Translational toxicology in setting occupational exposure limits for dusts and hazard classification – a critical evaluation of a recent approach to translate dust overload findings from rats to humans

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	IA ONA	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	IA ONA	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	IA ONA	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	IA ONA	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).

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