relevance of dermal exposure to NOAA outlined in this document considers the following outcomes:
a) potential for penetration and systemic effects;
b) absorption by the stratum corneum (SC) and potential for local (skin) effect;
c) inadvertent ingestion.
4.2 Source domains
A conceptual source-receptor framework suitable for nanomaterials and nano-enabled products has
been developed. This links the source domains concept, as developed for modelling occupational
[11]
inhalation exposure to NOAA with the conceptual framework for dermal exposure. The dermal
exposure framework describes the various pathways, underlying mechanisms, and potential
[12]
consequences for NOAA contamination of the skin .
The source domains (SD) reflect different mechanisms of release and consequently possible different
nature of released aerosols and are thus associated with the life cycle stages of NOAA.
— SD 1: During the production phase (synthesis) prior to harvesting the bulk material, point source
or fugitive emission, e.g. emissions from the reactor, leaks through seals and connections, and
incidental releases, can take place. In these cases, discrete nanoparticles and homogeneous and
inhomogeneous agglomerates will be formed.
— SD 2: During the manufacturing of products, the handling and transfer of bulk manufactured
nanomaterial powders with relatively low energy nanoparticles can be released, e.g. during
collection, harvesting, bagging/bag dumping/bag-emptying, dumping, scooping, weighing,
dispersion/compounding in composites, etc. However, the powders are already in agglomerated
stage and high shear forces are needed for deagglomeration. Therefore, the majority of the released
particles will be agglomerates.
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— SD 3: During further processing or in the use phase of a ready-to-use nano-product, release can be
expected during the relatively high-energy dispersion/application of
— solid, powdery or (liquid) intermediates containing highly concentrated (>25 %) nanoparticles,
e.g. pouring/injection moulding, (jet) milling, stirring/mixing. As higher shear forces can occur
during high energy dispersion, de-agglomeration can occur, and
— relatively low concentrated (<5 %) ready-to-use products, e.g. application of coatings or spraying
of solutions that can form nano-sized aerosols after evaporation of the liquid phase component,
usually of mixed composition.
— SD 4: During the use phase of a product or its end-of-life phase, activities resulting in fracturing and
abrasion of manufactured nanoparticles-enabled end products at work sites can result in release
of NOAA, e.g. a) low energy abrasion, manual sanding or b) high energy machining (e.g. sanding,
grinding, drilling, cutting, shredding, etc.). High temperature processes like burning are included.
In case of release, most likely multi-composed aerosols will be emitted, and in case of machining
also matrix-bound nanoparticles, whereas during thermal processes nanoparticles can also be
formed following nucleation and condensation of vapours.
Process conditions will determine the release process (i.e. mechanism, form, composition and level
of release) and together with handling the process of skin contamination (i.e. through direct contact,
deposition from the air compartment or transfer from contaminated surfaces). In addition, professional
use of personal care products can result in direct contact of the product with the skin. Transformation
(e.g. change in particle size distribution, agglomeration, etc. of the nanomaterial on the skin compared
to the release) can occur either directly by the exposure process or route (e.g. transfer or direct contact),
or during time of residence in the air compartment.
The level of exposure, either dermal exposure concentration, mass or surface area of exposed (body)
location(s) will be determined by the underlying processes of release and exposure. In addition,
the exposure time, characteristics of the substances and skin physiological conditions need to be
considered.
4.3 Exposure routes
Observational studies show that the most highly exposed body parts are the hands, and the
[13]-[15]
predominating exposure pathway is nanoparticle transfer from contaminated surfaces .
However, deposition of airborne aerosols or direct contact with products containing NOAA can also
contaminate other body parts (e.g. forearms and forehead). Laboratory experiments carried out
as part of the pre-normative research, showed that transfer efficiency for nano-size particles was
approximately 30 times higher than that of micron-size particles, and showed for each particle size that
the higher the log-transformed loading, the lower the transfer efficiency (after accounting for particle
[4][6]
size) . Location of the exposure is of particular interest, since both the thickness of the SC and the
density of the hair follicles varies substantially over body locations, which is an important parameter
[16]-[19]
with regard to potential penetration and local effects of nanoparticles through the skin . In
addition to skin physiology, skin conditions and time of contact, the actual contact site is also relevant
[20]
for potential inadvertent oral exposure due to hand-to-mouth contact .
