ISO/TS 21623:2017

TECHNICAL ISO/TS
SPECIFICATION 21623
First edition
2017-11
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)
Reference number
©
ISO 2017
© ISO 2017, Published in Switzerland
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ii © ISO 2017 – All rights reserved

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
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
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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
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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
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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: www.iso.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).
iv © ISO 2017 – All rights reserved

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 .
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 https://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]
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
contaminant layer in cm .
[SOURCE: CEN/TR 15278:2006, 2.7]
2 © ISO 2017 – All rights reserved

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, modified — Note 1 added]
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, modified — Notes 1 and 2 deleted]
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, 2.5]
3.12
nanoparticle
nano-object (3.11) with all 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]
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.
4 © ISO 2017 – All rights reserved

— 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;
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, nanoscale 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 nanoscale 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;
6 © ISO 2017 – All rights reserved

— evaluation of risks and decisions on precautions;
— recording of significant findings;
— review of risk assessment and update if necessary.
With respect to assessment of dermal exposure to NOAA in the workplace, a stepwise approach is
presented to assess the situation in the workplace in a systematic manner with a focus on
— potential for exposure based on a potential for release, and
— potential for skin disruption.
In Figure 1, an overview of this stepwise approach is given. After each step, a conclusion shall be made
whether the situation at the workplace is considered to be safe based on the information that is gathered
during that part of the assessment. If the situation is not considered to be safe, one shall proceed to the
following step of the assessment.
Figure 1 — Overview of stepwise approach for assessment of dermal exposure to NOAA
Below, for each of the steps more details are given, as well as a tool to perform that particular part
of the assessment in practice. Where relevant, “traffic light” colours are applied in Figures 1, 2 and
3 to indicate the level of concern with regard to the (potential) risk (green = no or low concern,
orange = moderate concern and red = high concern). Each step in the approach can result in a conclusion
that dermal exposure to NOAA is not considered to result in a health risk for workers, after which one
proceeds to step 5 (evaluation).
5.2 Step 1: Desk evaluation
5.2.1 Step 1A: Evaluation of toxicological hazard based on NOAA composition
Step 1A consists of a primary (desk) evaluation of the occurrence of possible health risks based on the
NOAA composition/characteristics. In Figure 2, a schematic overview of this evaluation and the further
course of the overall assessment is given.
Attention shall be given to
— metal NOAA, since the potential release of ions can induce local skin effects (e.g. irritation and
contact dermatitis) and absorption of toxic or sensitizing metals,
— NOAA with metal catalytic residue, since potential release of ions can induce local skin effects (e.g.
irritation and contact dermatitis) and absorption of toxic metals,
— flexible/non-rigid NOAA, since due to their flexibility liposomes and micelles can penetrate and
permeate the intact skin at sizes >4 nm,
— liquid nanoscale droplets containing emulsified or dissolved NOAA, which can act as discrete nano-
objects, either directly or after evaporation of the solvent, and
— other toxic substances, e.g. carcinogenic substances, mutagenic substances.
In case of “high hazard” NOAA, further evaluation as part of step 1A is necessary. Dissolution of toxic
or sensitizing substances in synthetic sweat shall be evaluated under physiological relevant conditions
(e.g. at 32 °C to mimic the temperature of the hands).
NOTE Arrows in colour indicate variation in level of concern with regard to (potential) risk: Green means no
or low concern, orange means moderate concern and red means high concern.
Figure 2 — Schematic overview of primary evaluation based on composition of NOAA and
following steps
5.2.2 Step 1B: Screening for potential risks associated with dermal exposure to insoluble (non-
flexible) NOAA
For relevant scenarios, screening for potential risks associated with dermal exposure to insoluble (non-
flexible) NOAA shall be performed by means of an initial (desk) assessment. This screening shall be
performed based on the scheme as presented in Figure 3.
Figure 3 illustrates a conceptual model for the assessment of potential risks due to exposure to NOAA
in various scenarios. At the left hand side of the figure, the lines provide a simplified overview of the
relevant phases of the process of screening for potential risks. It starts with indicating which source
domains can be involved, and the relationship of these source domains with a characterization of the
released NOAA based on the relevant release mechanism(s). Next, it indicates which would be the major
mechanisms for transport of the NOAA to the skin surface and the related potential for alteration of
the NOAA with regard to size. The next part of the figure shows the potential for skin exposure, both
8 © ISO 2017 – All rights reserved

