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Organ burden Sample Clauses

Organ burden. Within D 4.5, lung and olfactory bulb burden of rats following to 2 years inhalation of CeO2 nanoparticles (NM-212) is reported. There is a significant correlation between aerosol concentration and organ burden. In each dose group the organ burden was constantly increasing with time of exposure, although lung clearance is expected to occur likewise. However lung clearance was impaired in each dose group due to the CeO2 concentrations rising over the course of the exposure period. Thus overload is already to be expected if low doses (0.1 and 0.3 mg/m³) and mid doses (1 and 3 mg/m³) are inhaled chronically. Lowest and highest CeO2 amounts in lung were 78.22 μg and 4411.94 μg achieved after 24 months of inhalation of 0.3 g/m³ and 3 mg/m³ CeO2, respectively. Notably, the lung burden after 28 days of exposure to 25 mg/m³ (see deliverable 4.4) and 12 months to 3 mg/m³ was about the same. Calculation of the linear regression revealed a linear increase of lung burden in each dose group with a correlation of 0.999. While the influence of the dose is highly significant (p < 0.001), this is not the case for time. Also, investigation of the olfactory bulb showed increasing CeO2 concentrations over time in all dose groups. It is assumed, that nanoparticles are taken up by the nerve endings of the olfactory bulb from where they might be further translocated. Lowest and highest CeO2 amounts in olfactory bulb after 24 months of exposure were measured with 0.42 ng and 8.98 ng. The amounts of ceria detected in olfactory bulb are equivalent to 2.47*10-4 % of the corresponding lung burden. However, the data show a significant organ burden (p-value < 0.05) of olfactory bulb in all dose groups compared to the control. It is assumed that also secondary organs like lymph nodes, liver, spleen and kidney will show significant CeO2 concentrations compared to control groups. Out of the secondary organs, tracheobronchial and mediastinal lymph nodes are anticipated to possess highest amounts of CeO2 due to their lung draining functions. This was already shown by the results on organ burden within the 28 day study (OECD TG 412) performed previously. Furthermore, liver is expected to be a target organ for particle clearance due to its metabolic characteristics. Concerning excretion, low amounts of CeO2 are expected in urine while most of the material should be eliminated via faeces. Results on particle distribution and elimination will be reported in the next deliverable.

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