• Component Description
• Eligible Sample
• Description of Laboratory Methodology
• Laboratory Quality Assurance and Monitoring
• Data Processing and Editing
• Analytic Notes
• References
• Codebook
  • SEQN - Respondent sequence number
  • WTSVOC2Y - VOC Subsample 2 yr MEC weight
  • URXUCR - Creatinine, urine (mg/dL)
  • URX1DC - N-acel-S-(1,2-dichlorovinl)-L-cys(ng/mL)
  • URD1DCLC - N-acel-S-(1,2-dichlorovinl)-L-cys comt
  • URX2DC - N-acel-S-(2,2-Dichlorvinyl)-L-cys(ng/mL)
  • URD2DCLC - N-acel-S-(2,2-Dichlorvinyl)-L-cys comt
  • URX2MH - 2-methylhippuric acid (ng/mL)
  • URD2MHLC - 2-methylhippuric acid comment code
  • URX34M - 3-methipurc acd & 4-methipurc acd(ng/mL)
  • URD34MLC - 3-methipurc acd & 4-methipurc acid comt
  • URXAAM - N-ace-S-(2-carbamoylethyl)-L-cys(ng/mL)
  • URDAAMLC - N-ace-S-(2-carbamoylethyl)-L-cys comt
  • URXAMC - N-ace-S-(N-methlcarbamoyl)-L-cys(ng/mL)
  • URDAMCLC - N-ace-S-(N-methlcarbamoyl)-L-cys comt
  • URXATC - 2-amnothiazolne-4-carbxylic acid(ng/mL)
  • URDATCLC - 2-amnothiazolne-4-carbxylic acid comt
  • URXBMA - N-acetyl-S-(benzyl)-L-cysteine(ng/mL)
  • URDBMALC - N-acetyl-S-(benzyl)-L-cysteine comt
  • URXBPM - N-acetyl-S-(n-propyl)-L-cysteine(ng/mL)
  • URDBPMLC - N-acetyl-S-(n-propyl)-L-cysteine comt
  • URXCEM - N-acetyl-S-(2-Carbxyethyl)-L-cys(ng/mL)
  • URDCEMLC - N-acetyl-S-(2-Carbxyethyl)-L-cys comt
  • URXCYM - N-acetyl-S-(2-cyanoethyl)-L-cyst(ng/mL)
  • URDCYMLC - N-acetyl-S-(2-cyanoethyl)-L-cyst comt
  • URXDHB - N-ace-S-(3,4-Dihidxybutl)-L-cys(ng/mL)
  • URDDHBLC - N-ace-S-(3,4-Dihidxybutl)-L-cys comt
  • URXDPM - N-ace-S-(dimethylphenyl)-L-cys(ng/mL)
  • URDDPMLC - N-ace-S-(dimethylphenyl)-L-cys comt
  • URXGAM - N-ac-S-(2-carbmo-2-hydxel)-L-cys(ng/mL)
  • URDGAMLC - N-ac-S-(2-carbmo-2-hydxel)-L-cys comt
  • URXHEM - N-ace-S-(2-Hydroxyethyl)-L-cys(ng/mL)
  • URDHEMLC - N-ace-S-(2-Hydroxyethyl)-L-cys comt
  • URXHP2 - N-ace-S-(2-hydroxypropyl)-L-cys(ng/mL)
  • URDHP2LC - N-ace-S-(2-hydroxypropyl)-L-cys comt
  • URXHPM - N-ace-S-(3-Hydroxypropyl)-L-cys(ng/mL)
  • URDHPMLC - N-ace-S-(3-Hydroxypropyl)-L-cys comt
  • URXPMM - N-a-s-(3-hydrxprpl-1-metl)-L-cys(ng/mL)
  • URDPMMLC - N-a-s-(3-hydrxprpl-1-metl)-L-cys comt
  • URXMAD - Mandelic acid(ng/mL)
  • URDMADLC - Mandelic acid comment code
  • URXMB3 - N-a-s-(4-hydrxy-2butn-l-yl)-L-cys(ng/mL)
  • URDMB3LC - N-a-s-(4-hydrxy-2butn-l-yl)-L-cys comt
  • URXMB2 - N-ac-s-(2-hydrxy-3-butnyl)-L-cys(ng/mL)
  • URDMB2LC - N-ac-s-(2-Hydrxy-3-butnyl)-L-cys comt
  • URXMB1 - N-a-s-(1-hydrxMet)-2-prpn)-L-cys(ng/mL)
  • URDMB1LC - N-a-s-(1-hydrxMet)-2-prpn)-L-cys comt
  • URXPHE - N-ace-s-(phenl-2-hydxyetl)-L-cys(ng/mL)
  • URDPHELC - N-ace-s-(phenl-2-hydxyetl)-L-cys comt
  • URXPHG - Phenylglyoxylic acid(ng/mL)
  • URDPHGLC - Phenylglyoxylic acid comment code
  • URXPMA - N-acetyl-s-(phenyl)-L-cysteine(ng/mL)
  • URDPMALC - N-acetyl-s-(phenyl)-L-cysteine comt
  • URXTCV - N-acetyl-s-(trichlorovinyl)-L-cys(ng/mL)
  • URDTCVLC - N-acetyl-s-(trichlorovinyl)-L-cys comt
  • URXTTC - 2-thoxothazlidne-4-carbxylic acid(ng/mL)
  • URDTTCLC - 2-thoxothazlidne-4-carbxylic comt

