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Title: Reference range levels of polycyclic aromatic hydrocarbons in the US population by measurement of urinary monohydroxy metabolites

Abstract

We developed a gas chromatography isotope-dilution high-resolution mass spectrometry (GC/Id-HRMS) method for measuring 14 polycyclic aromatic hydrocarbon (PAH) metabolites representing seven parent PAHs in 3 mL of urine at low parts-per-trillion levels. PAH levels were determined in urine samples collected in 1999 and 2000 from approximately 2400 participants in the National Health and Nutrition Examination Survey, and, for the first time, reference range values were calculated for these metabolites in the US population. Using this GC/ID-HRMS method, we found detectable concentrations for monohydroxy metabolite isomers of fluorene, phenanthrene, fluoranthene, pyrene, and chrysene, benzo[c]phenanthrene, and benz[a]anthracene. Some monohydroxy metabolite isomers of benzo[c]phenanthrene, chrysene, and benz[a]anthracene exhibited low detection frequencies that did not allow for geometric mean calculations. Our study results enabled us to establish a reference range for the targeted PAHs in the general US population.

Authors:
 [1];  [2];  [2];  [2];  [2];  [2];  [2];  [2];  [2]
  1. Division of Environment Health Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA 30341 (United States). E-mail: jag2@cdc.gov
  2. Division of Environment Health Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA 30341 (United States)
Publication Date:
OSTI Identifier:
20775308
Resource Type:
Journal Article
Resource Relation:
Journal Name: Environmental Research; Journal Volume: 100; Journal Issue: 3; Other Information: DOI: 10.1016/j.envres.2005.06.004; PII: S0013-9351(05)00087-3; Copyright (c) 2005 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ANTHRACENE; BIOLOGICAL MARKERS; CHRYSENE; FLUORENE; GAS CHROMATOGRAPHY; ISOMERS; ISOTOPE DILUTION; MASS SPECTROSCOPY; METABOLITES; NUTRITION; PHENANTHRENE; POLYCYCLIC AROMATIC HYDROCARBONS; PYRENE; URINE

