Estimates of carbon nanotube deposition in the lung: improving quality and robustness

Figures & data

Table 1. Characteristics of CNT aerosols sampled in various exposure situations.

Reference	Activity	CNT type	CNT observed in air samples?	Particle Characteristics
Maynard et al. (2004)	Removing CNT from production vessel	Laser ablated SWCNT,	Yes	Large, open agglomerates, 100 μm–1 mm in diameter (‘broadly-spherical’)
		HiPCO SWCNT	Yes	Large, open agglomerates, a few μm in diameter (‘broadly-spherical’)
Han et al. (2008)	Recovering CNT and blending composites	MWCNT	Yes	Individual and lightly agglomerated tubes, average diameter 55 nm, average length 1.5 μm (‘fiber-like’), and larger agglomerates, 100–300 nm and a few μm in diameter (‘broadly-spherical’)
Bello et al. (2010)	Drilling of CNT composites	MWCNT composites	Only during drilling	Particle clusters containing CNT aggregates a few μm in diameter (‘broadly-spherical’)
Lee et al. (2010)	Various (6 separate facilities)	MWCNT	During CVD production with no controls	Agglomerates of fibers, diameter ∼50 nm , length 3 μm (‘fiber-like’), and spherical particles, diameter 100–600 nm (‘broadly-spherical’)
Johnson et al. (2010)	Weighing, transferring to liquid and ultra-sonication	Raw MWCNT	Only during transferring	Loose bundles of tubes ∼ 500 nm in diameter (‘broadly-spherical’)
		Hydroxylated MWCNT	Only during sonication	Highly agglomerated bundles >1 μm in diameter (‘broadly-spherical’)
Dahm et al. (2012, 2015, 2018)	Various (14 separate facilities)	SWCNT, MWCNT, CNF	Yes (except one site)	Some individual fibers at 3 sites (‘fiber-like’), but mostly agglomerate structures (‘broadly-spherical’) of size >2 µm (data from a subset of 7 locations)
Hedmer et al. (2014)	Production (arc-discharge) and purification/ functionalization of CNT	MWCNT	Yes (higher concentration for production tasks)	Individual CNT (‘fiber-like’) found in 21% of samples; large (>3 µm) agglomerates found in 59% of samples
Kuijpers et al. (2016)	Synthesis, handling, research and office work	MWCNT	Yes (especially for synthesis and handling but also in office)	Mainly MWCNT agglomerates 0.5–10 µm (‘broadly-spherical’), no single fibers observed
Kouassi et al. (2017)	Manufacturing, recovery/cleaning	SWCNT	Yes	Loosely agglomerated SWCNT (‘micrometre scale’), sometimes associated with carbon black agglomerates and metal catalyst, in 7 of 8 samples during recovery/cleaning.

Table 2. Predicted aerodynamic diameters (in μm) of spherical particles with diameters and densities in the ranges observed for ‘broadly-spherical’ CNT particles (details of derivation in Supplementary Information) (values in brackets are the ratio of physical to aerodynamic diameter).

Physical diameter, d (µm)	Density (g cm^−3)
	0.1	0.5	1.0
0.1	0.012 (8.1)	0.056 (1.79)	0.1 (1.0)
0.3	0.054 (5.5)	0.19 (1.57)	0.3 (1.0)
1	0.27 (3.7)	0.69 (1.46)	1.0 (1.0)
2	0.58 (3.4)	1.39 (1.44)	2.0 (1.0)
5	1.53 (3.3)	3.51 (1.42)	5.0 (1.0)
20	6.3 (3.2)	14.1 (1.42)	20 (1.0)
100	31.6 (3.2)	70.7 (1.41)	100 (1.0)

Table 3. Aerodynamic and diffusion diameters and expected deposition mechanism(s) for different groups of CNT and asbestos particles.

Properties	Particle type
	‘Broadly spherical’ CNT	‘Fiber-like’ CNT (individual)	Asbestos
Aerodynamic diameter	Large range – 10 nm to 100 µm (Table 2) <Physical diameter	Primarily governed by fiber diameter ∼2.5–4 times fiber diameter Range 40–340 nm	Primarily governed by fiber diameter ∼3–5 times fiber diameter Range ∼300 nm to tens µm
Diffusion diameter	∼Volume equivalent diameter Large range 100 nm–100 µm	Dependent on both length and diameter Range 50 nm–1 µm	Dependent on both length and diameter Range ∼ 300 nm to several µm
Expected deposition mechanism(s)	Aerodynamic Interception (?) Diffusion (only for smallest particles)	Diffusion Interception (?) Aerodynamic (only for thickest fibers)	Aerodynamic Interception Diffusion (only for thinnest fibers)

Table 4. Recommended carbon nanotube aerosol characterization and suggested measurement methods for toxicity studies.

