Aluminum and aluminum oxide nanomaterials uptake after oral exposure - a comparative study
Link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7021764/
Sci Rep. 2020; 10: 2698. Published online 2020 Feb 14. doi: 10.1038/s41598-020-59710-z PMCID: PMC7021764 PMID: 32060369
Benjamin C. Krause,
#1 Fabian L. Kriegel,#1 Daniel Rosenkranz,#1 Nadine Dreiack,1 Jutta Tentschert,1 Harald Jungnickel,1 Pegah Jalili,2 Valerie Fessard,2 Peter Laux,1 and Andreas Luch1
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Abstract
The knowledge about a potential in vivo uptake and subsequent toxicological effects of aluminum (Al), especially in the nanoparticulate form, is still limited. This paper focuses on a three day oral gavage study with three different Al species in Sprague Dawley rats. The Al amount was investigated in major organs in order to determine the oral bioavailability and distribution. Al-containing nanoparticles (NMs composed of Al0 and aluminum oxide (Al2O3)) were administered at three different concentrations and soluble aluminum chloride (AlCl3·6H2O) was used as a reference control at one concentration. A microwave assisted acid digestion approach followed by inductively coupled plasma mass spectrometry (ICP-MS) analysis was developed to analyse the Al burden of individual organs. Special attention was paid on how the sample matrix affected the calibration procedure. After 3 days exposure, AlCl3·6H2O treated animals showed high Al levels in liver and intestine, while upon treatment with Al0 NMs significant amounts of Al were detected only in the latter. In contrast, following Al2O3 NMs treatment, Al was detected in all investigated organs with particular high concentrations in the spleen. A rapid absorption and systemic distribution of all three Al forms tested were found after 3-day oral exposure. The identified differences between Al0 and Al2O3 NMs point out that both, particle shape and surface composition could be key factors for Al biodistribution and accumulation.
Subject terms: Metals, Nanoparticles, Analytical chemistry
In conclusion, our in vivo study showed a significant uptake of Al from both, Al0 and Al2O3 NMs, following a 3-day oral gavage treatment. Rapid absorption and systemic distribution of Al for all three different forms tested is concluded. Nevertheless, some differences between Al0 and Al2O3 NMs were observed assuming that agglomerate shape and surface composition may play an important role in particle accumulation. In contrast to in vitro results from the literature Al2O3 NM accumulates to a higher extent in comparison to Al0 NM in both, intestine and systemic organs. Our findings identify challenges in the extrapolation of NM accumulation, even if the used materials possess a similar chemical composition. An interesting difference to ionic Al was the long retention time of Al levels in blood with Al2O3 NMs. The low dose study design challenged conventional ICP-MS approaches. In order to increase the sensitivity and robustness of the technique we conducted a matrix calibration in combination with a DRF, which showed superior performance in terms of sensitivity compared to the standard water calibration method. The applied method also eliminated the influence of day to day variation on the calibration. This method enabled the reliable quantification of all Al organ burdens even in the low µg/g range. Our study successfully showed that a respective matrix matched calibration can easily improve the data quality for the evaluation of low dose studies. The approach of statistical evaluation presented here utilizes a DRF to enable robust data analysis in order to obtain resilient data for risk assessment.
Conclusão:
Após 3 dias de exposição, os animais tratados com AlCl3 · 6H2O apresentaram altos níveis de Al no fígado e intestino, enquanto que após o tratamento com Al0 NMs, quantidades significativas de Al foram detectadas apenas neste último. Por outro lado, após o tratamento com Al2O3 NMs, o Al foi detectado em todos os órgãos investigados com concentrações particularmente elevadas no baço. Uma rápida absorção e distribuição sistêmica de todas as três formas de Al testadas foram encontradas após 3 dias de exposição oral.
