Urinary trace element concentrations in environmental settings: is there a value for systematic creatinine adjustment or do we introduce a bias?

Systematic creatinine adjustment of urinary concentrations of biomarkers has been a challenge over the past years because the assumption of a constant creatinine excretion rate appears erroneous and the issue of overadjustment has recently emerged. This study aimed at determining whether systematic creatinine adjustment is to be recommended for urinary concentrations of trace elements (TEs) in environmental settings. Paired 24-h collection and random spot urine samples (spotU) were obtained from 39 volunteers not occupationally exposed to TEs. Four models to express TEs concentration in spotU were tested to predict the 24-h excretion rate of these TEs (TEμg/24h) considered as the gold standard reference: absolute concentration (TEμg/l); ratio to creatinine (TEμg/gcr); TEμg/gcr adjusted to creatinine (TEμg/gcr-adj); and concentration adjusted to specific gravity (TEμg/l-SG). As, Ba, Cd, Co, Cr, Cu, Hg, Li, Mo, Ni, Pb, Sn, Sb, Se, Te, V and Zn were analyzed by inductively coupled argon plasma mass spectrometry. There was no single pattern of relationship between urinary TEs concentrations in spotU and TEμg/24h. TEμg/l predicted TEμg/24h with an explained variance ranging from 0 to 60%. Creatinine adjustment improved the explained variance by an additional 5 to ~60% for many TEs, but with a risk of overadjustment for the most of them. This issue could be addressed by adjusting TE concentrations on the basis of the regression coefficient of the relationship between TEμg/gcr and creatinine concentration. SG adjustment was as suitable as creatinine adjustment to predict TEμg/24h with no SG-overadjustment (except V). Regarding Cd, Cr, Cu, Ni and Te, none of the models were found to reflect TEμg/24h. In the context of environmental exposure, systematic creatinine adjustment is not recommended for urinary concentrations of TEs. SG adjustment appears to be a more reliable alternative. For some TEs, however, neither methods appear suitable.