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Figure 3 | Particle and Fibre Toxicology

Figure 3

From: Derivation of occupational exposure levels (OELs) of Low-toxicity isometric biopersistent particles: how can the kinetic lung overload paradigm be used for improved inhalation toxicity study design and OEL-derivation?

Figure 3

The dependent variables ‘elimination half-time’ (top left) and ‘influx of neutrophils (PMN) in BAL’ (bottom left) were analyzed relative to the independent variable ‘cumulative dose’ expressed as C respirable × Σt and both (in using an inhaled volume per exposure day this metric is proportional to the accumulated volumetric lung burden; for details see reference [[4]]). The illustration supports a normal range of elimination half-times of t1/2 = 60 – 90 days which precedes any influx of PMN (vertical arrow left). The maximum tolerated dose (MTD) was believed to be attained at t1/2 = 1 year (vertical arrow right). For any chronic 2-year inhalation study on rats these targeted cornerstones are met at exposure concentrations of 0.06 μL PSPresp/m3 (NOAEL) and 0.26 PSPresp/m3 (MTD). At these cumulative lung burdens the elimination half-times are expected to be t1/2 = 80 and 400 days, respectively. Of note is the increasing disparity of external exposure concentrations and cumulative lung burdens at MTD: a ~4-fold difference in exposure concentrations yielded a ~17-fold higher lung burden at MTD (right) (for more details see [4]).

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