Figure 8
Kinetically simulated 4-week (left) and 13-week (right) OECD#412/413 [[8]-[10]] compliant inhalation studies on rats for estimation of the volume concentration required to attain a cumulative PSP-volume lung burden similar to the NOAEL and the MTD. Key is the selection of an intermediate concentration to demonstrate reversible lung-overload and associated adverse outcomes [4],[36] within the kinetically simulated post-exposure period. Simulations used volumetric concentrations of 0.25, 0.75, and 2.2 μl PSPresp/m3 for the 4-week study and of 0.11, 0.3, and 1.0 μl PSPresp/m3 for the 13-week study. The simulations rely upon the correct estimate of that MPPD-modeled respirability and agglomerate density achieved in the particular study under consideration (for details see [4],[6],[23]). Any faster reversibility than predicted would have suggested facilitated dissolution of PSP in the lung. In case all constraints of the 4-week inhalation study are fulfilled, the NOAEL and OEL/DNEL from longer exposure periods can be predicted. Adjustments for exposure durations (AF) have been detailed elsewhere [4],[5]. Modelling is not supported for substances where the predicted outcome of the 4-week study does not match the empirical outcome.