Ecotoxicology and Environmental Safety 207 (2021) 111458

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Ecotoxicology and Environmental Safety

journal homepage: www.elsevier.com/locate/ecoenv

Research paper

Regulatory developments and their impacts to the nano-industry: A case

study for nano-additives in 3D printing
Alicia A. Taylor a, *, Elaine L. Freeman b, Merel J.C. van der Ploeg c, 1
a
Exponent, Inc., 475 14th Street, Suite 400, Oakland, CA 94612, USA
b
Exponent, Inc., 1150 Connecticut Avenue NW, Suite 1100, Washington, District of Columbia 20036, USA
c
Exponent International Ltd., The Lenz, 1st Floor Hornbeam Park, Harrogate, North Yorkshire HG2 8RE, UK

A R T I C L E I N F O A B S T R A C T

Edited by: Professor Bing Yan Nanotechnology has increasing applications in numerous markets, particularly in additive processing (3D
printing) and manufacturing, which is important for consumer products, medical devices, construction, and
Keywords: general research and development across many other industries. Nanomaterials are desirable in many products
Additive manufacturing due to their unique properties, but those same properties have made evaluating the risk and regulation of these
3D printing
materials challenging. For risk-based regulations, new applications and nanomaterials should be assessed for
Hazard assessment
both human and environmental hazards and exposure to ensure protection. In general, many risk assessments to
Exposure assessment
Stewardship date have focused on the non-nano versions of chemicals. The lack of guidance on assessing the hazard and
Risk assessment exposure of nanomaterials in 3D printing is apparent, and these areas of assessment are actively being evaluated.
Industry in most cases will now need to provide specific additional information for assessing the risk of nano­
materials in 3D printing. This review paper focuses on the use of nanomaterials in 3D printing for industrial and
manufacturing applications, summarizes the current literature on human health and safety related to 3D printing
and inhalation exposure, and the regulations relating to 3D printing in the U.S., Canada, and Europe for this
industry.

1. Introduction
In 2013, between 260,000 and 390,000 metric tons of nanomaterials
were produced worldwide (Keller et al., 2013) and by 2022 - 2025, the
global nanomaterials market will be worth $55 billion to $175 billion
dollars (Inshakova and Inshakova, 2017; Research and Markets, 2016).
In 2012, the 3D printing market was worth $0.29 billion (Canalys Inc,
2014) and grew to approximately $10.4 billion in 2019 (AMFI, 2020). It
is anticipated that the 3D printing market will double in size approxi­
mately every three years (AMFI, 2020). Applications for 3D printing
include rapid prototyping of devices, additive manufacturing, bio-
printing, and use in industries such as medical devices, apparel, elec­
tronics, automotive, and construction. Nanomaterials are commonly
used in 3D printing (Magdassi and Kamyshny, 2017). The top ten pro­
duced nanomaterials (>100 tons/year) are used in a number of in­
dustries, including automotive, catalysts, electronics and optics, energy
and environment, coatings, paints and pigments, personal care products,
and healthcare devices (Keller and Lazareva, 2014). At this time,
nanomaterial regulations are still emerging, though many early regu­
lations were passed approximately a decade ago.
Regulatory agencies’ concern with nanoscale materials exists due to
their unique properties and lack of understanding of the potential for
exposure, toxicity, and bioavailability, and other environmental con­
cerns stemming from the manufacture and use of nanomaterials. All risk-
based regulations assess not only the potential hazards of nanomaterials
but also the potential exposure to nanomaterials. Risk-based regulatory
assessments include all aspects of nanomaterial production and use,
including 1) the manufacture of nanomaterials, 2) the manufacture of
products containing nanomaterials, 3) the use of products containing
nanomaterials, and 4) lifecycle assessments including disposal or recy­
cling of nano-enabled products. Due to limitations in the availability of
hazard and exposure data for nanomaterials, especially a lack of hazard
and exposure assessments to nanomaterials during 3D printing, the risk
assessment process for nanomaterials is still developing.
Consumers likely already handle products including nanomaterials
on a daily basis, such as clothing, sporting equipment, cleaning

* Corresponding author.
E-mail addresses: ataylor@exponent.com (A.A. Taylor), efreeman@exponent.com (E.L. Freeman), merel.van.der.ploeg@ctgb.nl (M.J.C. van der Ploeg).
1
Current address: Dutch Board for the Authorisation of Plant Protection Products and Biocides (CTGB), Bennekomseweg 41, 6717 LL Ede, The Netherlands.

https://doi.org/10.1016/j.ecoenv.2020.111458
Received 8 July 2020; Received in revised form 1 October 2020; Accepted 3 October 2020
Available online 29 October 2020
0147-6513/© 2020 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license
(http://creativecommons.org/licenses/by-nc-nd/4.0/).
A.A. Taylor et al.
products, cosmetics, paints, and personal care products (PEN, 2017).
Within these industries, incidental nanomaterial exposure may occur
but has previously been regulated as exposure to ultrafine particles
(UFPs) like those generated from car exhaust and regulated in the
automotive industry. The definition of UFP can vary from a size of < 2.5
µm (PM2.5) (Zhu et al., 2002) to a particle with a size range of < 1 µm
(Zonteck et al., 2016), which includes particles in the nanoscale size
range. The same challenge also exists for defining nanomaterials based
on a size range, and the lack of harmonization in the definitions for
small-scale particles is one major challenge with nano-regulations.
A harmonized definition of “nanomaterial” should include all forms
and uses of particles categorized in the nanoscale size range. The
generally accepted definition of a nanomaterial has been similar across
various governmental agencies, though it has not been part of official
regulatory decisions. The Organisation for Economic Co-operation and
Development (OECD), the European Commission, and the Occupational
Safety and Health Administration (OSHA) all define a nanomaterial as
1–100 nm in size in at least one dimension (OECD, 2017; EC, 2011;
OSHA, 2017a). Various other institutes and countries also define
nanomaterials as having a size of 1–100 nm, including the International
Organization for Standardization (under ISO/TS 80004-2:2015; ISO
2015), Health Canada (Health Canada, 2017b), China (with B/T 19619-
2004 (Jarvis and Richmond, 2011; ISO, 2013) and Japan (Ministry of
Health, 2008). Finally, the European Union defines nanomaterial as a
natural, incidental, or manufactured material containing particles,
either unbound or as an aggregate, where 50% or more of the particles in
the size distribution have one or more external dimensions that are in
the range of 1–100 nm (EU, 2011).
In the USA, nanomaterials are defined not only by size. The current
Toxic Substances Control Act (TSCA) for nanomaterials (United States
Environmental Protection Agency, U.S. EPA, 2017a) defines a nano­
material as a material that has been created as a new material having
unique or novel properties: “Unique and novel properties mean any size-
dependent properties that vary from those associated with other forms
or sizes of the same chemical substance, and such properties are a reason
that the chemical substance is manufactured or processed in that form or
size.” The new TSCA nanomaterial definition designates that the mate­
rial is purposefully manufactured as a material with unique size-
dependent characteristics differing from the characteristics of the
same bulk-scale material. These definitions are important for under­
standing how nanomaterials used in 3D printing may be regulated based
on their form.
