There were several studies that measured organophosphate esters (OPEs) in foods to assess the dietary intake of OPEs but none has measured OPE metabolites (mOPEs) in the same samples. In this study, we measured the concentrations of OPEs and mOPEs in 87 food samples and in five tap water samples collected in Queensland, Australia belonging to eight food groups. Tris(2-chloroisopropyl) phosphate (TCIPP) (detection frequency (DF), 77%) and tributyl phosphate (TBP) (DF, 71%), were the most frequently detected OPEs, while dibutyl phosphate (DBP) (DF, 84%) and diphenyl phosphate (DPhP) (DF, 86%) were the most frequently detected mOPEs. Vegetables had the highest concentrations of both ∑ 9 OPEs and ∑ 11 mOPEs, with the mean concentrations of 2.6 and 17 ng/g wet weight. Compared with dust ingestion and inhalation, dietary intake was the most important exposure pathway for tris(2-chloroethyl) phosphate (TCEP) (4.1 ng/kg bw/day), TCIPP (25 ng/kg bw/day), and TBP (6.7 ng/kg bw/day), accounting for >75% of total intake. Furthermore, we found that the intakes of some mOPEs, that is, bis(1,3-dichloroisopropyl) phosphate (BDCIPP) and DPhP from diet were typically higher than that of their parent OPEs. Such high levels of mOPE intakes could interfere with the utilization of mOPEs as biomarkers for assessing OPE exposure and warrant further investigation.
Alzheimer disease (AD) can be diagnosed by clinical and neuropsychologic tests and at autopsy, but there are no simple effective diagnostic methods for detecting biomarkers in patients at early stages of cognitive impairment. Early metabolic alterations that may facilitate AD diagnosis have not been thoroughly explored. We applied a nontargeted metabonomic approach using ultrahigh-performance liquid chromatography-quadrupole time-of-flight mass spectrometry to analyze serum and urine samples from 46 patients with AD and 36 healthy controls. Metabolite profiles were processed using multivariate analysis to identify potential metabolites, which were further confirmed using tandem mass spectrometry. Ultrahigh-performance liquid chromatography mass spectrometry methods were additionally used to quantify potentially important biomarkers. Independent samples were then selected to validate the identified biomarkers. There was a clear separation between healthy controls and AD patients; AD patient samples had disordered amino acid and phospholipid metabolism and dysregulated palmitic amide. Receiver operator characteristic curve and quantification suggested that palmitic amide, lysophosphatidylcholine (LysoPC, 18:0), LysoPC(18:2), L-glutamine, and 5-L-glutamylglycine were the optimal metabolites. In addition, areas under the curve from the palmitic amide, LysoPC(18:2), and 5-L-glutamylglycine in the validation study were 0.714, 0.996, and 0.734, respectively. These data elucidate the metabolic alterations associated with AD and suggest new biomarkers for AD diagnosis, thereby permitting early intervention designed to prevent disease progression.
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