Table 4.
Sensitivity of results in dependence on modified input data (MPPD input parameters, steady state particle volume, clearance half time in humans) and different MPPD program versions: Estimated NOAEC in rats, calculated adaptation factors AF lung burden and AF clearance , and the derived human equivalent concentration (HEC) according to the second Model B procedure described by Equation (7) on p.182 and Equations (8), (9), (10) on p. 186 in [14]
| MPPD Version | MPPD input parameters* | Alveolar deposition fraction in rats /% | Alveolar deposition fraction in humans/% | Critical steady state particle volume burden/μL per kg-rat | Alveolar clearance half time in humans/days | NOAEC/mg/m 3 | AF lung burden /1 | AF clear ance /1 | HEC/mg/m 3 |
|---|---|---|---|---|---|---|---|---|---|
| 2.0 | IA switched off OMB | 7.5 | 16.4 | 1 | 400 | 0.53 | 0.93 | 0.93 | 0.53 |
| 2.0 | IA ONA | 6.3 | 8.4 | 1 | 400 | 0.63 | 1.52 | 0.93 | 1.03 |
| 2.11 | 3.3 | 8.8 | 1 | 400 | 1.21 | 0.76 | 0.93 | 0.98 | |
| 2.0 | IA ONA | 6.3 | 8.4 | 4.2 | 400 | 2.66 | 1.52 | 0.93 | 4.33 |
| 2.11 | 3.3 | 8.8 | 4.2 | 400 | 5.07 | 0.76 | 0.93 | 4.14 | |
| 2.0 | IA ONA | 6.3 | 8.4 | 1 | 250 | 0.63 | 1.52 | 0.58 | 1.65 |
| 2.11 | 3.3 | 8.8 | 1 | 250 | 1.21 | 0.76 | 0.58 | 1.58 | |
| 2.0 | IA ONA | 6.3 | 8.4 | 4.2 | 250 | 2.66 | 1.52 | 0.58 | 6.93 |
| 2.11 | 3.3 | 8.8 | 4.2 | 250 | 5.07 | 0.76 | 0.58 | 6.62 |
*IA, Inhalability Adjustment; OMB, Oronasal-Mouth Breather; ONA, Oronasal-Normal Augmenter; Other input data used invariantly and in accordance with [14] and [11]: reference body weights = 1 kg-rat, 70 kg-human; ventilation rates = 0.29 m3/kg-rat and day, 10 m3/70 kg-human and day; macrophage pool volumes = 7x1010 μm3/kg-rat and 50x1010 μm3/kg-human; alveolar clearance half time in rats = 60 days; MMAD = 1.8 μm, GSD = 2, density = 1 g/cm3 (particle characteristics); other MPPD input parameters as listed in the MAK document ([11], p. 57, 58 and Appendix).