This data has been modelled to give an estimation of variation

This data has been modelled to give an estimation of variation Alisertib both between individuals and within the same individual. This has allowed us to quantify variation in elemental concentrations within individuals

(intra-individual variation), which would not have been possible had just one sample been provided. In addition, the variation between individuals (inter-individual variation) can be quantified via the random effects specification. One source of intra-individual variation that arises is the variation in the dilution of urine, which explains why applying a creatinine correction to account for dilution led to either a reduction or no significant difference in intra-individual variability in all of the elements for which mixed effects modelling was carried out. As an example, the intra-individual coefficient of variation for creatinine-corrected copper was around half that of uncorrected copper (45 vs 21%). Thus accounting for dilution via a creatinine correction has been shown to be effective in explaining some of the variation. The analytical methods used in this study were ‘tailored’ to the elements being measured and this allowed the quantification of some elements that would be difficult in a large multi-elemental analysis.

This study attempted to analyse the samples using routine methods that would be carried out in a single analysis or common group of elements. Beryllium and mercury are two elements that have specifically Venetoclax molecular weight benefited from single analysis for each element. In addition elements like platinum, tellurium and tantalum have benefited from being analysed in a hydrochloric acid matrix. This tailored approach has allowed 95th percentiles to be established for both beryllium and platinum and this has not always been the Methisazone case in other larger studies that have measured these elements (Hoet et al., 2013 and NHANES,

2011). However, a multi-elemental analysis undertaken by Heitland and Köster (2006) measuring 23 elements in one analysis reported both beryllium and platinum results that compare well with the values found in this study. Gold and silver are unstable analytes when spiked into solutions and this leads to poor recoveries and so without established QC materials more work is required with these methods and their stability in frozen samples, however, the results for both elements showed that 97–98% of the samples were below the LOQ. It is also evident from the number of elements for which there is no CRM and EQA schemes that there is a need to add/include further elements in these CRMs and EQA schemes. In-house prepared pool urine samples spiked with known concentrations of these elements, whilst the best available approach currently, do not satisfactorily address the quality control for such a wide number of elements. Total arsenic was measured in this study within Method 2 in collision cell mode.

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