This paper examines human exposure scenarios and human hazard
assessments for nanomaterials used in, or produced by, 3D printing at
the industrial scale. 3D printers use nanomaterials in the feedstock and
generate potential incidental inhalation and dermal exposure pathways
during the printing process. Inhalation exposures to nanomaterials
during some 3D printing processes have been studied in the past few
years (Azimi et al., 2016; Stephens, 2013; Zonteck et al., 2016). The
current regulation landscape will have a large impact on industries using
additives and 3D printing. Regulation in this industry will largely be
driven by nanomaterials generated as by-products with potential for
worker exposure, rather than nanomaterials found in the feedstocks for
3D printing.
With the recent standardization of methods for testing nanotoxicity
and assessing physicochemical properties (OECD, 2017), risk assess­
ments for nanomaterials are now needed to conduct a comprehensive
review of pathways and exposures to assess the overall risk. Risk as­
sessments used in industry should also consider proactive product
stewardship of nanomaterials to further ensure safe uses of nano­
materials and better manage both human and environmental exposures.
1.1. Nanomaterials used in 3D printing
Nanomaterials are found in feedstocks for 3D printers. They may be
specifically added for their physicochemical (Ko et al., 2010) or
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Ecotoxicology and Environmental Safety 207 (2021) 111458
microbial properties (Álvarez-Paino et al., 2017; Rajan et al., 2016) and
nanomaterials may also be created during the 3D printing process.
Popular nanomaterials used in 3D printing include aluminum oxides and
zirconium dioxide (Nau and Scholz, 2019). 3D printing is a type of ad­
ditive manufacturing, which is defined as a process to build a structure
layer by layer using a data template, or bluprint, uploaded into a ma­
chine with a lazer and feedstock (Dutta and Froes, 2017). 3D printers
work by replicating an object through the addition of successive layers
of a material (UVM, 2020). 3D printing is popular in industrial and
manufacturing applications, examples include commercial production
of apparel and parts for automobiles and aircraft (Kalisher, 2016; Klein
et al., 2013). 3D printing is used in many settings including large
commercial-scale applications, industries developing prototypes, spe­
cialty part manufacturing, architectural and engineering applications,
do-it-yourself home laboratories, and university laboratories. 3D print­
ing is ideal for quick turnaround of prototypes or small-scale
manufacturing, and this technology has made early production of pro­
totypes easier and more accessible to numerous markets.
Exposure to nanomaterial by-products released from 3D printers may
occur in numerous industries, such as aerospace, architecture, auto­
motive, commercial and consumer products, art, and dentistry (Kalisher,
2016). Exposure in these work spaces have not been characterized. In a
survey of 100 industrial manufacturers in 2014, it was found that 30% of
industrial manufacturing companies were experimenting with 3D
printing and 25% of manufacturing companies were using 3D printing
for prototypes (PWC, 2014). The speed at which 3D printing has been
adopted indicates that a thorough characterization of exposure potential
is necessary for worker health and safety.
2. Current knowledge on exposure and hazards
The scientific community still does not have a good understanding of
the potential health effects from exposure to different types of engi­
neered nanomaterials (HSE, 2017). Despite nanomaterials being used in
many products for over a decade (Hansen et al., 2009), challenges exist
for developing regulations, risk assessments, and other guidelines for
worker, consumer, and environmental health and safety. This is true for
the existing worker focused nano-regulations. The OECD stated that:
“Due to their size, manufactured nanomaterials may require additional
testing beyond the standard suite of tests used for other chemicals, to
ensure that the impact on human health and the environment is fully
understood” (OECD, 2017). The standing opinion that the hazards of
nano-versions of chemicals are the same as the non-nano versions is
currently under re-evaluation due to their novel properties as well as the
size of the nanomaterials. Key areas essential for understanding health
risks include routes of exposure, how nanomaterials are introduced into
the body, and the ways in which nanomaterials interact with the body’s
biological systems (OECD, 2017). Balancing the need for hazard infor­
mation on nanomaterials without relying solely on animal testing is a
challenge. In vitro testing may also be used for hazard determinations,
though standardization for in vitro methods are not as robust as in vivo
tools; this is because valiation and international acceptance of in vitro
testing has been slow. In vivo methods have traditionally been relied
upon for risk assessments using animal experiments to develop no
adverse effect and low adverse effect levels.
Hazard exposure must also take into consideration acute versus
chronic exposures. Therefore, in addition to animal testing, a focus for
any future hazard assessment of nanomaterials is to develop sustainable
and standardizable methods to determine these hazards without animal
testing, using read-across testing or physical-chemical properties. To
ensure the tests used to address the safety of nanomaterials are consis­
tent and defensible, the OECD’s Working Party on Manufactured
Nanomaterials (WPMN) launched the Sponsorship Programme for the
Testing of Manufactured Nanomaterials (Testing Programme) in
November 2017 (OECD, 2017). This Testing Program verifies the testing
methods used on nanomaterials. With the establishment of these OECD
A.A. Taylor et al.
harmonized testing guidelines for nanomaterials and OECD’s continued
efforts to identify alternatives to animal testing specific to nano­
materials, some tools are available to begin evaluating nanomaterial
hazards. The European Union recently issued a NanoREG Framework
and NanoReg Toolbox for the Safety Assessment of Nanomaterials. The
NanoREG framework aims to support regulatory authorities and in­
dustry in addressing the human and environmental risk of nanomaterials
(Gottardo et al., 2017). The NanoReg Toolbox provides a freely acces­
sible inventory of ready-to-use and publicly available tools for nano­
material safety assessments (Paula et al., 2018). Furthermore,
Promoting the Implementation of Safe by Design (PROSAFE) a joint EU
effort aims to transfer the principles from NANoREG to other member
states and non-EU states (EC, 2020).
Various scientific articles have taken on the topic of hazard and risk
assessment of nanomaterials. Fadell et al. (2018) discusses mechanism-
based hazard assessment of nanomaterials, including high-throughput
screening platforms and emerging tools for risk assessment and risk
management for humans and the environment. Spinazze et al. (2019)
published a probablilistic health risk assessment for graphene nano­
platelets. Landsiedel et al. (2017) proposed a Decision-making framework
for the grouping and testing of nanomaterials (DF4nanoGrouping) in which
grouping and targeted testing of nanomaterials are conducted and
included case studies. Furthermore, a peer-reviewed nanoGRAVUR
framework was developed to fill several data gaps found in the European
PROSAFE effort (Wohlleben et al., 2019).
2.1. Exposure scenarios and potential hazards
Only one peer-reviewed article was identified that discusses hazards
associated with additive manufacturing (Roth et al., 2019). The study
lists six types of 3D printing processes, the most common feedstock
materials used, the form of the feedstock (liquid, polymer, powder,
sheet, granules), and the most prominent hazards (Roth et al., 2019).
The six types of 3D printing processes included material extrusion, vat
photopolymerization, powder bed fusion, binder jetting, material
jetting, and sheet lamination (Roth et al., 2019). Across the types of 3D
printing processes, the most common hazard was inhalation exposure,
followed by dermal exposure (Roth et al., 2019).
