Untargeted metabolomics analysis of toxicant exposed rat urines for biomarker discovery

Abstract

Di-(2-propylheptyl) phthalate (DPHP) is a toxic plasticizer in polyvinyl chloride and it is used in commercial applications such as cables and shoes The aim of this study is to discover biomarkers for human DPHP exposure assessment using mass spectrometry based-metabolomic approach and orthogonal partial least squares discriminant analysis (OPLS-DA) In phase I (exposure biomarker candidate discovery) OPLS-DA was used to model the difference of two urine sample groups collected from rats orally administered with 2 different DPHP doses of 300 and 1200 mg/kg body weight (n=15 respectively) The urine samples were analyzed by solid phase extraction-ultra performance liquid chromatography-high resolution mass spectrometry (SPE-UPLC-HRMS) Identification of biomarker candidates for DPHP exposure was achieved by S-plot As a result 31 exposure biomarker candidates were identified In phase II (exposure biomarker validation) those 31 candidates were validated as exposure biomarkers by examining dose-response relationship revealed by rat urine samples collected from rats orally administered with 5 different DPHP doses 0 150 300 600 and 1200 mg/kg body weight (n=3 respectively) Out of 31 validated biomarkers 28 biomarkers have not been reported in the previous literature These novel DPHP exposure biomarkers can be further investigated for their applications in human exposure assessment

Date of Award	2018 Aug 30
Original language	English
Supervisor	Pao-Chi Liao (Supervisor)