Dermal exposure risk by industrial sector and job title are based on reported use of nanomaterials and
nano-enabled products (see Annex A). No indication on the level of dermal exposure can be extracted
from available information. However, based on the form of NOAA and nano-enabled products present
in the work environment and the type of activities performed by the worker, it is possible to have a
first indication of the potential for dermal exposure occurring at the workplace and the accompanying
potential risk.
Nanoparticles on the skin can penetrate SC reaching viable epidermis using different pathways:
a) through sweat glands and hair follicles, which is probably the most efficient way for penetration
and permeation of NOAA;
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b) the intercellular route, which is only possible for very small NOAA (<4 nm) or in damaged skin
condition;
c) the intracellular pathway is unlikely to be relevant for NOAA, but might be relevant for released
(metal) ions.
Present evidence suggests that only very small particles (<4 nm) can penetrate intact skin, whereas
insoluble, nonreactive particles with sizes >45 nm will not be absorbed by the intact skin. Penetration
in the intermediate size ranges was only observed in the case of a disrupted skin where the barrier
function of the skin was affected. Flexible/non-rigid NOAA, e.g. liposomes and micelles, especially
spherical lipid structures, can deviate from this categorization since ultra-deformable liposomes,
despite their nominal size of normally around 100 nm to 200 nm, can squeeze through the much
[21]
narrower SC lipid bilayers due to their flexibility .
When handling liquid products at the workplace (e.g. by means of stirring, spraying, etc.) or due to
vapour condensation, nano-scale droplets containing NOAA can be formed. Depending on the volatility
of the substance, these droplets can easily evaporate or stay in the air for a longer period, and can
[22]
even increase in volume over time due to condensation processes . When these droplets come into
contact with the skin (resulting in moistening of the skin), the chemical composition of the liquid, its
skin-damaging properties and percutaneous absorption characteristics have to be taken into account,
regardless of the droplets’ original dimensions. Particular attention shall be given to nano-scale
droplets consisting of liquid dispersions, that can release solid NOAA (e.g. metal salts) after evaporation
of the solvent.
In case of exposure to metal (oxide) nanoparticles (Ni, Cr, Co, etc.) or carbon-based nanoparticles with
metal catalytic residues, the potential release of ions can induce local skin effects (e.g. irritation and
contact dermatitis), which can be enhanced by a relatively long time of residence in case of penetration
of NOAA into the hair follicles. Allergic contact dermatitis is expected for certain types of nanoparticles,
[23]
yet not much data exists in the peer-reviewed literature .
The integrity of SC and its damage due to pre-existing disease and other work-related conditions
(e.g. wet work and abrasion) can be assessed relatively easily with subjective assessment methods,
including questionnaires (see Annex B). Biophysical measurements of skin barrier, for instance
measuring transepidermal water loss (TEWL), can have some utility in the workplace but methods are
not well established. Currently, no data are available to evaluate the potential for oral intake of NOAA
due to hand-mouth contact. It is assumed that determinants of inadvertent ingestion of NOAA do not
differentiate from those for conventional chemicals, which means that inadvertent ingestion exposure
by indirect contact depends on
— the mass loading of substance on hand or object,
— the transfer efficiency from hand or object to the perioral area (proportion),
— transfer efficiency from the perioral area to the oral cavity (proportion),
— the surface area of the hand or object involved in contact (proportion), and
— the frequency of hand- or object-to-perioral contacts.
5 Stepwise approach for assessment of dermal exposure to NOAA
5.1 General
The assessment of dermal exposure to NOAA shall begin with an initial screening assessment
considering the following:
— identification of hazards;
— identification of who is involved and how;
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