Our in review of 3D printing, we focused on feedstock material
categories, rather than the type of printing process, as more rather than
the type of printing process, information was readily available on
feedstock. There are four main types of materials used to “print” a
specific 3D-design. Categories include polymers, such as plastics, sup­
port materials for the creation of empty space, metals, and biological
materials (UVM, 2020). Each category has its own hazards. With plastics
and polymers, the potential for creating aerosolized nanomaterials exists
and has been the most characterized source of nanomaterials emitted
from 3D printers. Support materials are defined as a materials that are
used to create empty spaces or support overhanging features during
printing that is then later removed (Rengier et al., 2010). Support ma­
terials in printing can include non-isocyanate polyurethanes, waxes, and
water soluble monomers and polymers that have a potential hazardous
risk during production and disposal (Ligon et al., 2017). The risk from
support materials is due to the use of mild acid rinses needed to remove
support materials (Ligon et al., 2017); however risk from support ma­
terials is not related to nanomaterial exposure. No literature was found
regarding the potential for nanomaterial release from support materials.
Metals can be used as feedstock as a nano-powder and are highly
reactive and potentially combustible (Clemson, 2020). Fine metal
powders, such as titanium and aluminum, are common materials used as
a feedstock (Clemson, 2020). Metal nanomaterial feedstocks typically
include powder and metal wire (Nycz et al., 2016; Sames et al., 2016;
Baumers et al., 2017; Dutta and Froes, 2017; Jabbari and Abrinia, 2017;
Murr and Johnson, 2017). Metal feedstocks are also available as liquid
nanomaterial suspensions (Ko et al., 2010). Metal feedstocks are often
preferred over plastic feedstocks for production of objects needing high
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Ecotoxicology and Environmental Safety 207 (2021) 111458
conductivity in electronics (Ko et al., 2010). Because of the physico­
chemical properties of metal nanomaterials, they can be melted at lower
temperatures compared to the counterpart bulk metal material (Ko
et al., 2010). Little information is available on the risk to worker health
and safety associated with metal nanomaterial feedstocks. However, fine
metals powders have the potential to spontaneously combust leading to
fire, and due to high heat processes, thermal injury can occur (Clemson,
2020). The inhalation of metal powders is another potential exposure
route (Clemson, 2020). Given that limited information is available on
adverse effects related to inhalation of fine metal powders such as
nanomaterials, for risk assessment, we reccomment that a conservative
assumption is used that assumes inhalation exposure to metal nano­
materials from feedstock has similar risks as PLA released
nanomaterials.
Finally, biological materials are another potential feedstock. Bio­
logical materials have not been thoroughly reviewed as a source of
nanomaterial release during 3D printing. Given that no literature is was
found that addresses nanomaterial release during the use of support
feedstocks or biological material feedstocks, no assumption can be made
on the potential exposure levels. Only one study was identified for un­
derstanding biological feedstocks. Cellulose nanomaterials are not spe­
cifically used in additive manufacturing, but inhalation exposure is
possible due to their use in occupational settings in cement
manufacturing, automotive composites, packaging, and coatings (Ede
et al., 2019). Current research suggests that short-term exposure leads to
transient inflammation (Ede et al., 2019). This study is worth
mentioning because cellulose nanomaterials are bio-based (Ede et al.,
2019) and therefore may serve as a surrogate for understanding other
biological materials used in additive manufacturing.
The creation of polymer-based nanomaterials as a by-product of the
3D printing process have potential human exposure relating to inhala­
tion and dermal contact to nanomaterials, and corresponding human
health risks. Two main human exposure scenarios are associated with
nanomaterials produced from 3D printing: 1) inhalation exposure to
particles and 2) dermal exposure to particles. These two exposure sce­
narios are discussed below.
2.1.1. Inhalation
Inhalation of nanomaterials can occur during the formation of
nanomaterial by-products during the 3D printing process. However,
exposures to these nanomaterials and other consumables during the 3D
printing process (e.g., metal powders, solvents, isocyanate containing
compounds, etc.) are not well characterized. In general, potential
exposure during 3D printing has not been studied. Research has shown
that inhalation of nanomaterials may have detrimental health effects
(HSE, 2017; NIOSH, 2009; WHO, 2017; Praphawatvet et al., 2020). For
3D printers using a continuous stream of a plastic feedstock material, the
two most common forms of feedstock are acrylonitrile butadiene styrene
(ABS) and polylactic acid (PLA), a thermoplastic aliphatic polyester
(UVM, 2020). Health hazards depend on which plastic feedstock is used.
Both ABS and PLA plastic feedstocks release nanomaterials as by-
products during the 3D printing process (Kim et al., 2015; UVM,
2020). In general printer use, up to 68% of the aerosolized mass emitted
by printers are particles in the ultrafine particle (UFP) size range (<1
µm) (Zonteck et al., 2016).
Another study showed that all plastic feedstocks have the potential to
produce nanomaterials. Azimi et al. (2016) evaluated five types of
filament extrusion 3D printers in a small office environment with nine
different feedstocks for a total of 16 printer and feedstock combinations.
Some printers were partially enclosed to contain emitted particles as
part of the design. All 3D printers had an average of ~108 to 1011 par­
ticle counts/minute (Azimi et al., 2016), though peak particulate
emissions varied between printers and depended on the amount of time
the printer was in use. The potential for highest inhalation exposure
occurred with printers using ABS filaments, which had 2–9 × 1010
particles emitted/minute (Azimi et al., 2016).
A.A. Taylor et al.
Lowest exposure potential was associated in general with the PLA
filament printers which had ~108 particles emitted/minute; with the
make or model of the 3D PLA printer not an attributing factor in particle
count (Azimi et al., 2016). Printing different shaped objects was also not
a factor for particle count emissions, though different objects required
varying amounts of time to complete the printing process, which did
affect the UFP emission profile (Azimi et al., 2016). The bed tempera­
ture, or the temperature of the area holding the template and the liquid
feedstock reservoirs, did influence particle emission rates (Azimi et al.,
2016). 3D printer and feedstock combinations with the highest tem­
peratures had the highest emission rates (Azimi et al., 2016).
A similar study investigated PLA feedstock and particle release
(Stephens, 2013). PLA feedstock, when heated, releases up to 2 × 109
UFPs per minute, while ABS releases 2 × 1010 UFPs per minute (Ste­
phens, 2013). Particle sizes emitted during 3D printing depends on the
source material and the color of the material (NIOSH, 2016). For
printers using PLA feedstock, UFP concentrations were one to four times
higher compared to background levels, and particles in the 36–86 nm
size range had the largest increase when compared to background levels
(Stephens, 2013). Another study confirmed higher particle concentra­
tions emitted when using PLA compared to ABS (Kim et al., 2015). A
type of 3D printing called binder jetting printing builds a 3D design at a
rate of 25 mm/hour; therefore, total exposure time to emitted particles
may be over the course of hours (Afshar-Mohajer et al., 2015). Binder
jetting printing exceeded U.S. EPA ambient air quality standards with
the use of a central ventilation hood in the space (Afshar-Mohajer et al.,
2015). This was based on using exposure measured as a time weighted
average (TWA) over a 24-h period for particlulate matter with a 2.5-µm
size (PM2.5) and particulate matter with a 10-µm size (PM10) (Afshar-
Mohajer et al., 2015). Continuous operation exceeded standards by 10
times for PM2.5 and 3 times for PM10 (Afshar-Mohajer et al., 2015).
