Hazard study

In risk assessment, exposure is to be compared with some level of hazard level, usually a level that is considered ‘safe’. Such a hazard level is oftentimes derived from inhalation studies in rat and is usually expressed in terms of an amount that is inhaled (e.g. may be inhaled daily per kilogram body weight without expected detrimental consequences). For purposes of risk assessment it may be informative to compare doses from a hazard study in animals in terms of the alveloar load, as this is expected to be the most relevant end point for many materials.

To this end, ConsExpo nano enables the simulation of the alveolar load in hazard study conducted in the rat. The user may specify the dosing (air concentration, number of days of exposure, duration of the daily exposure) in combination with the material (aerosol size, nano material’s shape size and density). ConsExpo nano then estimates the alveolar load combining the estimated inhaled amount with a deposition and clearance model.

Deposition in the rat

The deposition fraction of the inhaled aerosol should be specified by the user. To estimate deposition fractions, the use can be made of the Multi-Pathway Particle Deposition (MPPD) model (MPPD).

Clearance of material from the rat alveoli is modelled using a clearance model proposed in the MPPD model (MPPD), based on data from a study by (Bermudez et al., 2004).

In this model, clearance is assumed to be load dependent: it decreases with increasing load, reflecting the fact that at high loads, alveolar clearance becomes increasingly impaired.

In ConsExpo nano, clearance (removal) of deposited mass m from the alveoli, is determined by a clearance rate kcl as

dm/dt=-kcl ×m

With the (load dependent) clearance rate kd (day-1)

kd= 0.03341×exp⁡(-1.7759 ×m0.3123)+0.00072

The alveolar load (in mass) is determined by combining the exposure events during the exposure period with the clearance. In the tool, the alveolar load is evaluated by numerically solving the equations for repeated dosing and clearance.