Citation Formats

Grainger, James, Huang, Wenlin, Patterson, Donald G., Turner, Wayman E., Pirkle, James, Caudill, Samuel P., Wang, Richard Y., Needham, Larry L., and Sampson, Eric J. Reference range levels of polycyclic aromatic hydrocarbons in the US population by measurement of urinary monohydroxy metabolites. United States: N. p., 2006. Web. doi:10.1016/j.envres.2005.06.004.
Grainger, James, Huang, Wenlin, Patterson, Donald G., Turner, Wayman E., Pirkle, James, Caudill, Samuel P., Wang, Richard Y., Needham, Larry L., & Sampson, Eric J. Reference range levels of polycyclic aromatic hydrocarbons in the US population by measurement of urinary monohydroxy metabolites. United States. doi:10.1016/j.envres.2005.06.004.
Grainger, James, Huang, Wenlin, Patterson, Donald G., Turner, Wayman E., Pirkle, James, Caudill, Samuel P., Wang, Richard Y., Needham, Larry L., and Sampson, Eric J. Wed . "Reference range levels of polycyclic aromatic hydrocarbons in the US population by measurement of urinary monohydroxy metabolites". United States. doi:10.1016/j.envres.2005.06.004.
@article{osti_20775308,
title = {Reference range levels of polycyclic aromatic hydrocarbons in the US population by measurement of urinary monohydroxy metabolites},
author = {Grainger, James and Huang, Wenlin and Patterson, Donald G. and Turner, Wayman E. and Pirkle, James and Caudill, Samuel P. and Wang, Richard Y. and Needham, Larry L. and Sampson, Eric J.},
abstractNote = {We developed a gas chromatography isotope-dilution high-resolution mass spectrometry (GC/Id-HRMS) method for measuring 14 polycyclic aromatic hydrocarbon (PAH) metabolites representing seven parent PAHs in 3 mL of urine at low parts-per-trillion levels. PAH levels were determined in urine samples collected in 1999 and 2000 from approximately 2400 participants in the National Health and Nutrition Examination Survey, and, for the first time, reference range values were calculated for these metabolites in the US population. Using this GC/ID-HRMS method, we found detectable concentrations for monohydroxy metabolite isomers of fluorene, phenanthrene, fluoranthene, pyrene, and chrysene, benzo[c]phenanthrene, and benz[a]anthracene. Some monohydroxy metabolite isomers of benzo[c]phenanthrene, chrysene, and benz[a]anthracene exhibited low detection frequencies that did not allow for geometric mean calculations. Our study results enabled us to establish a reference range for the targeted PAHs in the general US population.},
doi = {10.1016/j.envres.2005.06.004},
journal = {Environmental Research},
number = 3,
volume = 100,
place = {United States},
year = {Wed Mar 15 00:00:00 EST 2006},
month = {Wed Mar 15 00:00:00 EST 2006}
}
  • A synchronous fluorescent spectroscopy (SFS) method was developed to measure pyrene-type metabolites in the bile of brown bullhead (Ameiurus nebulosus) and to estimate the exposure of fish to PAHs in four Lake Erie tributaries collected in the spring and fall of 1990 and 1991. For comparison, fish biliary benzo[a]pyrene (B[a]P) metabolites were also measured by HPLC/fluorescent detection (HPLC/F). Both methods showed that concentrations of biliary PAH metabolites of fish collected in polluted rivers were significantly higher than those collected from reference rivers. Concentrations biliary metabolites of fish caught in the Black River were five to 20 times greater than thosemore » collected in Old Woman Creek by SFS and three to five times greater by HPLC/F. Fish from the Cuyahoga River had four to 24 times more biliary PAH metabolites than fish from Old Woman Creek, measured by SFS, and five to 10 times more, measured by HPLC/F. Brown bullhead from the Toussaint River had fewer PAH metabolites than fish from Old Woman Creek. Correlation analyses of the two sets of data obtained by SFS and HPLC/F showed significance by both Pearson's sample correlation and Spearman's rank correlation. This study indicates that pyrene-type metabolites determined by SFS can be used to estimate B[a]P-type metabolites in fish bile. SFS appears to be a highly sensitive method for detecting PAH metabolites and, because of its simplicity, a cost-efficient method for screening large numbers of samples for exposure to PAHs in fish.« less
  • Metabolism is a key health risk factor following exposures to pro-carcinogenic polycyclic aromatic hydrocarbons (PAHs) such as dibenzo[def,p]chrysene (DBC), an IARC classified 2A probable human carcinogen. Human exposure to PAHs occurs primarily from the diet in non-smokers. However, little data is available on the metabolism and pharmacokinetics in humans of high molecular weight PAHs (≥4 aromatic rings), including DBC. We previously determined the pharmacokinetics of DBC in human volunteers orally administered a micro-dose (29 ng; 5 nCi) of [14C]-DBC by accelerator mass spectrometry (AMS) analysis of total [14C] in plasma and urine. In the current study, we utilized a novelmore » “moving wire” interface between ultra-performance liquid chromatography (UPLC) and AMS to detect and quantify parent DBC and its major metabolites. The major [14C] product identified in plasma was unmetabolized [14C]-DBC itself, (Cmax= 18.5 ± 15.9 fg/mL, Tmax= 2.1 ± 1.0 h), whereas the major metabolite was identified as [14C]-(+/-)-DBC-11,12-diol (Cmax= 2.5 ± 1.3 fg/mL, Tmax= 1.8 h). Several minor species of [14C]-DBC metabolites were also detected for which no reference standards were available. Free and conjugated metabolites were detected in urine with [14C]-(+/-)-DBC-11,12,13,14-tetraol isomers identified as the major metabolites, 56.3% of which were conjugated (Cmax= 35.8 ± 23.0 pg/pool, Tmax= 6-12 h pool). [14C]-DBC-11,12-diol, of which 97.5% was conjugated, was also identified in urine (Cmax= 29.4 ± 11.6 pg/pool, Tmax= 6-12 h pool). Parent [14C]-DBC was not detected in urine. This is the first dataset to assess metabolite profiles and associated pharmacokinetics of a carcinogenic PAH in human volunteers at an environmentally relevant dose, providing the data necessary for translation of high dose animal models to humans for translation of environmental health risk assessment.« less
  • Carcinogenic polycyclic aromatic hydrocarbons (PAHs) require metabolic activation in order to exert their tumorigenic activity, typically to the diol epoxides as predicted by the bay-region concept. While a number of synthetic methods toward these diol epoxides are described in the literature, it was felt that a new, entirely different approach may be needed that achieves regio- and stereochemically controlled synthesis of these metabolites, particularly the bay-region analogues. The authors delineate a generally applicable, efficient synthesis of PAH diol epoxides and trans-dihydrodiols and its application to the first synthesis of the putative active metabolites, the bay-region diol epoxides of the carcinogenmore » 1,4-dimethylphenanthrene (1,4-DMPh).« less
  • Polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) are persistent environmental pollutants originating from incomplete combustion of organic materials and synthetic sources. PAHs, PCBs, and PBDEs have all been shown to have a significant effect on human health with correlations to cancer and other diseases. Therefore, measuring the presence of these xenobiotics in the environment and human body is imperative for assessing their health risks. To date, their analyses require both gas chromatography and liquid chromatography separations in conjunction with mass spectrometry measurements for detection of both the parent molecules and their hydroxylated metabolites, making theirmore » studies extremely time consuming. Here in this work, we characterized PAHs, PCBs, PBDEs and their hydroxylated metabolites using ion mobility spectrometry coupled with mass spectrometry (IMS-MS) and in combination with different ionization methods including electrospray ionization (ESI), atmospheric pressure chemical ionization (APCI) and atmospheric pressure photoionization (APPI). Finally, the collision cross section and m/z trend lines derived from the IMS-MS analyses displayed distinct trends for each molecule type. Additionally, the rapid isomeric and molecular separations possible with IMS-MS showed great promise for quickly distinguishing the parent and metabolized PAH, PCB, and PDBE molecules in complex environmental and biological samples.« less
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