A study measuring nanomaterials emitted in real-time in four
workplaces showed peak concentrations of 140,000 particles/cm3 dur­
ing laser-cutting of boron-aluminum silicate glass and up to 20,000
particles/cm3 during generation of thin nanocarbon layers. In the same
study, during 3D printing using nanohydroxyapatite, up to 500 parti­
cles/cm3 were measured, and during chemical synthesis of silver
nanoparticles up to 35,000 particles/cm3 were measured (Oberbek
et al., 2019). These concentrations are approximately 105 orders of
magnitude lower than concentrations found in Azimi et al. (2016) and
Stephens (2013) studies, which were used in the above exposure
example. Though the concentrations described by Oberbek et al. (2019)
are not all specific to 3D printing, the range of nanomaterials detected
indicates that different processes and feedstocks will create varying
emission rates of nanomaterials. The study compared particles emitted
to the nano-reference values provided by the Dutch Social and Economic
Council, and recommended that safe levels should not exceed 20,000
particles/cm3 for nano-silver, and 40,000 particles/cm3 for carbon
black, nanohydroxyapatite and silica (Oberbek et al., 2019). Here, only
silver nanoparticles generated during chemical synthesis exceeded the
recommended value. Another study measured nanomaterials at six
commercial printing centers that utilize laser printing (Setyawati et al.,
2020). Though this data is not specific to 3D printing but rather general
printing practices, it serves as an example of occupational exposure to
nanomaterials. Nanomaterials such as titanium dioxide, iron oxide, and
silica were found in toners and as airborne particles (Setyawati et al.,
2020). Up to 500,000 particles/cm3 were detected during transient ex­
posures and up to 271–475 pmol/mg of polycyclic aromatic hydrocar­
bons were also detected (Setyawati et al., 2020).
Exposure to nanomaterials from feedstocks during 3D printing is also
a function of the number of printers in use and the size of the industrial
space containing the printers. In 2014, an industrial company was
anticipating a capacity for 60 3D printers using metal-based feedstocks
(Zelinski, 2014). Some assumptions on nanomaterial concentrations
released during 3D printing can be made based on nanomaterial release
measured during the use of PLA feedstock (Azimi et al., 2016). Assuming
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Ecotoxicology and Environmental Safety 207 (2021) 111458
the lowest value measured for emitted particles using various 3D
printers (108 particles/minute for PLA feedstock; Azimi et al., 2016),
and assuming the company was at a full production capacity of 60
printers simultaneously, 6 × 1010 particles/minute or approximately
~3 × 1013 particles for 60 machines would be emitted in an 8-hour work
day. If using the highest nanomaterial emission rate of 1011 from Azimi
et al. (2016), then up to ~3 × 1016 particles for 60 machines would be
emitted in an 8-hour work day. However, this assumption represents a
worse case scenario given that some printers realistically will be offline
and not emitting particles. This assumption also does not account for the
concentrations of particles found in the air, which would represent a
more realistic exposure concentration. Because minimal literature is
available on emitted particles and exposure levels, it is cautioned that
this estimate may not be realistic. Additionally, these expected exposure
levels may be very different from actual exposure levels given that
minimal information exists for 3D printing conditions found in a small
laboratory space versus an industrial setting. To date we know of no
studies that investigated the effects of different filtration or ventilation
systems in an industrial setting with 3D printers.
In general, the above studies all report the number of particles
emitted per minute for 3D printers, and do not accurately reflect the
exposure concentrations, or concentrations found in the air in the lab­
oratory space. To estimate worker exposure, air concentrations should
be measured in the breathing zone. Little information has been pub­
lished relating to air concentrations and realistic exposure to nano­
materials; however, NIOSH (2018) has shown that using 20 3D printers,
respirable particulate concentrations were found to be non-detectable,
or below 0.03 µg/m3 and volatile organic compounds (VOCs) were
below applicable occupational exposure limits (NIOSH 2018). The
amount of particulates emitted during 3D printing in the NIOSH (2018)
example are one to two orders of magnitude lower than the 8-hour time
weighted average (TWA) of 0.3 µg/m3 established for ultrafine titanium
dioxide (NIOSH, 2011c) and the 8-hour TWA of 1.0 µg/m3 for carbon
nanotubes (NIOSH, 2013). The Netherlands has developed a nano
reference value, similar to a TWA, that currently is used as a guide by
employers to protect worker health (Hendrikx and Broekhuizen, 2013).
The nano reference value for single- and multi- walled carbon nanotubes
is 10,000 particles/m3, and for numerous metal nanomaterials the nano
reference value is 0.02–0.04 particles/m3 (Hendrikx and Broekhuizen,
2013). These studies reflects a large range difference between particu­
late emissions (108–1011 particles/minute, Azimi et al., 2016) and par­
ticulate air concentration (0.3 µg/m3 (NIOSH, 2018) that should be
considered when determining realistic worker exposure. However,
while the potential for dilution of particles into airspace resulting in a
safe exposure may occur, both employers and workers should be aware
of symptoms relating to nanomaterial exposure.
Specific research on effects of inhalation exposure to nanomaterial
emissions from 3D printers is not available. The safety data sheet
accompanying the 3D printer used in the study by Afshar-Mohajer et al.
(2015) indicated that repeated or prolonged exposures to the printer
powder may cause coughing, eye irritation, sneezing, chest pain, and
lung diseases. In addition, research has shown that inhalation of nano­
materials has the potential to adversely affect health. For example, in a
7-hour laboratory study, rats showed inflammatory effects in the lungs
when exposed to 106 µg/m3 of the nanoparticulate carbon black (Gil­
mour et al., 2004). This concentration is an order of magnitude lower
than the exposure concentrations assumptions for the industry space
scenario presented above. Mice exposed to thermal decomposition
products during heating of ABS showed that ABS emitted particles were
more toxic and faster acting than three other types of polymer (Schaper
et al., 1994). An RD50, or the concentration causing a 50% decrease in
respiratory frequency, was set at 21.1 mg/m3. The recommended
exposure limit was estimated at 0.11 mg/m3 for ABS for the protection
of workers against irritating properties (Schaper et al., 1994). However,
combustion products were not characterized to determine type of par­
ticles emitted.
A.A. Taylor et al.
Adverse effects have also been observed in humans. Though not
specific to 3D printing, it has been documented that inhaled nano­
materials lead to inflammation of the lungs and mimic the same physi­
ological responses that lead to asthma attacks (Gustafsson, 2014;
Dobrovolskaia et al., 2017). A study conducted on particulate matter
found inside vehicles on motorways had an average of 24 µg/m3 of PM2.5
(Riediker et al., 2004). The study indicated that exposure to particulate
matter within vehicles impacted the health of young men and included
adverse effects such as inflammation, coagulation, and cardiovascular
effects.
One mechanism to reduce inhalation exposure is by using an
enclosure around the 3D printer. Zonteck et al. (2016) showed that more
particles are emitted from 3D printing as the printing temperature rises.
The distance from the printer also plays a large role in the amount of
particles to which a worker is potentially exposed. When an enclosure is
used to house the 3D printer, there was a 95% reduction in particles
measured in the air (Zonteck et al., 2016). However, another study
showed that the presence of an enclosure did not significantly affect
particle counts for ABS printers; only one printer had a 35% reduction in
particle emissions when an enclosure was used (Azimi et al., 2016). This
information indicates that there are still large data gaps for estimating
both exposure concentrations and understanding preventative measures
to reduce exposure.
