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Arch Toxicol. 2019 Oct;93(10):2787-2796. doi: 10.1007/s00204-019-02561-z. Epub 2019 Sep 14.

Aluminium in plasma and tissues after intramuscular injection of adjuvanted human vaccines in rats.

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Paul-Ehrlich-Institut (Federal Institute for Vaccines and Biomedicines), Paul-Ehrlich-Straße 7, 63225, Langen, Germany.
Institute and Outpatient Clinic of Occupational, Social and Environmental Medicine, Friedrich-Alexander-Universität Erlangen-Nürnberg, Henkestrasse 9-11, 91054, Erlangen, Germany.
Preclinics GmbH, Wetzlarer Straße 20, 14482, Potsdam, Germany.
Paul-Ehrlich-Institut (Federal Institute for Vaccines and Biomedicines), Paul-Ehrlich-Straße 7, 63225, Langen, Germany.


Aluminium (Al) toxicokinetics after intramuscular (IM) injection of Al-adjuvanted vaccines is unknown. Since animal data are required for modeling and extrapolation, a rat study was conducted measuring Al in plasma and tissues after IM injection of either plain Al-hydroxide (pAH) or Al-phosphate (pAP) adjuvant (Al dose 1.25 mg), single human doses of three Al-adjuvanted vaccines (V1, V2, and V3; Al doses 0.5-0.82 mg), or vehicle (saline). A significant increase in Al plasma levels compared to controls was observed after pAP (AUC(0-80 d), mean ± SD: 2424 ± 496 vs. 1744 ± 508 µg/L*d). Percentage of Al dose released from injected muscle until day 80 was higher after pAP (66.9%) and AP-adjuvanted V3 (85.5%) than after pAH and AH-adjuvanted V1 (0 and 22.3%, resp.). Estimated absolute Al release was highest for pAP (836.8 µg per rat). Al concentration in humerus bone was increased in all groups, again strongest in the pAP group [3.35 ± 0.39 vs. 0.05 ± 0.06 µg/g wet weight (ww)]. Extrapolated amounts in whole skeleton corresponded to 5-12% of the released Al dose. Very low brain Al concentrations were observed in all groups (adjuvant group means 0.14-0.29 µg/g ww; control 0.13 ± 0.04 µg/g ww). The results demonstrate systemically available Al from marketed vaccines in rats being mainly detectable in bone. Al release appears to be faster from AP- than AH-adjuvants. Dose scaling to human adults suggests that increase of Al in plasma and tissues after single vaccinations will be indistinguishable from baseline levels.


Adjuvants; Aluminium; Intramuscular; Rats; Systemic availability; Vaccine


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