1. Modelling exposure to nanomaterials in spray product
The use of nanomaterials in spray products may lead to inhalation exposure of consumers to the nanomaterial. Of special concern is the potential deposition of nanomaterial in the pulmonary (alveolar) region. Poorly soluble material is only slowly cleared from this region. Alveolar deposition may lead to protracted local exposure and accumulation of the nanomaterial in the case of frequent exposure. The duration and magnitude of alveolar load of a nanomaterial has been identified as one of the primary determinants of local adverse effects such as inflammation in the lung. (Braakhuis et al, 2014)
ConsExpo nano is a tool that can be used to estimate inhalation exposure as the inhaled dose and the alveolar load of nanomaterials for consumers using spray products. The tool combines models for exposure, deposition and clearance to estimate alveolar load. The exposure is expressed in different dose metrics for quantitative risk assessment.
The user manual can be found here.
- Inhalation exposure and alveolar load of nanomaterials in spray products
- Nanomaterial exposure model
- Dose metrics
- Calculation of the dose metric
- Calculation of the dissolution
During use of a spray product, the nanomaterial is released and
may become airborne.
Nanomaterials will generally be released as part of aerosol particles. Aerosol particles carrying the nanomaterial may be inhaled and may deposit in various regions of the respiratory tract, in particular in the alveolar region. Deposited particulate material will be removed from the alveoli by clearance (e.g. macrophage and ciliary clearance), dissolution and interstitialisation. For poorly soluble nanomaterials, all these processes are expected to be slow.
The total alveolar load of a nanomaterial at any given time is the result of competing kinetic processes of (repeated) exposure, deposition and clearance.
The magnitude of the aerosol air concentration is determined by the spray and the conditions of its use. It is in particular a result of the mass generation rate of the spray, the size (distribution) and mass density of the generated aerosol, the duration of use of the spray, ventilation of the air et cetera.
Deposition of the inhaled aerosol in the respiratory tract will depend on both aerosol characteristics and human physiology. The most important aerosol characteristics the determine deposition are the aerosol (aerodynamic) diameter and its mass density. The critical aspects of human physiology are the geometry of the lung and the breathing pattern (i.e. intensity of breathing) of the exposed person.
To model exposure and the alveolar load, ConsExpo nano combines a number of models.
Alveolar load of an inhaled nanomaterial is the result of three distinct processes:
- Inhalation of aerosol particles containing the nanomaterial that have become airborne after the use of a spray product
- Deposition of the inhaled aerosol particles in the respiratory tract
- Clearance of the inhaled material from the alveoli by the pulmonary macrophage system and by dissolution of nanomaterial in the macrophages after phagocytosis
ConsExpo nano links four separate models to estimate time dependent alveolar load:
- A model to estimate the concentration and the inhaled mass of the sprayed aerosol
- A model to estimate the deposition in the alveoli based on the aerosol diameter and mass density
- A model to simulate clearance of the material from the alveoli, assuming non-soluble particle load in the alveoli
- A kinetic model that account for dissolution of the material using user-specified information on the dissolution rate of the material in the alveoli (e.g. in the macrophage or the lung lining fluid)
The model that simulates the external aerosol concentration in
indoor air is equivalent to the ConsExpo ‘exposure to spray model’.
A description of this model and the equations can be found in
(Delmaar et al. 2005).
The models used to simulate deposition and clearance from the alveoli is an implementation of the ICRP deposition model. (ICRP, 1994) gives model equations and values for the model parameters derived from inhalation and deposition experiments. The reference provides different parameter sets depending on age, gender and activity level. ConsExpo nano implements two models: the model for males and females performing light exercise.
Dissolving <link ‘dissolving: ’> of the nanomaterial is modelled by a first order kinetic process in which the user specifies a dissolution rate of the nanomaterial per day. Only relatively low dissolution rates will be accepted as input as the deposition and clearance models have been developed for poorly soluble aerosols.