2.1.2. Dermal
No specific literature is available for dermal exposures to nano­
materials from 3D printing. However, general dermal exposure to
nanomaterials has been investigated. For example, measured skin
permeation potential of nanomaterials is as follows: nanomaterials < 4
nm penetrate intact skin, nanomaterials in the range of 4–20 nm
potentially permeate damaged or intact skin, nanomaterials in the range
of 21–45 nm permeate only damaged skin, and nanomaterials > 45 nm
have no skin permeability (Filon et al., 2015). Assuming that some
fraction of nanomaterials in a given exposure may enter the skin, Hus­
sain et al. (2012) reviewed the current knowledge of nanomaterial in­
teractions with the immune system and other cellular responses. It was
found that nanomaterials can activate both the innate and active im­
mune responses (Hussain et al., 2012). Nanomaterial effects om the
immune system are wide ranging. For example, some nanomaterials
activate a pro-inflammatory response while others reduce the immune
cell response (Hussain et al., 2012).
General skin response to chemical exposures can be divided into
three categories: direct skin effects, immune-related effects, and sys­
temic effects (Andersen and Meade, 2014). Industrial exposure to
chemicals are more likely for chemicals that have a low molecular
weight and are both fat and water soluble (Andersen and Meade, 2014).
Direct skin effects include corrosion, necorsis, or irritation (Andersen
and Meade, 2014). For example, contact dermatitis, a direct skin effect,
makes up approximately 90–95% of occupational skin illnesses
(Andersen and Meade, 2014). Chemicals that cause an immune response
first cross the epithelial barrier and activate the innate or adaptive im­
mune responses (Andersen and Meade, 2014). However, for skin that
has been physically or chemically damaged, the passage of larger
chemicals such as inorganic metals or nanomaterials is possible
(Andersen and Meade, 2014; Tinkle et al., 2003; Kezic and Nielsen,
2009). Systemic effects are the least common type of reaction, and may
include acute poisonings, organ toxicity, carcinogenicity, and/or death
(Andersen and Meade, 2014). These general skin responses to chemicals
should also apply to nanomaterials. These general chemical exposures
may serve as a baseline for understanding nanomaterial exppsures.
Predicting the immune response based on nanomaterial properties is
difficult. It is especially challenging to predict the given amount of
nanomaterial by-products in the < 4–20 or 21–45-nm ranges produced
from 3D printing that would potentially enter intact or damaged skin
and cause an adverse effect. Making predictions on risks from dermal
exposure to nanomaterials from 3D printing is further challenging, as
5
Ecotoxicology and Environmental Safety 207 (2021) 111458
the potential exposure also depends on other physical-chemical char­
acteristics of the nanomaterials. For example, the likelihood of skin
permeability by nanomaterials can be decreased by creating liquid
suspensions of nanomaterials. Nanomaterials in liquid suspensions are
likely to undergo aggregation resulting in larger particle sizes that are
unlikely to permeate skin (Filon et al., 2015). Therefore, knowing the
nanomaterial form should be included in the exposure assessment.
Another challenge with understanding exposure to 3D printing ma­
terials is that other chemicals are found in the feedstocks. For example,
some of the components used in plastic printing are uncured chemicals
and are not nanomaterials. Some of the other chemicals used in 3D
printing have adverse effects, and are listed as irritants. For example,
components used in liquid suspensions include monomers that may
contain isocyanates, which are known sensitizers that may cause dermal
irritation (Ligon et al., 2017; Goossens et al., 2003). Therefore, adverse
effects may be caused by other components found in the feedstocks,
which are not directly related to nanomaterial exposure. To better es­
timate exposure potential to nanomaterials and other chemicals used in
3D printing, printer specifics such as the type of 3D printer, the feedstock
type with all components listed, the bed temperature, and the estimated
use (hours) of the printer need to be reported. Additionally, external
factors such as number of printers in use and ventilation of the work
space should also be considered when assessing exposure potential.
3. Regulation of ultra fine particles
There are no regulations for indoor UFPs. UFPs emitted during in­
door use of 3D printers can be up to 10 times higher than exposures to
UFP concentrations estimated during a typical 8-hour day at school,
~0.5 × 104 particles/m3 (Diapouli et al., 2007), UFPs in outdoor air
concentrations, 0.3 × 104 particles/m3 (Diapouli et al., 2007), or to UFP
concentrations within homes 0.0145 particles/m3 (Bhangar et al.,
2011). Compared to these UFP concentrations documented in other in­
door environments, nanomaterial concentrations estimated from 3D
printer use are in the range of 108–1011 particle counts/minute (Azimi
et al., 2016). Further research will become available in this field, espe­
cially information on exposure route and adverse effects, which will
likely influence the regulatory policies and management controls.
There are numerous nanomaterial regulations worldwide. For
example, a recent study evaluated 17 entities that have provided regu­
lations across three continents (Rodriguez-Ibarra et al., 2020). The study
found that guidelines or recommendations for nanomaterials are mostly
for metal oxide-based nanomaterials and that the amount (tonnage) of
nanomaterials produced is the main criteria used for registering nano­
materials (Rodriguez-Ibarra et al., 2020). Regulation of nanomaterials
includes evaluating and managing potential risks from the various
chemicals in products. As stated previously, nanotechnology is a
growing industry with increasing uses in medical devices, personal care
products, food, consumer products, pharmaceuticals, and industrial
applications (Hansen et al., 2009). As knowledge and applications of
nanomaterials continue to expand, the need for updated regulation
specific to nano-based industries is expanding.
Nano-based industries must follow evolving nano-related policies
and regulations. They will need to evaluate impacts of these regulations
to current and future products. Industry must review the following is­
sues: life-cycle analysis and supply chain knowledge of products,
detection of distinctive properties of materials, and estimation of
ecological and human toxicity and exposure potential. It is important to
identify industry-specific processes that result in direct exposure to
nanomaterials. A secondary exposure at industry facilities may be
through environmental site contamination caused from various 3D
printer processes. Both exposure paths may lead to direct or secondary
human exposure. Companies should proactively manage the changing
regulatory landscape and be involved in supporting regulatory author­
ities in improving policies and regulations. In North America and
Europe, the regulation and assessment of nanomaterial safety is based on
A.A. Taylor et al.
its intended use. The following section further summaries and discusses
industrial chemical regulation relating to nanomaterials in the United
States, Canada, and the European Union (EU).
3.1. Industrial chemical regulation of nanomaterials in the United States
Industrial chemicals in the United States are regulated by U.S. EPA
under TSCA. TSCA regulations are evolving and further action for nano-
form chemicals listed on the TSCA Inventory may be subject to reporting
and possible additional risk evaluation.
