Detection of phthalate exposure markers in hairs using UPLC-HRMS for long-term exposure assessment

Abstract

The most common way of biomonitoring phthalate exposure is by detecting the urinary phthalate metabolites Because phthalate metabolites are rapidly excreted out of the body via urine urine samples are considered to represent short-term exposure Compared to urine hairs potentially provide a longer determination windows for several months The aim of this study is to identify di-2(propylheptyl) phthalate (DPHP) exposure markers in urine and hairs and to investigate whether hairs can be used for long-term exposure assessments using a rat model Wistar rats were orally administrated with 5 different DPHP dosages for 7 days The urine samples were collected during (the 1st and 7th days) and after (the 14th and 28th days) exposure to DPHP and hair samples were collected after exposure to DPHP (the 28th days) The exposure marker candidates were identified by mass defect filter (MDF) signal mining algorithm with isotope tracing (SMAIT) and orthogonal partial least squares-discriminant analysis (OPLS-DA) and validated by examining dose-response relationships in urine and hair samples In the 1st 7th 14th and 28th day urine MDF/SMAIT identified 12 19 5 and 0 validated exposure markers respectively and OPLS-DA identified 45 63 7 and 0 validated exposure markers respectively In the 28th day hair MDF/SMAIT identified 6 validated markers and OPLS-DA identified 31 markers The 108 exposure markers identified by MDF/SMAIT or OPLS-DA in the different day urine or hairs were used to investigate the long-term exposure assessment A total of 65 86 28 and 0 markers showed dose-response in the 1st 7th 14th and 28th day urine samples respectively In the 28th day hair 37 markers were observed dose-response The results indicate that hairs can be used for long-term exposure assessments of DPHP and represent the past exposure after stopping administration Using the 7th day urine and 28th day hair as representative to compare exposure markers in urine and hairs we observed that 5 markers were identified simultaneously in urine and hairs by MDF/SMAIT but 14 and 1 markers showed dose-response only in urine or hairs respectively OPLS-DA identified the 22 overlapping markers between urine and hairs but there were 48 and 14 markers showed dose-response only in urine and hairs respectively Besides we observed mono-(2-propylheptyl) phthalate (MPHP) which is a minor urinary DPHP metabolite showed dose-response in hairs but not in urine The intensity ranking of the 4 previously reported DPHP metabolites in urine was different from that in hairs These results indicate that the chemical structures may result in the difference of rankings of exposure markers in urine and hairs When hairs were used for log-term exposure assessments the exposure markers should be identified in hairs The structures of 12 out of 36 exposure markers in the 28th day hair were confirmed as DPHP structure-related metabolites Among these 12 exposure markers the intensity of 6 markers were greater than 4 known DPHP metabolites The 6 exposure markers might be better than 4 known DPHP metabolites used for exposure assessment because of higher signal intensity and potential structure specificity

Date of Award	2017 Aug 22
Original language	English
Supervisor	Pao-Chi Liao (Supervisor)