Nanomaterial exposure model
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 accounts 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)
For the estimation of the inhalation exposure, two options are available to the user. First, the user may use the ‘spray scenario’. With this option, the tool uses the a model that simulates the external aerosol concentration in indoor air that 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). Alternatively, the user may specify a ‘custom scenario’. In this case the user gives the air concentration, aerosol particle size and exposure duration, from which inhalation exposure is estimated. This is done by assuming that the air concentration Cair is completely inhalable and thus the inhaled amount Ainh is determined as:
Where Qinh is the inhalation rate (volume per time) and T the exposure duration.
The models used to simulate deposition and clearance from the alveoli is an implementation of the ICRP deposition model. (ICRP, 1994; ICRP 2015) 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 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.