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.
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When only serum is available, MEP and MiBP representing low molecular weight phthalates, and MECPP and MCiOP representing high molecular weight phthalates, have been used as indicators of phthalate exposure.
“However, when only serum was available for analysis, MEP and MiBP representing low molecular weight phthalates, and MECPP and MCiOP representing high molecular weight phthalates, have been used as indicators of phthalate exposure [77].”
From A Review of Biomonitoring of Phthalate Exposures (2019) · cites this paper as [77]
The “Serum and seminal plasma” section identifies MEP and MiBP as low-molecular-weight indicators and MECPP and MCiOP as high-molecular-weight indicators when only serum is available. It says they “could be used” for this purpose, however, rather than documenting that they have been used. (LLM, conf=0.84)
Experimental — accuracy not yet measuredMean concentrations of MEP, MBP, and DEHP metabolites were one to two orders of magnitude lower in serum and seminal plasma than in urine in young Danish men.
“The mean concentrations of MEP, MBP, and DEHP metabolites were one to two orders of magnitude lower in serum (MEP: 4.2, MBP: 0.4, and DEHP: 7.6 µg/L) and seminal plasma (1.0, 0.8, and 0.6 µg/L) than in urine (326, 42.5, and 115 µg/L).”
From A Review of Biomonitoring of Phthalate Exposures (2019) · cites this paper as [77]
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- Authors
- Frederiksen, H., Jorgensen, N., & Andersson, A.-M.
- Affiliations
- Copenhagen University Hospital (DK)
- Corresponding author
- Frederiksen, H.
- Venue
- Journal of Analytical Toxicology
- Publisher
- Oxford University Press (OUP)
- Published
- 2010-09-01
- Volume
- 34
- Issue
- 7
- Pages
- 400-410
- ISSN
- 0146-4760 (ISSN-L)
- 1945-2403
- OpenAlex
- W2150227280
- Cited by
- 204
- References
- 35
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 15 · 2023: 12 · 2022: 17 · 2021: 11 · 2020: 19 · 2019: 13 · 2018: 18 · 2017: 12 · 2016: 16 · 2015: 21 · 2014: 17 · 2013: 9 · 2012: 13
- FWCI
- 6.61
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Analytical Toxicology (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion)
- Funders
- Velux Fonden
- Topics
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Effects and risks of endocrine disrupting chemicals
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Pesticide Exposure and Toxicity
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Toxic Organic Pollutants Impact
- Keywords
- phthalate metabolites, DEHP metabolites, monoethyl phthalate, mono-n-butyl phthalate, monobenzyl phthalate, diisononyl phthalate, urinary biomarkers, serum biomarkers, seminal plasma, exposure assessment, endocrine disruptors
- MeSH terms
- Chromatography, Liquid, Denmark, Environmental Monitoring, Humans, Male, Phthalic Acids, Plasticizers, Semen, Biomarkers, Tandem Mass Spectrometry, Young Adult
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