In summary, ConsExpo nano estimates inhaled dose and alveolar load of a nanomaterial in spray particles. The following assumptions are made:
- the alveolar load varies in time and depends on the inhalation, deposition and clearance of particulate matter
- the nanomaterial is released as part of an aerosol. The nanomaterial is transported in the aerosol particles in indoor air and through the respiratory tract. I.e. the properties of the aerosol particle will ultimately determine inhalation and deposition of the nanomaterial
- the aerosol particles are assumed to consist of the nanomaterial only. No other components are assumed to be present
- the aerosol particles are assumed to remain unaltered in the process of inhalation and deposition. Only when deposited in the alveolar region, changes in aerosol due to dissolution (in lung lining fluid or alveolar macrophages) are considered
- Dissolution of the nanomaterial in the alveoli (either in macrophage or lung lining fluid) is considered as a first order kinetic process, characterised by a single, constant dissolution rate. This rate is to be specified by the user
In the risk assessment for regular (i.e. non-nano material)
substances, inhalation exposure is usually expressed on the basis
of the inhaled mass. The safety of the use of the substance is
assessed by comparing mass-based exposure estimates to levels of
inhaled mass that are believed not to lead to adverse health
For nanomaterials, it has been shown that similar mass doses of particles with different geometry may induce very different levels of effect in test animals. Therefore, mass does not seem to be an appropriate metric to base the risk characterisation on.
Different alternative dose measures have been suggested in literature, but consensus on a common metric, or whether such a metric is feasible at all, has not been achieved.
ConsExpo nano expresses the alveolar load in different, potentially relevant dose metrics.
The following dose metrics are included:
- the number of nanoparticles
- the total surface area of nanoparticles (mm¬2)
- the total mass of nanoparticles (mg)
- the total volume of the nanoparticles (mm3)
- the number of aerosol particles
- the total surface area of aerosol particles (mm2)
- the total volume of the aerosol particles (mm3)
These dose metrics are calculated from the particle properties provided by the model’s user, assuming that nanoparticles are adequately represented by simple geometric shapes (e.g. spheres, cylinders).
The exposure, deposition and clearance models express the output
in terms of the mass of the aerosol particles and the model
evaluation does not depend on the characteristics of the
nanomaterial. Consequently, the different dose metrics can be
calculated from the lung load expressed as mass of the deposited
aerosol particles M ap (g).
The aerosol particle is assumed to consist completely of nanoparticles, which means that no other components are included.
Dose metrics are calculated as:
- Mass nanomaterial:
- Number of nanoparticles:
- Total surface area nanoparticles:
The surface area of the individual particle is calculated from the specification of the nanomaterial geometry by the user. ConsExpo nano supports three particle geometries: sphere, cylinder and sheet. For these, the surface areas are calculated as:
ρnm : density nano material
vnp : volume nano particle
dnp : diameter nano particle
ρap : density aerosol particle
vap : volume aerosol particle
dap : diameter aerosol particle
hnp : height of a cylindrical nano particle
σnp : single sided surface area of a nanosheet
These calculations are based on the single valued (i.e. median)
When a distribution of aerosol particle diameters is considered, calculations change.
It is assumed here that particle diameter distributions PM (δ) are mass (or equivalently: volume) distributions, i.e. PM (δ)dδ gives the fraction of the total mass (volume) of the particles with diameter between δ and δ+dδ.
The relation between the normalized diameter distribution PM (δ) and the actual (non-normalized) diameter distribution P(δ) is given by
P(δ)=Map ×PM (δ)
When considering a distribution of the diameter of the aerosol particle, the dose metric calculations of the ‘surface area aerosol particle’ and ‘number of aerosol particles’ change to:
- surface area aerosol particles:
- number of aerosol particles:
Following inhalation and deposition in the alveoli, the
nanomaterial may dissolve and be removed. Dissolution may occur in
the lung-lining fluid, or after phagocytosis in the alveolar
macrophages. ConsExpo nano accounts for slow dissolution in the
alveoli. Dissolution is modeled using a user-specified dissolution
rate k (specified as a fraction of deposited mass dissolved per
unit of time).
The deposited mass Mdep will change in time due to dissolution according to a linear kinetics decay as:
Dose metrics other than the mass will be evaluated by assuming that the primary nanomaterial will not change due to dissolution, but only the diameter of the deposited aerosol will shrink according to
The various dose metrics are then re-evaluated by first calculating how many nano particles will fit in the aerosol particle of reduced size, and then repeating the dose calculations <link ‘calculations’: 1.4> for the different dose metrics with adjusted total mass and aerosol size distribution.
Hedwig M Braakhuis, Margriet VDZ Park, Ilse Gosens, Wim H De Jong and Flemming R Cassee
Physicochemical characteristics of nanomaterials that affect pulmonary inflammation. Particle and Fibre Toxicology 2014, 11:18
Delmaar, J.E., M.V.D.Z. Park, J.G.M. van Engelen, 2005. ConsExpo, Consumer Exposure and Uptake Models. Program Manuel. Bilthoven, The Netherlands: National Institute for Public Health and the Environment (RIVM). RIVM Report no. 320104004