TLRToll-like receptor agonists use in immunotherapy (e.g. MPL/CpG motifs) has shown some excellent benefits [64]. However, such adjuvants will not function as depot mediators. The physical adsorption of antigen onto the adjuvant and subsequent ‘slow-release’ of antigen is considered to be a very important mechanism, particularly in SCIT. In some products, the depot mediator – l-Tyrosine – is used in combination with MPL. Here, Tyrosine allows slow release of allergens. While find more MPL will drive an appropriate immunological response (Th1), thus enabling a unique ultra-short course therapy for the allergic patient [75]. In summary, the amount of aluminium applied in

SCIT will significantly contribute to a higher cumulative life dose. Unlike essential prophylactic vaccinations, numerous injections with higher proportions of aluminium-adjuvant per injection are applied in SCIT. Comparably high

amounts of aluminium are administered, particularly during long-term SCIT for hymenoptera venom allergies whilst there are aluminium-free products commercially available. Aluminium analysis is technologically click here demanding. The very low concentrations and possibility of contamination poses problems. Aluminium compounds are of biological significance—cf. above. The stability of these aluminium compounds constitutes an additional complicating factor in analysis. However, several methods are available: The atomic absorption

spectrometry (AAS), and particularly graphite furnace atomic absorption spectrometry (GF-AAS), are single element methods with detection thresholds of approximately 1 μg/L. This method is commonly applied for analysing biological samples and aqueous media. However, inductively coupled plasma–optical emission spectrometry (ICP-OES) now provides a more sensitive alternative, able to measure lower concentrations of the metal, especially when using quadrupol (ICP-qMS) or high-resolution sector field ICP-MS (ICP-sf-MS). These devices are however expensive and of limited availability. Table 3 summarises the type of analytical methods mentioned above, their detection range(s), strengths and limitations. The German Research Foundation (DFG) assembled an independent expert group entitled “Analyses in Biological Material”. This group has published research papers Calpain on threshold values and methods (MAK collection) and are able to advise on how to reasonably measure, e.g., the aluminium exposure caused by SCIT [77]. There is currently no generally accepted surrogate parameter which would reflect the cumulative burden to the body posed by aluminium [19]. In summary, aluminium analysis is expensive and highly demanding although the technology is available to detect trace amounts of the metal in biological samples. The DFG provides independent expertise with the work group “Analyses in biological material”.