Parameter	Measurement method(s)	Derivation(s) from other measurements
Mass concentration (e.g. mg m^−3)	Filter sampling followed by ‘off-line’ gravimetric measurement ‘Online’ gravimetric instruments (e.g. Tapered Element Oscillating Microbalance, TEOM; Quartz Crystal Microbalance, QCM) Beta Attenuation Monitor, BAM	Derived from particle size distribution, ideally directly measured mass-weighted, or number-weighted along with density information Direct-reading optical instruments (e.g. DataRAM) along with suitable calibration for the material under test
Particle number concentration (e.g. # cm^−3)	Dedicated particle counter e.g. Condensation Particle Counter (CPC) Calculated from size distributions obtained via particle sizer e.g. Scanning Mobility Particle Sizer (SMPS), Aerodynamic Particle Sizer (APS)	Counting of particles from electron microscopy images
Surface area concentration^a (e.g. nm^2 cm^−^3)	Direct measurement via diffusion charging method e.g. Nanoparticle Surface Area Monitor (NSAM) Filter sampling of aerosolized material followed by gas adsorption method (e.g. LeBuf et al. 2011)	Derived from particle number- or mass-weighted size distribution and morphology information
Volume concentration^a (e.g. µm^3 cm^−^3)		Derived from mass concentration or aerosol mass size distribution and estimated particle density^d
Aerosol particle size distribution^b	Aerodynamic number size distribution: e.g. APS, Aerodynamic Aerosol Classifier (AAC) Mobility number size distribution: e.g. SMPS, ‘fast’ mobility particle sizers e.g. FMPS, DMS Aerodynamic mass size distribution: Size-segregated impaction-based methods e.g. Micro-Orifice Uniform Deposition Impactor (NanoMOUDI), Electrical Low Pressure Impactor (ELPI) followed by ‘off-line’ gravimetric measurement	Aerodynamic mass size distribution: Size-segregated impaction-based methods with real-time conversion e.g. Electrical Low Pressure Impactor (ELPI) (with assumed or otherwise measured density and shape factor correction) Optical Particle Counter (OPC) along with suitable conversion to the diameter definition of interest (e.g. aerodynamic or mobility diameter)
Particle morphology^c	Imaging (e.g. Transmission or Scanning Electron Microscopy, TEM/SEM)
Particle density^d (e.g. g cm^−3)	‘Tandem’ measurements with suitable instruments probing different aerosol properties e.g. aerodynamic followed by mobility classification (e.g. Aerodynamic Aerosol Classifier + Differential Mobility Analyzer, AAC + DMA) Selection of particles by e.g. mobility followed by mass measurement e.g. via TEOM, QCM	Derived from measurements and imaging (see text for discussion) Derived from measurements of at least two different diameter properties e.g. aerodynamic and mobility diameter across the particle size range (see text for discussion)
Distribution of particle morphology and density within various size fractions^a	Size-segregated impaction sampling followed by imaging e.g. sampling of size fractions using MOUDI with imaging of representative particles in each fraction
Additional toxicity related characteristics^a	e.g. rigidity (e.g. Kim et al. 2020), aerosol charge state (e.g. Kim et al. 2005)

^aParameters in italics are optional, beyond minimum requirements, to make studies more robust against developments in linkages between individual particle characteristics (e.g. fiber length/diameter and rigidity) and toxicity. Recommendations for measurements of ‘bulk’ characteristics of the material which may be important for toxicity (e.g. functionalization and/or chemical composition, zeta potential) but not specifically related to measurement of the aerosolized particles are not included in this table.

^bIdeally complete size distributions should be reported and relevant meta-data on instrument settings made available. For some purposes (for example for input into deposition models) parameterization of the size distribution (often assuming a log-normal distribution) is helpful, as a minimum reporting median and/or geometric mean diameter (typically aerodynamic or mobility, and number- or mass-based, depending on the measurement made) and geometric standard deviation.

^cDepending on form, parameters assessed may include fiber length, fiber diameter, aspect ratio, projected surface area, internal/external void space.

^dNote that different definitions of particle ‘effective density’ are used, see Supplementary Information.

Figure 1. Objectives and recommendations for future work to improve characterization of CNT aerosols, deposition modeling and dose estimation.

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