For purposes of regulation under TSCA, a chemical needs to be
included on the TSCA Inventory to be considered an “existing” chemical
substance in United States commerce (unless exempted from TSCA). Any
chemical that is not included in the TSCA Inventory is considered a “new
chemical substance.” The TSCA regulation was amended in 2016 and
now requires an affirmative statement of risk assessment. The law sets
forth five possible determinations under Section 5 for the risk of injury to
health or the environment with related actions: “(1) use is not likely to
present an unreasonable risk; (2) the substance is or will be produced in
substantial quantities and either enters or may enter the environment in
substantial quantities or there is or may be significant or substantial
exposure to the substance; (3) in the absence of sufficient information,
the manufacture, processing, distribution in commerce, use or disposal
of the chemical may present an unreasonable risk; (4) available infor­
mation is insufficient to allow the Agency to make a reasoned evaluation
of the health and environmental effects, or (5) use presents an unrea­
sonable risk” (U.S. EPA, 2018). If the U.S. EPA determines there is no
risk, the chemical can be listed on the TSCA Inventory and used for any
TSCA regulated product. If the risk can be managed with appropriate
controls, then the chemical will be listed with specific restrictions on
uses and handlings. If there is not enough information for the U.S. EPA to
make a determination, U.S. EPA will require additional testings, or if the
risk cannot be managed, U.S. EPA will not register the chemical for the
specific use.
Until recently, industrial chemicals and consumer products that use
nanomaterial versions of existing chemicals listed on the TSCA In­
ventory were not subject to any further review. If the bulk form of the
chemical was listed on the TSCA Inventory, then the nanomaterial
version of the same chemical could be imported or manufactured in the
United States for use in any industrial or consumer product. However, in
2008, TSCA issued guidance for determining whether a nanoscale sub­
stance is a “new” chemical only for the purposes of the TSCA Inventory
based on its molecular identity compared to that of its non-nano version
(U.S. EPA, 2008).
The U.S. EPA under TSCA has issued nanomaterial reporting rules (U.
S. EPA, 2017a) as well as significant new use restrictions (SNURs) for
existing chemicals. The nanomaterial reporting rule (U.S. EPA, 2017a)
affects companies that manufacture, import, or process chemical sub­
stances at the nanoscale, requiring one-time reporting of chemical
identity, production volume, methods of manufacture and processing,
use, exposure and release information, available health and safety in­
formation, and keeping records of this information (U.S. EPA, 2017a).
The information allows the U.S. EPA to evaluate the existing uses of the
nanomaterials and whether any further action is needed under TSCA,
including collection of additional information (U.S. EPA, 2017b). As
information on the hazard and exposure of nanomaterials evolves,
additional regulations will follow. Additionally, the U.S. EPA has final­
ized use restrictions via a significant new use rule for carbon nanotubes
(U.S. EPA, 2017c).
Further regulations regarding nanomaterials in the United States are
the OSHA Regulations and NIOSH Recommendations (Worker Protec­
tion Regulations). Currently, there are no legal occupational standards
in the United States to assess employee exposures to nanoparticles in the
workplace. OSHA regulates worker protection in the United States
(OSHA, 2013, 2017b). Under the hazard communication standard (29
CFR 1910.1200), workers must be provided with hazard information
6
Ecotoxicology and Environmental Safety 207 (2021) 111458
concerning the chemicals to which they are exposed, and workplace
training is required concerning these chemicals and hazards (OSHA,
2013, 2017b). This information is provided to workers through safety
data sheets (SDSs), product labels, and corporate hazard communication
training programs. The SDSs also provide information on exposure
limits, engineering controls, and recommended personal protective
equipment.
In the United States, OSHA regulations for classifying the hazards of
chemicals on SDSs and labels follows the United Nations Globally
Harmonized System (GHS) of Classification and Labelling (OSHA,
2009). As of 2020, nanomaterials under GHS have no specific hazard or
precautionary measure labeling (UNECE, no date; UN, 2016). Therefore,
SDSs do not always provide reliable information on nanomaterials
(WHO, 2017), and therefore, the responsibility for relaying information
regarding nanomaterials in products lies on information from chemical
suppliers or workplace managers where known nanomaterials are
handled.
As stated above, corporate hazard communication training programs
are a regulatory requirement under OSHA. According to The World
Health Organization (WHO), workers should be aware that the provided
SDS sheets do not always provide information on nanomaterials, such as
nanomaterials requiring specific engineering control measures, and
personal protective equipment that are not required for working with
the bulk form of the material, but may be required for working with the
nano-form (WHO, 2017). Few occupational exposure limits exist spe­
cifically for nanomaterials (OSHA, 2013). However, certain nano­
particles may be more hazardous than the bulk material of the same
substance. Therefore, existing occupational exposure limits for a bulk
substance may not provide adequate protection from the nanoparticle
form (OSHA, 2013). Future challenges will include setting guidelines for
risk exposure and accompanying endpoints and determining whether
these adverse effects are based on particle count or mass of the UFPs
emitted.
The National Institute for Occupational Safety and Health (NIOSH)
has published recommendations on exposure limits for various nano­
materials (NIOSH, 2011a, 2013). A recommended exposure limit for
carbon nanofibers and carbon nanotubes of 1 mg/m3 for the 8-hour TWA
was published by NIOSH (2013). For nanoscale particles of titanium
dioxide (TiO2), exposure limits should not exceed NIOSH’s 0.3 mg/m3
TWA concentrations for up to 10 h per day during a 40-hour workweek
(NIOSH, 2005). By contrast, NIOSH’s TWA for fine-sized TiO2 (particle
size greater than 100 nm) is 2.4 mg/m3 (NIOSH, 2011a). These rec­
ommendations are based on using chronic inhalation studies in rats to
predict lung tumor risks in humans (NIOSH, 2011a). Generally, existing
regulations in North America and Europe are being updated to cover
nanomaterials, but exposure to nanomaterials via 3D printing is
currently not clearly regulated except for some worker guidelines for
UFP exposure. Table 1 discusses various nanomaterial regulations found
in the US, Canada, and the European Union.
