Reproducibility of the Blood and Urine Exposome: A Systematic Literature Review and Meta-Analysis

Endogenous and exogenous metabolite concentrations may be susceptible to variation over time. This variability can lead to misclassification of exposure levels and in turn to biased results. To assess the reproducibility of metabolites, the intraclass correla-tion coefficient (ICC) is computed. A literature search in three databases from 2000 to May 2021 was conducted to identify studies reporting ICCs for blood and urine metabolites. This review includes 192 studies, of which 31 studies are included in the meta-analyses. The ICCs of 359 single metabolites are reported, and the ICCs of 10 metabolites were meta-analyzed. The repro-ducibility of the single metabolites ranges from poor to excellent and is highly compound-dependent. The reproducibility of bisphenol A (BPA), mono-ethyl phthalate (MEP), mono -n-butyl phthalate (MnBP), mono-2-ethylhexyl phthalate (MEHP), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono-benzyl phthalate (MBzP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), methyl-paraben, and propylparaben is poor to moderate (ICC median: 0.32; range: 0.15-0.49), and for 25-hydroxyvitamin D [25(OH)D], it is excellent (ICC: 0.95; 95% CI, 0.90-0.99). Pharmacokinetics, mainly the half-life of elimination and exposure patterns, can explain reproducibility. This review describes the reproducibility of the blood and urine exposome, provides a vast dataset of ICC estimates, and hence constitutes a valuable resource for future reproducibility and clinical epidemiologic studies.

Automated summary

Endogenous and exogenous metabolite concentrations can vary over time, leading to misclassification of exposure levels and biased results. The intraclass correlation coefficient (ICC) is used to assess the reproducibility of metabolites. This review includes 192 studies, with 31 studies included in the meta-analysis, reporting ICCs for 359 single metabolites and meta-analyzing ICCs for 10 metabolites. The reproducibility of single metabolites varies widely and is compound-dependent.