Refine
Has Fulltext
- no (46)
Year of publication
Document Type
- Other (46) (remove)
Is part of the Bibliography
- yes (46) (remove)
Keywords
- Absorption kinetics (1)
- Aerosol (1)
- Aluminium (1)
- Aluminium adjuvants (1)
- Haar system (1)
- In vitro dissolution (1)
- Raman lidar (1)
- Toxicokinetic modelling (1)
- inversion (1)
- particle microphysics (1)
Institute
- Institut für Mathematik (46) (remove)
As a potentially toxic agent on nervous system and bone, the safety of aluminium exposure from adjuvants in vaccines and subcutaneous immune therapy (SCIT) products has to be continuously reevaluated, especially regarding concomitant administrations. For this purpose, knowledge on absorption and disposition of aluminium in plasma and tissues is essential. Pharmacokinetic data after vaccination in humans, however, are not available, and for methodological and ethical reasons difficult to obtain. To overcome these limitations, we discuss the possibility of an in vitro-in silico approach combining a toxicokinetic model for aluminium disposition with biorelevant kinetic absorption parameters from adjuvants. We critically review available kinetic aluminium-26 data for model building and, on the basis of a reparameterized toxicokinetic model (Nolte et al., 2001), we identify main modelling gaps. The potential of in vitro dissolution experiments for the prediction of intramuscular absorption kinetics of aluminium after vaccination is explored. It becomes apparent that there is need for detailed in vitro dissolution and in vivo absorption data to establish an in vitro-in vivo correlation (IVIVC) for aluminium adjuvants. We conclude that a combination of new experimental data and further refinement of the Nolte model has the potential to fill a gap in aluminium risk assessment. (C) 2017 Elsevier Inc. All rights reserved.
S-test results for the USGS and RELM forecasts. The differences between the simulated log-likelihoods and the observed log-likelihood are labelled on the horizontal axes, with scaling adjustments for the 40year.retro experiment. The horizontal lines represent the confidence intervals, within the 0.05 significance level, for each forecast and experiment. If this range contains a log-likelihood difference of zero, the forecasted log-likelihoods are consistent with the observed, and the forecast passes the S-test (denoted by thin lines). If the minimum difference within this range does not contain zero, the forecast fails the S-test for that particular experiment, denoted by thick lines. Colours distinguish between experiments (see Table 2 for explanation of experiment durations). Due to anomalously large likelihood differences, S-test results for Wiemer-Schorlemmer.ALM during the 10year.retro and 40year.retro experiments are not displayed. The range of log-likelihoods for the Holliday-et-al.PI forecast is lower than for the other forecasts due to relatively homogeneous forecasted seismicity rates and use of a small fraction of the RELM testing region.