3.2. Canadian regulation of nanomaterials
Canada uses existing legislative and regulatory frameworks to miti­
gate the potential health risks of nanomaterials and to help realize their
health benefits. Health Canada has a policy statement that describes the
working definition of nanomaterials and elaborates on its objectives,
scope, and application (see Table 1 below; Health Canada, 2017a). One
of Health Canada’s main objectives is to gather information and estab­
lish internal inventories regarding regulated substances, products, and
any component material, ingredient, device, or structure that could be
considered a nanomaterial (Health Canada, 2017b). In addition, the
working nanomaterial definition is set up within the existing regulatory
frameworks that allow for information collection. One of the mandatory
requirements for nanomaterials suppliers falls under the Workplace
Hazardous Materials Information System (WHMIS). This is Canada’s
national hazard communication standard for workplace chemicals,
A.A. Taylor et al. Ecotoxicology and Environmental Safety 207 (2021) 111458

Table 1 Table 1 (continued )

Specific regulations and requirements for nanomaterials and products contain­ Country Type of substance Data to be Requested / Reference
ing nanomaterials in the United States, Canada, and Europe. Required by
Country Type of substance Data to be Requested / Reference Governing Agency
Required by produced, imported, • Particle size and
Governing Agency or distributed method used
United Reporting and EPA requires: U.S. EPA (2017a, • Particle size
States recordkeeping of new • Chemical identify 2017d) distribution and
and existing • Production volume method used
nanomaterials • Manufacturing • Aggregation
methods • Shape
• Processing, • Coating
expopsure, use, • REACH registration
release information number
• Available health and • Impurities
safety data • Surface area and
Canada Registration of any Health Canada may Health Canada charge
manufactured request following data (2017a, 2017b) Sweden Reporting of products KEMI requires: Swedish
substance or product when relevant: to which • Classification per CLP Chemicals
and any component • Intended use / nanomaterials have regulation 1272/ Agency (KEMI)
material, ingredient, function / purpose been intentionally 2008 2018
device, or structure at • Manufacturing • Function
or within the methods • Particle size
nanoscale in at least • Characteristics and • Form
one external physical chemical • Crystalline state
dimension properties • Surface area and
• Toxicological data charge
• Risk assessment and • Coating
risk management • Aggregation
REACH Registration of REACH requires: EC (2020) Norway Registration of EA requires: Norwegian
nanomaterials if • Characterization ECHA (2020) substance in nano- • Commercial name Environment
manufactured or (Annex VI) Gottardo et al. form if 100 kg or more • Hazard labelling Agency, 2020
imported at ≥ 1 • Chemical safety (2017), Paula of the product are information under
metric ton per year assessment (Annex I) et al. (2018) imported or CLP regulation
• Registration manufactured per • Name of Norwegian
information year customers
requirements • Chemical
(Annexes III and VII- composition
XI) • If a biocide, all
• Downstream user constituents must be
obligations (Annex identified
XII) • Explosives precursors
BPR Registration of BPR requires: ECHA (2012) listed if applicable
biocidal products • Dossier with data • Area of use and
containing requirements product type
nanomaterials • Risk assessment • Physical properties
• Nano “labeling”
• Monitoring and
reporting implemented through interlocking federal, provincial, and territorial
Belgium Reporting of FPS requires product Belgium Federal legislation. Legislation and related regulations establish classification
substances produced Registration, which Public Service criteria and set requirements for both labelling of workplace products,
in nanoparticular includes: (FPS) (2015,
states and mixtures • Chemical identify 2016)
including nanomaterials, and for related SDSs that provide information
containing such • Shape and size on the health and safety measures workers need to protect themselves
substances • Agglomeration data (Health Canada, 2017c).
• Coating
• Impurities
• Crystallographic 3.3. European regulations of nanomaterials
phases
• Surface area and
charge In Europe, nanomaterials are regulated as chemicals (depending on
• Quantity tonnage) or biocides when produced and applied in industries such as
• Use 3D printing. These industries are regulated by the European Chemicals
Denmark Reporting of mixtures EPA Requires: Danish EPA
Agency (ECHA), under the Registration, Evaluation, Authorisation and
and products that • Product registrations (2014)
contain nanomaterials • Amount produced Restriction of Chemicals (REACH) and the biocidal products regulation
(per REACH) (BPR). The European Union regulatory framework covers nanomaterials
• Identify and explicitly or implicitly (Rauscher et al., 2017) and the definition of
composition nanomaterials follows European Commission recommendation 2011/
• Particle size
• Surface chemistry
696/EU (EC, 2011). For REACH, most information requirements are
and size triggered by the tonnage in which the chemical is manufactured or
France Reporting of ANSES requires: ANSES (2012, imported (ECHA, 2017c; Rauscher et al., 2017). The REACH guidance
substances with • Identification 2017) includes requirements for registration of nanomaterials, with recent
nanoparticle status if • Physical state
updates, including specified information requirements for physico-
minimum quantity of • Commercial name
100 g/year has been chemical properties, toxicology, and registration information re­
quirements and downstream user obligations (ECHA, 2017c). Further
amendments are expected (EC, 2018; EUON, 2018). For biocides, the

7
A.A. Taylor et al.
BPR states that the approval of an active substance does not cover
nanomaterials except where explicitly mentioned and that the risk
should be separately assessed (Regulation [EU] No. 528/2012).
Furthermore, products containing nanomaterials are excluded from the
simplified authorization procedure, and the product label should state
that the product contains nanomaterials (Rauscher et al., 2017; Regu­
lation [EU] No. 528/2012). However, specific guidance is not available
for biocides. Another EU effort in the nano field includes the European
Union Observatory for Nanomaterials (EUON, 2018), which was
launched by ECHA and funded by the EC. The website provides infor­
mation about the uses, regulation, safety, research, and innovation of
nanomaterials (EUON, 2018).
Although European agencies are increasing their activities in the
nanomaterial area, a compulsory EU register for nanomaterials is not
envisaged (Rauscher et al., 2017). Various EU Member States, including
France, Denmark, Belgium, and Sweden, are concerned about the safety
of nanomaterials and have introduced their own solutions for gathering
information regarding how nanomaterials are produced, distributed, or
imported in their countries (see Table 1 below and ChemSafetyPRO,
2017; Rauscher et al., 2017). The registration is for specific compounds
and products. In Belgium, substances deliberately manufactured in
nanoparticular states and mixtures (such as paints and sunscreen) have
to be registered (FPS, 2016). There is no obligation to register for certain
product types, including biocides, medicinal products, foodstuff, animal
feed, pigments, and technological aid or other products that may be used
for processing ingredients of agricultural origin placed on the market in
a mixture, an article, or a complex object. The Danish inventory for
nanoproducts is intended to cover mixtures and products that contain
nanomaterials which are intentionally manufactured and are not
covered by other regulations (Danish EPA, 2014). Hence, manufacturers
and importers of foodstuffs and food contact materials, animal feed,
medicinal devices, medical products, cosmetics, pesticides, and waste
that may contain nanomaterials are not obliged to register their prod­
ucts. Rubber products, naturally occurring nanomaterials, biomolecules
and specific other products which contain nanopigments (e.g., certain
paint, fillers, textiles, and printing ink) are also exempt from reporting.
France requires declarations for intentionally manufactured substances
at nanoscale, on their own or contained in a mixture from which they are
likely to be released or extracted or in a material intended to reject such
a substance under normal or reasonably foreseeable conditions of use
(ANSES, 2017). Companies producing, distributing and importing these
substances have to register, if the minimum quantity of substance at
nanoscale during the year is 100 g. The Swedish Chemicals Agency
(KEMI) has implemented regulation that requires industries to report
any nanomaterial information when used in chemical products (KEMI,
2018). This information will be included in the Swedish products reg­
ister beginning February 2019 (KEMI, 2018; SAFENANO, 2017). The
proposal covers products to which nanomaterials have been intention­
ally added, regardless of concentration. Exemptions are made for
products from companies with an annual turnover of less than 5 million
Swedish crowns or if the nanomaterial is a pigment. For these exemp­
tions it will be sufficient to state that the nanomaterial is included in the
product (KEMI, 2018). Norway, while not an EU member state but an
European Economic Area (EEA) country, generally follows the EU
chemical legislation and the EC recommendation on nanomaterials. In
Norway, information on substances in nano-form is requested for
chemicals imported or manufactured at 100 kg or more per year (Nor­
wegian Environment Agency, 2020).
4. Ensuring safe new uses and product stewardship
For industries that produce, distribute, and/or import nanomaterials
within the United States, Canada and European countries, the existing
guidance in these countries covers nanomaterials. Even though regula­
tions on nanomaterial use in products are being implemented, exposure
to nanomaterials via 3D printing is currently not clearly regulated
8
Ecotoxicology and Environmental Safety 207 (2021) 111458
except for some worker guidelines for UFP exposure (OSHA, 2013).
