Long-term retention of injected aluminium-26

Abstract

Data previously reported on the whole-body retention of aluminium-26 ((26)Al) in a male volunteer are extended to 8 years after intravenous administration as citrate, when only ~2% of the injected tracer remained. The extended data, combined with a report elsewhere of the late urinary and faecal excretion of (26)Al by this subject, reinforce indications that transdermal losses contribute to the clearance of systemic aluminium and mitigate its long-term accumulation from chronic exposure.

Human exposure to aluminium

“…The blood is probably the main distribution network for systemic aluminium though this statement is made with the proviso that there are no reliable data on the aluminium content of lymph. There are data showing signicant concentrations of aluminium in sweat 50,51 and these suggest that the lymphatic system may have a role to play in aluminium transport throughout the body. Aluminium is found in blood associated with both serum and cell fractions.…”

“…87 Recent data for individuals presenting at a renal stones clinic suggest a median daily excretion of only 5 mg of aluminium 89 while our own results for 20 young and healthy individuals give a mean urinary excretion of aluminium of 27 mg per 24 h. 90 While urine has been considered as the major route of excretion of systemic aluminium there are intriguing new data on the aluminium content of sweat which implicate perspiration as an efficient and neglected mechanism of removal of aluminium from the body. 50,51 If sweat is a major route for the elimination of systemic aluminium then we may need to consider this in the light of our everyday use of antiperspirants. 91 As has been found for other areas of human physiology the data describing the excretion of aluminium from the body is incomplete and to the extent that any attempt to model human exposure to aluminium is likely to be premature.…”

Physiology-based toxicokinetic modelling of aluminium in rat and man

“…Furthermore, the estimated parameters were robust to changes in the initialisation of the estimation algorithm and randomness during generation of the training dataset. For all three validation datasets, our model precisely predicted the corresponding time-profiles, even for long time spans (Newton and Talbot 2012). While the retention dataset itself was not part of the training data, the same individuals, however, were included in the training dataset with plasma, blood, and urine samples.…”

“…This leads to the inclusion of the diploma thesis by Beck (1997) and the articles by Kobayashi et al (1990), Steinhausen et al (1996), Nolte et al (2001). Finally, we decided to exclude the studies on wholebody retention (Priest 2010;Newton and Talbot 2012;Talbot et al 1995), since these are less suited for PBTK model development, but may better be used for model validation.…”

“…This statistical framework allows us to rigorously differentiate between inter-individual/inter-study variability and uncertainty, and to propagate variability and uncertainty to the observation level for an assessment of model predictivity. After parameter estimation, the PBTK model was evaluated against different validation datasets, comprising recently obtained 27 Al plasma data in rats over 24 h (Weisser et al 2019), 26 Al full-body retention data in humans over 375 weeks (Newton and Talbot 2012), and recent 26 Al blood data in humans over 3 weeks (de Ligt et al 2018).…”