National Health and Nutrition Examination Survey

2005-2006 Data Documentation, Codebook, and Frequencies

Volatile Organic Compound (VOC) Metabolites - Urine (Surplus) (SSUVOC_D)

Data File: SSUVOC_D.xpt

First Published: February 2014

Last Revised: April 2022

Component Description

The Family Smoking Prevention and Tobacco Control Act of 2009 gave the Food and Drug Administration regulatory authority over tobacco products. In Section 907(a), the Act states that the Secretary of Health and Human Services shall establish tobacco product standards. These product standards shall also include provisions for the testing of the tobacco products. In order to determine the effectiveness of these product standards, it is critical that surveillance systems be in place before the standards are enacted to determine whether they impact exposure of people who continue to use tobacco product. NHANES is an ideal source of human samples for assessing smokers in multiple locations around the country. NHANES will provide the most robust dataset possible for identifying changes in exposure of smokers that should result from enactment of tobacco product standards.

We anticipate that the results of this survey of tobacco exposure biomarkers will be used by FDA, other government agencies, and research institutions. The NHANES data will be used to determine the effectiveness of initial product standards and direct whether further changes to product standards need to be made.

Exposure to volatile organic compounds (VOCs) is ubiquitous. Chronic exposure to high levels of some VOCs can lead to cancer and neurocognitive dysfunction. Nearly 200 VOCs have been associated with adverse health effects in occupational studies or laboratory studies, but have not been monitored in general population groups. Metabolites of some VOCs can be detected in urine following exposure events. Therefore, information on exposure to these compounds, as measured by their metabolite concentrations in urine, is essential to understand the levels of hazardous VOCs to which the general population is exposed.

Eligible Sample

Urine collected from participants in NHANES 2005-2006 aged 12 years and older from a one-half subsample were eligible. Tests were conducted on residual urine samples.

Description of Laboratory Methodology

This method is a quantitative procedure for the measurement of VOC metabolites in human urine using ultra performance liquid chromatography coupled with electro spray tandem mass spectrometry (UPLC-ESI-MS/MS) (Alwis et al., 2012). Chromatographic separation is achieved using an Acquity UPLC® HSS T3 (Part no. 186003540, 1.8 mm x 2.1 mm x 150 mm, Waters, Inc.) column with 15 mM ammonium acetate and acetonitrile as the mobile phases. The eluent from the column is ionized using an electrospray interface to generate and transmit negative ions into the mass spectrometer. Comparison of relative response factors (ratio of native analyte to stable isotope labeled internal standard) with known standard concentrations yields individual analyte concentrations.

Laboratory Quality Assurance and Monitoring

The analytical measurements were conducted following strict quality control/quality assurance CLIA guidelines. Along with the study samples, each analytical run included high- and low-concentration quality control materials (QCs) and reagent blanks to assure the accuracy and reliability of the data. The concentrations of the high-concentration QCs and the low-concentration QCs, averaged to obtain one measurement of high-concentration QC and low-concentration QC for each run, were evaluated using standard statistical probability rules (Caudill et al. 2008).

Data Processing and Editing

The data were reviewed. Incomplete data or improbable values were sent to the performing laboratory for confirmation.

Analytic Notes

Bias Adjustments Applied to VOC Metabolites in Urine Assay in NHANES 2005–2006 cycle (Surplus)

Several systematic biases were discovered in measurements of certain urinary VOC metabolites in the 2005 – 2006 and 2011 – 2012 NHANES cycles. Upon further investigation, in April 2022, the following adjustments have been applied to the previously published data and included in the present dataset.