with regard to exposure level and body location. Depending on the estimated particle size (i.e. initial
particle size in combination with possible alterations during transport), the type of NOAA (metal or
non-metal) and the conditions of the skin, the potential for either skin penetration or the occurrence
of local effects can be estimated. Based on evaluation of exposure literature, it is assumed that only
in case of direct deposition of relatively low concentrations of NOAA from the air compartment, the
[4],[5]
initial size distribution during release will not be affected . In this situation, there is a potential
for the presence of NOAA with particle sizes below 20 nm, which results, depending on the condition
of the skin, in a potential for direct penetration of the NOAA through the skin. For other scenarios, skin
penetration is considered to be irrelevant and the major risks would be local skin effects due to release
of Me-ions or inadvertent ingestion. Note that flexible NOAA, e.g. micelles and liposomes, are excluded
from this scheme.
As is shown in Figure 3, internal exposure (uptake) of NOAA due to the dermal route is very specific and
mainly relevant for either very small NOAA or the occurrence of disrupted skin. Otherwise uptake of
NOAA due to inadvertent ingestion is the main route of exposure.
All possible (combinations of) exposure processes and critical sizes shall be considered when applying
the scheme. In case this screening step results in “negligible or no skin penetration” and no flagged job
titles are present (see step 1C), there is no need to proceed to the next step in the stepwise approach.
NOTE 1 In Figure 3, “traffic light” colours are used to indicate variation in level of concern with regard to
(potential) risk: Green means no or low concern, orange means moderate concern and red means high concern.
Blue is used for two phases (horizontal lines) in the scheme to indicate in what form NOAA are available (either at
the source or on the skin).
All of the possible exposure processes and critical sizes should be considered. In case of metal NOAA,
the “metal NOAA” path as well as the size paths should be followed.
NOTE 2 Relevant release mechanisms include among others (the influence of) pressure, forces, abrasion and
heat. In general, it is assumed that for instance if high pressure/forces/heat is applied, the potential for release of
NOAA is also high.
[4][6]
NOTE 3 Proposed critical size categories are based on experimental data .
Figure 3 — Scheme for screening for potential risks associated with dermal exposure to
insoluble (non-flexible) NOAA
5.2.3 Step 1C: Screening for potential risks associated with dermal exposure based on job title
For relevant scenarios, screening for potential risks associated with dermal exposure to NOAA shall be
performed by means of an initial (desk) assessment. This screening shall be performed based on
— job titles with relevant dermal exposure to NOAA, and
— in case of relevant dermal exposure to NOAA, job titles with high risk of skin disruption (see Table 1);
Table 1 — Job titles with high risk for skin disruption in sectors with known use of
nanomaterials (non-exhaustive)
Sector Job title Example of nanomaterials/products
Health care Dental practitioner/assistant/technician Nanocomposites
Nurses Pharmaceuticals containing nanomaterials
Personal care Hairdresser Variety of personal care products
Beauticians/cosmetician Variety of personal care products
NOTE  Job titles with reported high incidence of skin diseases were linked to reported use of nanomaterials or nano-
[4]
enabled products or exposure to NOAA to flag potential high-risk job titles with respect to dermal exposure .
10 © ISO 2017 – All rights reserved