While chemical regulations continue to catch up with technology,
maintaining safe uses is a global priority. In addition to existing regu­
lations, product stewardship efforts of companies can also ensure the
safety of workers, consumers, and the environment when working with
nanomaterials. NIOSH recommends limiting worker exposures to
nanoparticles through standard industrial hygiene practices, which in­
cludes properly ventilating work areas and choosing low-emitting
printers and feedstock materials (2016). Additional recommendations
by NIOSH include to use the manufacturer’s supplied controls and
maintain distance between the worker and the printer, and following
information on respiratory protection for workers handling nano­
particles (NIOSH, 2011b, 2016) and information on managing health
and safety associated with nanomaterials (NIOSH, 2009).
The Japan Society for Occupational Health has recommended three
approaches to controlling exposure: 1) control the emission and/or
dispersion of nanomaterials using engineering controls, 2) reduce
exposure by using personal protective equipment (PPE), and 3) provide
health examinations to workers and provide countermeasures based on
results (Suganuma et al., 2018). Examples of engineering controls
include using containment areas, automation, and exhaust ventilation
(Suganuma et al., 2018). Recommended cleanup for nanomaterials
suggests the use of wet wiping materials or cleaners with high efficiency
particulate air (HEPA) filters (Suganuma et al., 2018). PPE includes
respirators, gloves, and other protective clothing (Suganuma et al.,
2018). Respirators with a high assigned protection factor (APF) such as a
full respirator (APF 100) of a half-face respirator (APF 50) are recom­
mended (Suganuma et al., 2018). Finally, the Japan Society of Occu­
pational Health also suggests monitoring the workplace, though at this
time the allowable concentration of nanomaterials in the air has not
been determined (Suganuma et al., 2018).
Though not specific to nanomaterials used in 3D printing, a recent
study has shown that nanomaterial-containing consumer products have
increased from 54 in 2005 to 1827 in 2018, with many of these products
being consumer spray products that have the potential for aerosolized
nanomaterial exposure (Park et al., 2018). The study reviewed the
methods that are used for determining nanomaterial concentrations
found in aerosols and in products, and found that no standard methods
are available for evaluating consumer exposure to nanomaterial-based
products (Park et al., 2018). However, some models are being used to
estimate inhalation exposure and can be used to estimate exposure
associated with consumer products (Park et al., 2018). In general, more
work is needed for testing nanomaterial exposures. Specifically, con­
cerns exist for accurate testing of nanomaterials in the workplace. For
example, guidelines and methods for detecting particles in the nm range,
the ability to differentiate between ambient levels and nanomaterials
produced during additive manufacturing, and limitations on reference
of standard materials needed for testing. It is also recommended that
testing occur near the breathing space of the worker to determine an
accurate occupational exposure (Ghobadi et al., 2020).
Additional considerations for developing safe use of 3D printers in­
cludes an emergency response and spill cleanup plan, choosing appro­
priate personal protective equipment, appropriate waste disposal
methods, protocols for printer installation and maintenance, general
safety recommendations, potential printing hazards (CMU, no date), the
designated amount of air changes per the working space in an hour, and
use of a dedicated exhaust system. Instituting these types of measures in
a manufacturing setting will improve the safety of workers. Addition­
ally, guidelines for conducting comprehensive product stewardship
evaluations, including the exposure assessment process, are readily
available in the literature and can be applied to the nano-industry
(AIHA, 2018; Gottardo et al., 2017; Paula et al., 2018; EC, 2020;
Fadell et al., 2018; Spinazze et al., 2019; Landsiedel et al., 2017) It can
be concluded that using protective measures and standard operating
procedures that are already in-place for inhalation exposures in the
workplace also protect workers from nanomaterials. This provides some
A.A. Taylor et al.
evidence on why nanomaterial risk assessments and regulations have
been slowly implemented during the last decade. However, government
regulatory agencies need to clarify that current practices for protection
against inhalation of UFPs is also protective against nanomaterials.
Written enforcement of these practices in workplaces with nanomaterial
inhalation exposure is still necessary.
5. Conclusions
For product stewardship assessments, companies should better un­
derstand the products and manufacturing processes used in 3D printing,
the 3D printer specifications, and product lifecycles. This proactive
method helps companies prepare for forthcoming regulations for
nanomaterials and the potential for added expenses associated if addi­
tional data is requested through new regulations. An important part of
the product stewardship assessment is to understand routes of exposure
to nanomaterials, how nanomaterials are taken up into the body, and the
ways in which nanomaterials interact with biological systems in the
body. In this article an example for 3D printing was presented, focusing
on the 3D printing processes using nanomaterial feedstocks, and the
corresponding potential human exposure and human health risks. Two
main exposure scenarios were identified: inhalation exposure and
dermal exposure. Specific research on adverse effects of exposure to
nanomaterial emissions from 3D printers is not available. To address
potential human exposure and hazards, data on emissions from 3D
printing and effects from inhalation exposure to UFP and general dermal
exposure to nanomaterials were presented. The exposure and risk
analysis has many uncertainties given the lack of exposure data for
nanomaterials emitted from 3D printers.
It should be anticipated that more regulations on nanomaterials will
continue to be endorsed in the United States and globally. Regulations
may be specific to certain materials or specific shapes and sizes. More­
over, with the nanomaterials industry developing worldwide and across
many markets, fabricators, processors, and manufacturers will need to
be well informed on regulations on importing and exporting nano­
materials. Specifically, explicit requirements for nanomaterial infor­
mation may be imposed on international shipment by importing or
exporting countries. As standardized nomenclature and testing continue
to emerge, future regulations of nanomaterials will follow.
Further documentation and reporting can now be requested through
international regulatory authorities. Additional documentation will be
used to improve the understanding of the variety of nanoscale materials
in commerce, the function and application of those nanoscale materials,
and the potential exposure and toxicity to humans and the environment.
Additional regulations are likely once the regulatory agencies compre­
hend the nanomaterial industry. Proactive activities, such as open
communication with federal regulatory agencies on behalf of industry,
need to occur before and during the planning and application of regu­
lations. Such communication and collaboration between industry and
government are necessary to optimize the success of these new regula­
tions to ensure they are both protective and practical to enforce. Keeping
abreast of emerging international guidance and regulations and the
application of good product stewardship and disposal practices for
nanomaterials and products containing nanomaterials will promote the
safe use of nanomaterials as well as the protection of human and envi­
ronmental health. Industrial uses of nanomaterials are evolving as
knowledge of exposure potential grows; understanding co-evolving
regulations and their implications will be crucial for industry and spe­
cifically for risk practitioners.
CRediT authorship contribution statement
A.A. Taylor – Conceptualization, methodology, literature review,
majority of writing, reviewing, and editing, general idea for graphical
abstract. E.L. Freeman – Conceptualization, methodology, literature
review, writing, reviewing, and editing. M.J.C. van der Ploeg -
9
Ecotoxicology and Environmental Safety 207 (2021) 111458
Methodology, literature review, writing, reviewing, and editing.
Declaration of Competing Interest
The authors declare that they have no known competing financial
interests or personal relationships that could have appeared to influence
the work reported in this paper.
Acknowledgements
We would like to thank Eric Markowsky, Michael Posson, and Wil­
liam L. Goodfellow for reviewing the manuscript and providing
feedback.
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