A. Adjustment to correct calibrator errors of the CDC lab prepared calibration materials

During the 2005–2006 and 2011–2012 NHANES cycles, calibrators used for tests on several VOC metabolites were prepared from a multi-analyte stock solution formulated from neat materials prepared by the testing lab at CDC. Beginning with the NHANES 2015–2016 cycle, calibrators and the multi-analyte stock solution were prepared externally. A systematic bias was observed between the cycles that used in-house calibration materials and the cycle using externally prepared calibration materials. The systematic nature of these biases permitted retrospective adjustment through a statistical approach based on linear regression modeling where adjusted measurements are predicted from unadjusted measurements using suitable data. The “statistical recalibrations” implemented here have the general form of a univariate linear regression equation (accounting for dilution factors routinely used during measurement):

where exp[·] and ln(·) are the natural exponential and natural logarithm functions, respectively. Natural log-transformation of both the un-adjusted and adjusted measurements moderated adverse influence on model fit from extreme measurements. The estimated regression slope and intercept are m and b, respectively, which are tabulated below for each analyte. The dilution factor was accounted for only once for each analyte that underwent more than one statistical recalibration (e.g., URXMB3). Statistical recalibration for the mass fraction of salt (URXHP2, URXGAM) only required a regression slope (i.e., ).

The explanatory power of the linear regressions was excellent (), and residuals exhibited distributions with good approximation to normality, as well as stable variance over the observed range of measurements. These favorable diagnostics demonstrate the efficacy of statistical recalibration for the retrospective amelioration of systematic bias.

Correction for Change in Internal Standard

Isotopically labeled internal standards were not commercially available for URXMB3 and URXHP2 during analysis of NHANES 2005–2006. Instead, the lab used surrogate internal standards.  Isotopically labeled internal standards later became available for purchase and were used in the NHANES 2011–2012 cycle. A systematic bias between these two cycles was noted and confirmed to be due to the internal standard change.

Analyte	m used in correction	b used in correction
URXMB3	1.08034	0.73526
URXHP2	0.99437	0.21216

 

Correction for Variation in Preparation of Neat Native Metabolites Standards

Validations of the externally prepared calibrators suggested that the calibrators previously prepared by the CDC testing lab were inaccurate due to special requirements for handling and preparing accurate solutions from neat materials, some of which are highly hygroscopic. Below is the list of analytes affected and the corresponding adjustment factors used in correction equation.

Analyte	m used in correction	b used in correction
URXAMC	0.99687	0.12843
URXCEM	1.01462	-0.13642
URXDHB	0.99654	0.04687
URXHEM	1.00947	0.30195
URXHPM	0.98949	-0.23802
URXMAD	1.00736	-0.18993
URXTTC	1.03057	-0.0746
URXMB3	0.97491	-0.43202
URX2DC	1.00155	-0.32374

 

Correction for Mass Fraction of Salt in Neat Compound Standard

During the 2005–2006 and 2011–2012 NHANES cycles, calibrators were prepared from a multi-analyte stock solutions formulated from neat materials in-house. Beginning with the NHANES 2015–2016 cycle, calibrators and the multi-analyte stock solutions were prepared externally. A systematic bias between the cycles that used in-house calibration materials and the cycle using externally prepared calibration materials was observed for analytes listed in the table below. Further validation confirmed that the large mass fraction of salt in the neat materials was not accounted for during formulation of in-house calibration materials. This discrepancy between the calculated concentration of the calibrators and the actual concentration led to a systematic bias in results for URXHP2 and URXGAM.

Analyte	m used in correction
URXHP2	0.5471199
URXGAM	0.57755045

 

Correction for Stereoisomerism in Urine Samples

URXMB3 occurs in human urine predominantly in the cis isomer, but quantitation in the NHANES 2005–2006 and NHANES 2011–2012 cycles used standards containing the trans isomer. This discrepancy led to a systematic bias in the URXMB3 results. Neat material that is purely cis isomer cannot be readily obtained, but a predictive regression equation can account for these quantitative differences.

