Correlations Between Phthalate Metabolites in Urine, Serum, and Seminal Plasma from Young Danish Men Determined by Isotope Dilution Liquid Chromatography Tandem Mass Spectrometry

Abstract

Phthalates are suspected of endocrine disrupting effects. We aimed to develop an analytical method for simultaneous determination of several phthalate metabolites in human urine, serum, and seminal plasma and to study correlations between levels of metabolites in these matrices. Thirteen metabolites were determined in samples from 60 young Danish men. Metabolites of common di-ester phthalates were detected in most urine samples. Summed di-(2-ethylhexyl) phthalate (DEHP) metabolites were excreted in urine in the highest amount (median = 91.1 ng/mL), followed by monoethyl phthalate (MEP), mono-iso-butyl phthalate (MiBP), mono-n-butyl phthalate (MnBP), mono-benzyl phthalate (MBzP), and finally summed di-isononyl phthalate (DiNP) metabolites. All these metabolite levels correlated significantly, indicating that when a participant was highly exposed to one phthalate he was also highly exposed to other phthalates. Several metabolites were also detectable in serum and in seminal plasma, although in much lower levels. Significant correlations between MEP and MiBP levels in serum and urine were observed, showing that serum levels could be used as biomarkers of human exposure. For DEHP and DiNP metabolites, correlations between urine and serum levels were only observed for mono(2-ethyl-5-carboxypentyl) phthalate (MECPP) and mono-(4-methyl-7-carboxyheptyl) phthalate (MCiOP), indicating that these secondary carboxylated metabolites were better serum markers than primary metabolites [mono(2-ethylhexyl) phthalate (MEHP) and mono-iso-nonyl phthalate (MiNP)]. In seminal plasma, only MEP levels correlated significantly to levels in urine and in serum.