TY - JOUR
T1 - Identification of urinary biomarkers of exposure to di-(2-propylheptyl) phthalate using high-resolution mass spectrometry and two data-screening approaches
AU - Shih, Chia Lung
AU - Liao, Pao Mei
AU - Hsu, Jen Yi
AU - Chung, Yi Ning
AU - Zgoda, Victor G.
AU - Liao, Pao Chi
N1 - Funding Information:
This work was supported by grants ( MOST105-2923-M-006-005-MY3 and MOST103-2113-M-006-003-MY3 ) from the Ministry of Science and Technology , Taiwan.
Publisher Copyright:
© 2017 Elsevier Ltd
PY - 2018/2
Y1 - 2018/2
N2 - Di-(2-propylheptyl) phthalate (DPHP) is a plasticizer used in polyvinyl chloride and vinyl chloride copolymer that has been suggested to be a toxicant in rats and may affect human health. Because the use of DPHP is increasing, the general German population is being exposed to DPHP. Toxicant metabolism is important for human toxicant exposure assessments. To date, the knowledge regarding DPHP metabolism has been limited, and only four metabolites have been identified in human urine. Ultra-performance liquid chromatography was coupled with Orbitrap high-resolution mass spectrometry (MS) and two data-screening approaches—the signal mining algorithm with isotope tracing (SMAIT) and the mass defect filter (MDF)—for DPHP metabolite candidate discovery. In total, 13 and 104 metabolite candidates were identified by the two approaches, respectively, in in vitro DPHP incubation samples. Of these candidates, 17 were validated as tentative exposure biomarkers using a rat model, 13 of which have not been reported in the literature. The two approaches generated rather different tentative DPHP exposure biomarkers, indicating that these approaches are complementary for discovering exposure biomarkers. Compared with the four previously reported DPHP metabolites, the three tentative novel biomarkers had higher peak intensity ratios, and two were confirmed as DPHP hydroxyl metabolites based on their MS/MS product ion profiles. These three tentative novel biomarkers should be further investigated for potential application in human exposure assessment.
AB - Di-(2-propylheptyl) phthalate (DPHP) is a plasticizer used in polyvinyl chloride and vinyl chloride copolymer that has been suggested to be a toxicant in rats and may affect human health. Because the use of DPHP is increasing, the general German population is being exposed to DPHP. Toxicant metabolism is important for human toxicant exposure assessments. To date, the knowledge regarding DPHP metabolism has been limited, and only four metabolites have been identified in human urine. Ultra-performance liquid chromatography was coupled with Orbitrap high-resolution mass spectrometry (MS) and two data-screening approaches—the signal mining algorithm with isotope tracing (SMAIT) and the mass defect filter (MDF)—for DPHP metabolite candidate discovery. In total, 13 and 104 metabolite candidates were identified by the two approaches, respectively, in in vitro DPHP incubation samples. Of these candidates, 17 were validated as tentative exposure biomarkers using a rat model, 13 of which have not been reported in the literature. The two approaches generated rather different tentative DPHP exposure biomarkers, indicating that these approaches are complementary for discovering exposure biomarkers. Compared with the four previously reported DPHP metabolites, the three tentative novel biomarkers had higher peak intensity ratios, and two were confirmed as DPHP hydroxyl metabolites based on their MS/MS product ion profiles. These three tentative novel biomarkers should be further investigated for potential application in human exposure assessment.
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U2 - 10.1016/j.chemosphere.2017.10.162
DO - 10.1016/j.chemosphere.2017.10.162
M3 - Article
C2 - 29131975
AN - SCOPUS:85033374947
SN - 0045-6535
VL - 193
SP - 170
EP - 177
JO - Chemosphere
JF - Chemosphere
ER -