Abstract
Nonylphenol (NP) has been widely used for more than 50 years in the synthesis of NP ethoxylates, which are important nonionic surfactants. NP is considered an endocrine disruptor based on in vitro and in vivo animal studies. However, the toxic effects of NP in humans are unknown. Information regarding the metabolic fate of 4-t-nonylphenol (4-tNP), a mixture of commercial NP branched isomers, in mammalian species is limited. This information is critical for the identification of adequate biomarkers of exposure to NP that could be used for exposure and risk assessment. We identified metabolites of one 4-tNP isomer, namely, 4-(3′,6′-dimethyl-3′-heptyl) phenol (P363-NP), using rat and human liver microsomes. The P363-NP metabolites were extracted by on-line solid-phase extraction and then separated and detected using high-performance liquid chromatography/tandem mass spectrometry. Using the genuine standard, we unambiguously identified 4-(3′,6′-dimethyl-3′-heptyl) catechol (P363-NC) as the main P363-NP metabolite when using human liver microsomes. Based on their chromatographic behavior and mass spectral fragmentation patterns, several other metabolites were tentatively identified, including a hydroxylated P363-NP with the alcohol functional group on the branched alkyl chain and its oxidative metabolite, a catechol with a hydroxylated alkyl side chain. Furthermore, the metabolite profile of P363-NP using rat and human enzymes was compared. Our findings suggest that P363-NC could be used as a biomarker to assess exposure to 4-tNP, although additional research to evaluate its suitability as a biomarker is warranted.
Footnotes
-
This research was supported in part by an appointment (A.M.B.) to the Research Participation Program at the Centers for Disease Control and Prevention, National Center for Environmental Health, Division of Laboratory Sciences, administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the U.S. Department of Energy and Centers for Disease Control and Prevention.
-
Disclaimer: The use of trade names is for identification only and does not constitute endorsement by the U.S. Department of Health and Human Services or the Centers for Disease Control and Prevention. The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the Centers for Disease Control and Prevention.
-
Article, publication date, and citation information can be found at http://dmd.aspetjournals.org.
-
doi:10.1124/dmd.107.015578.
-
ABBREVIATIONS: NP, nonylphenol(s); NPE, nonylphenol ethoxylates(s); 4-tNP, 4-tert nonylphenol; 4-nNP, 4-normal nonylphenol; P363-NP, 4-(3′,6′-dimethyl-3′-heptyl) phenol; SPE, solid-phase extraction; HPLC, high-performance liquid chromatography; MS/MS, tandem mass spectrometry; P363-NC, 4-(3′,6′-dimethyl-3′-heptyl) catechol; au, arbitrary unit(s); RT, retention time; EPI, enhanced product ion; MRM, multiplereaction monitoring; 4-tOP, 4-tert-octylphenol.
- Received March 2, 2007.
- Accepted April 23, 2007.
- The American Society for Pharmacology and Experimental Therapeutics
DMD articles become freely available 12 months after publication, and remain freely available for 5 years.Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page.
|