Analyte	m used in correction	b used in correction
URXMB3	0.97741	-0.18775

 

B. Adjustment to correct calibrator errors of calibration materials prepared by an external vendor

Correction of N-Acetyl-S-(3-Hydroxypropyl-1-Methyl)-L-Cysteine (URXPMM)

In the 2005-2006 and 2011-2016 NHANES cycles, calibrators used to test N-Acetyl-S-(3-hydroxypropyl-1-methyl)-L-cysteine (URXPMM) were externally prepared, by a vendor, from a multi-analyte stock solution formulated from neat materials. In 2021, accuracy solutions from a new vendor indicated a systematic bias. Validations conducted by the CDC testing lab confirmed that the large mass fraction of salt in the neat materials was not accounted for during formulation of the externally prepared calibration materials from the previous vendor. This discrepancy between the calculated concentration of the calibrators and the actual concentration led to a systematic bias in results for URXPMM. An algebraic correction factor of 0.565 were applied to the original URXPMM values and released in the present file as below:

URXPMM = URXPMM_Original × 0.565

Detection Limits

The detection limits were constant for the analytes in the data set. Two variables are provided for each of these analytes. The variable named ending in “LC” (ex., URDAAMLC) indicates whether the result was below the limit of detection: the value “0” means that the result was at or above the limit of detection, “1” indicates that the result was below the limit of detection. For analytes with analytic results below the lower limit of detection (ex., URDAAMLC=1), an imputed fill value was placed in the analyte results field. This value is the lower limit of detection divided by the square root of 2 (LLOD/sqrt [2]). The other variable prefixed URX (ex., URXAAM) provides the analytic result for the analyte.

The lower limit of detection (LLOD, in µg/L) for urine VOC metabolites:

VARIABLE	SAS LABEL	LLOD
URXAAM	N-Acetyl-S-(2-carbamoylethyl)-L-cysteine	2.2
URXAMC	N-Acetyl-S-(N-methylcarbamoyl)-L-cysteine	6.26
URXATC	2-Aminothiazoline-4-carboxylic acid	15
URXBMA	N-Acetyl-S-(benzyl)-L-cysteine	0.5
URXBPM	N-Acetyl-S-(n-propyl)-L-cysteine	1.2
URXCEM	N-Acetyl-S-(2-carboxyethyl)-L-cysteine	6.96
URXCYM	N-Acetyl-S-(2-cyanoethyl)-L-cysteine	0.5
URX1DC	N-Acetyl-S-(1,2-dichlorovinyl)-L-cysteine	12.6
URX2DC	N-Acetyl-S-(2,2-dichlorovinyl)-L-cysteine	4.7
URXDHB	N-Acetyl-S-(3,4-dihydroxybutyl)-L-cysteine	5.25
URXDPM	N-Acetyl-S-(dimethylphenyl)-L-cysteine	0.5
URXGAM	N-Acetyl-S-(2-carbamoyl-2-hydroxyethyl)-L-cysteine	9.4
URXHEM	N-Acetyl-S-(2-hydroxyethyl)-L-cysteine	0.791
URXHPM	N-Acetyl-S-(3-hydroxypropyl)-L-cysteine	13
URXHP2	N-Acetyl-S-(2-hydroxypropyl)-L-cysteine	5.3
URXPMM	N-Acetyl-S-(3-hydroxypropyl-1-methyl)-L-cysteine	1.13
URXMAD	Mandelic acid	12
URX2MH	2-Methylhippuric acid	5
URX34M	3-and 4-Methylhippuric acid	8
URXMB1	N-Acetyl-S-(1-hydroxymethyl-2-propenyl)-L-cysteine	0.7
URXMB2	N-Acetyl-S-(2-hydroxy-3-butenyl)-L-cysteine	0.7
URXMB3	N-Acetyl-S-(4-hydroxy-2-butenyl)-L-cysteine	0.6
URXPHE	N-Acetyl-S-(phenyl-2-hydroxyethyl)-L-cysteine	0.7
URXPHG	Phenylglyoxylic acid	12
URXPMA	N-Acetyl-S-(phenyl)-L-cysteine	0.6
URXTCV	N-Acetyl-S-(trichlorovinyl)-L-cysteine	3
URXTTC	2-Thioxothiazolidine-4-carboxylic acid	11.2

 

References

• Alwis KU, Blount BC, Britt AS, Patel D, Ashley DL. 2012. Simultaneous analysis of 28 urinary VOC metabolites using ultra high performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry (UPLC-ESI/MSMS). Anal Chim Acta 750: 152– 160.
  
• Caudill SP, Schleicher RL, Pirkle JL. 2008. Multi-rule quality control for the age-related eye disease study. Stat Med 27:4094-4106.

Codebook and Frequencies