Inter-Day Variability of Metabolites of DEHP and DnBP in Human Urine-Comparability of the Results of Longitudinal Studies with a Cross-Sectional Study.

Abstract

In the current paper, we compare the inter-day variability of the metabolite concentration of di(2-ethylhexyl) phthalate (DEHP) and di-n-butyl phthalate (DnBP) in 247 morning urine samples obtained from 19 probands of different age and sex with the metabolite concentration in morning urine obtained from 215 probands of the “Tübingen Survey” cross-sectional study. In the first longitudinal study the morning urine of seven volunteers was collected four times a year for seven consecutive days (course of the year study). In a second study the morning urine of 12 students of a boarding school was collected on five consecutive days (course of a week study). For participants of the two different longitudinal studies we obtained mean concentrations in first void morning urine for mono(2-ethyl-5-hydroxyhexyl) phthalate (5OH-MEHP) in the range from 21.3 to 110 µg/L, 10.5 to 35.6 µg/L for mono(2-ethyl-5-oxohexyl) phthalate (5oxo-MEHP), and 45.5 to 143 µg/L for mono(2-ethyl-5-carboxypentyl) phthalate (5cx-MEPP). The corresponding relative standard deviations (rel. Std.D in %) for these DEHP-metabolites vary between 45.2% and 262%. The 50th percentiles vary for 5OH-MEHP between 17.5 and 65.6 µg/L, for 5oxo-MEHP between 9.0 and 20.3 µg/L and for 5cx-MEPP between 42.5 and 82.0 µg/L. For participants of the “Tübingen Survey” cross-sectional study the means vary for 5OH-MEHP between 58.2 and 85.0 µg/L, between 33.6 and 38.7 µg/L for 5oxo-MEHP and between 110 and 158 µg/L for 5cx-MEPP with rel. standard deviations in a range between 86.5 to 175%. The corresponding 50th percentiles vary for 5OH-MEHP between 26.5 and 42.3 µg/L, for 5oxo-MEHP between 18.0 and 26.3 µg/L, and for 5cx-MEPP between 57.2 and 77.6 µg/L. In order to compare the data from the longitudinal studies with the data from the cross-sectional study, the frequency distribution of the results of both types of studies was compared first. In a second step, the results of a t-test (p-values) was used to check whether the results of the long-term studies differ statistically significantly from the results of the cross-sectional study (p < 0.05). The present data show that the frequency distributions of DEHP-metabolites are comparable. For most of the participants respectively subject groups t-test results prove that no statistical significant difference between results obtained from longitudinal studies compared to the results of the cross-sectional study are apparent. The available data on the exposure of individual subjects mirror the data obtained from cross-sectional studies of the general population and give hints to the risk of individual increased DEHP exposure. Results also highlight the importance of living conditions on the risk of increased DEHP exposure.