Table 1 (continued)
Sector Job title Example of nanomaterials/products
Construction Construction painters Coatings, paints
Concrete repair workers Mortars
Cleaning Cleaners Cleaning and dirt repellent coatings
Automotive Car (body) repair workers Primers, paints, nanocomposites
NOTE  Job titles with reported high incidence of skin diseases were linked to reported use of nanomaterials or nano-
[4]
enabled products or exposure to NOAA to flag potential high-risk job titles with respect to dermal exposure .
5.3 Step 2: Observation of potential for dermal exposure
Additional observations of worker behaviour shall indicate where there is potential for dermal exposure
(or inadvertent ingestion). These observations provide a first indication of the frequency of contacts
with materials and surfaces and on exposed body parts.
The DeRmal Exposure Assessment Method (DREAM) can be used to assess the potential for dermal
[1]
exposure by a structured observational approach, either in its complete form or in a simplified
[15]
form , as well as other methods or models as they become available. The DREAM method focuses on
identification of the main exposure processes and main body parts involved. More information about
DREAM is given in Annex C. If there is potential for dermal exposure based on these observations,
proceed to step 3a and 3b.
5.4 Step 3: Additional observation of worker behaviour
a) An observational assessment shall be made to check the appropriate use of work clothing and/or
protective clothing and gloves. Appropriate use includes the proper fit, check on uncovered body
[24]
surface, consistent use over work tasks and proper removal . In addition, the condition of the
skin shall be checked with respect to the presence of cuts, redness, swelling, oozing/crusting,
thickening, cracking and dryness. Subjective evaluation methods, for instance, the modified Hand
Eczema Severity Index (HECSI) (see Annex B) could provide a simple tool to assess skin barrier
function in relation to the likelihood of dermal uptake of nanoparticles. Another option is the
measurement of TEWL (see Annex B). If exposed skin areas are present and high potential for skin
barrier disruption is apparent, proceed to step 4a.
b) For indications of perioral contacts, the method as described by Reference [25] can be used. With
regard to perioral contacts (and thus inadvertent ingestion) the process of transfer (both from
surfaces to the hands, from hands to the perioral region and from contaminated objects to the
perioral region are important. More information about the conceptual model integrating dermal
[20]
exposure and inadvertent ingestion and the ingestion exposure assessment tool (IEAT) can be
found in Annex D. If there is potential for perioral contacts, proceed to step 4b.
5.5 Step 4: Quantification of NOAA
Although not considered obligatory, quantification of NOAA is considered to be a valuable addition in
this stepwise approach. The type of quantification depends on the exposure route.
a) Characterization and quantification of dermal exposure to NOAA in the context of potential uptake
through the skin requires a sophisticated sampling (e.g. tape lifting) and detection methods (e.g.
electron microscopy of samples lifted from the skin). Appropriate methods are needed to ensure key
information with regard to size and morphology can be assessed (see Annex E). If skin penetration
has the potential to occur, the use of samples lifted from the skin combined with scanning electron
microscopy (SEM) analysis is recommended to characterize the NOAA on the skin in terms of
size, morphology, and chemical composition. However, the electronic microscopy (EM) analysis of
samples lifted from the skin by tape lifts technique is currently still very challenging.
b) If there is potential for perioral contacts, an indication of the mass loading of the hand(s)
and/or perioral region can be assessed by applying conventional removal methods as described in
CEN/TS 15279 and ISO/TR 14294. Alternatively, surface wipes can be used for an indication of the
surface loading.
In case of high hazard NOAA that dissolve in synthetic sweat (see step 1A), it is advised to also evaluate
the level of contamination of surfaces (benches, tools, etc.) in the workplace by means of surface
wipes. In addition, it is advisable to evaluate the internal exposure to these substances by means of
biological monitoring (if available, e.g. for As, Cr, Co, Ni in urine) for exposed workers as part of the risk
[26]-[29]
assessment . Please note that in case of biomonitoring, no distinction can be made between the
(relative) contribution of all exposure routes (dermal, oral or inhalation). However, this information is
considered relevant in relation to systemic health effects.
5.6 Step 5: Evaluation and review
It is important to evaluate the outcome of the risk assessment. This includes prioritization of the
risks, formulating an action plan for risk mitigation, documenting the findings and the action plan
(if relevant), and informing the workers involved about the outcome and actions. Furthermore, few
workplaces stay the same. Introducing new equipment, substances and procedures could lead to new
hazards. Therefore, the risk assessment shall be reviewed at appropriate time intervals, and updated if
necessary, including the assessment of dermal exposure to NOAA (feedback loop).
12 © ISO 2017 – All rights reserved

Annex A
(informative)
Industries associated with use of nanomaterials or nano-enabled
products
In order to get an overview of the industrial sectors where nanomaterials and nano-enabled products
are most frequently manufactured and used, a literature search was conducted to identify national
and international surveys and reviews investigating this topic. Based on this literature search, the
use of NOAA seemed to be more widespread in some of the sectors (for instance ICT/Electronics,
healthcare, construction, surfaces and coatings, textiles and shoes, cosmetics and personal care,
automotive/automobile) than in others, indicating that the number of workers (potentially) exposed to
[4]
NOAA will probably be the highest in these sectors as well .
Table A.1 — Industries associated with use of nanomaterials or nano-enabled products (list is
non-exhaustive)
Sector/industry Product
Electronics, computers (incl. display), electrotechnics, electronical
devices, information and communications technology (ICT)
Sensors, microelectronics
Information and communications
Magnetics and magnetic materials
technology/electronics
Quantum computing
(Lithium-ion) batteries
Lights
(Renewable) energy
Fossil fuel power plants
Power-energy storage, distribution and transmission
Water purification, filtration and desalination
Sensing
Energy and environment/
green nanotechnology/ Environmental remediation/air emissions reduction
energy applications
Catalysis
Photovoltaics
Optics and optical devices
Natural and green products
Photonics and photonic devices
Nanomedicine: drug-delivery vehicles, contrast agents and diagnostic
devices
Healthcare
Textiles for medical applications
Aerospace/aviation Aerospace/aviation
Table A.1 (continued)
Sector/industry Product
Cement/concrete/production of wet concrete/concrete repair/concrete
prefab
Steel
Wood
Milling machines
Construction
Applications for construction
Insulation material
Coatings and paint
Infrastructure
Masonry and building materials
Stone —
Coatings (paints), surface coating surface modification
Paint production
Surfaces and coatings
Polish (other)
Painters/coaters
Ceramics and glass Ceramics and glass production/application
Security/defence Security/defence
Sustainable chemistry – catalysts
Chemical industry
Chemicals industry (production)
Food production, processing, safety and packaging
Food industry
Nutrition
Textiles
Shoes
Tex
...