Within- and between-person variability of urinary phthalate metabolites and bisphenol analogues over seven days: Considerations of biomonitoring study design

Urine was used as a part of a human biomonitoring study based on the excretion kinetics of less-persistent contaminants, such as phthalates and bisphenol A (BPA). Despite the advantages of being non-invasive and easy to collect, urine can show a large variability of concentrations of phthalate metabolites and BPA within a person depending on sampling time. Therefore, it is essential to assess the variability of urinary concentrations for comprehensive sampling design in the context of exposure and risk assessments. In this study, 18 phthalate metabolites and eight BPs were measured in all spot urine (n = 401) collected from 12 participants for seven consecutive days to evaluate within- and between-person variabilities. The intraclass correlation coefficients (ICCs) for all spot urines were poor for monomethyl phthalate (ICC: 0.002) and BPA (0.121) but were moderate for monoethyl phthalate (0.514) and monobenzyl phthalate (0.462). Based on the results of di (2-ethylhexyl) phthalate (DEHP) metabolites, the half-life and differences in metabolic capability seem to affect the ICCs. Urinary mono (2-ethylhexyl) phthalate (MEHP), a primary metabolite of DEHP, was suggested as a short-term exposure marker of DEHP in our study. Creatinine- and specific gravity-adjusted concentrations of phthalate metabolites and BPs resulted in increased ICCs, implying requirements for randomly collected spot urine. Most analytes in the first morning voids (FMVs) were correlated significantly with those in the daily composites, suggesting the feasibility of FMVs to estimate the daily exposure dose. This study facilitates a more comprehensive sampling design and data interpretation strategy for human biomonitoring studies.

Automated summary

Urine is commonly used in human biomonitoring studies to measure the excretion kinetics of less-persistent contaminants. However, urine samples can show significant variability in the concentrations of phthalate metabolites and bisphenol A depending on the sampling time. This study evaluated within- and between-person variabilities of phthalate metabolites and bisphenol A in spot urine samples collected over seven consecutive days. Results showed that some metabolites had poor intraclass correlation coefficients, indicating a high variability within individuals. Adjusting for creatinine and specific gravity increased the correlation coefficients, suggesting the need for randomly collected spot urine samples. Furthermore, first morning voids were found to be significantly correlated with daily composites, indicating their potential in estimating daily exposure doses. Overall, this study provides insights into the variability of urine concentrations and suggests improved sampling design for biomonitoring studies.