Component Description
Exposure to volatile organic compounds (VOCs) is
ubiquitous. Chronic exposure to extremely high levels of some VOCs can lead to
cancer and neurocognitive dysfunction. Urinary metabolites of VOCs can be
detectable in urine for a longer period of time than the parent VOCs can be
detected in blood.
Nearly 200 air toxicants have been associated
with adverse health effects in occupational studies or laboratory studies, but
have not been monitored in general population groups. Information on levels of
exposure to these compounds, as measured by their metabolite levels in urine,
is essential to determine the need for regulatory mechanisms to reduce the
levels of hazardous air pollutants to which the general population is exposed.
Eligible Sample
All examined participants aged 3 to 5 years and a one-third subsample of examined participants aged 6 years and older were eligible.
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 electrospray tandem mass spectrometry
(UPLC-ESI/MSMS) as described by Alwis et al., (2012). Chromatographic
separation is achieved using an Acquity UPLC® HSS T3 (Part no. 186003540, 1.8
µm 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.
Refer to the Laboratory Method Files section for a detailed description
of the laboratory methods used.
There were some changes to this cycle. The following analytes were dropped from 2017-2018 URX1DC, URX2DC, URXDPM, URXIPM1, URXMB1, URXMB2, URXPMA, and URXTCV. The following analyte URXTTC was added after being excluded from 2015-2016 cycle.
Laboratory Method Files
Volatile Organic Compounds (VOCs) Metabolites
(September 2022)
Laboratory Quality Assurance and Monitoring
Urine specimens are processed, stored, and
shipped to the Division of Laboratory Sciences, National Center for
Environmental Health, Centers for Disease Control and Prevention, Atlanta GA
for analysis.
Detailed instructions on specimen collection and
processing are discussed in the NHANES Laboratory Procedures Manual (LPM). Vials are stored under
appropriate frozen (–30°C) conditions until they are shipped to National Center
for Environmental Health for testing.
The NHANES quality assurance and quality control
(QA/QC) protocols meet the 1988 Clinical Laboratory Improvement Amendments
mandates. Detailed QA/QC instructions are discussed in the NHANES LPM.
Mobile Examination Centers
(MECs)
Laboratory team performance is monitored using
several techniques. NCHS and contract consultants use a structured competency
assessment evaluation during visits to evaluate both the quality of the
laboratory work and the QC procedures. Each laboratory staff member is observed
for equipment operation, specimen collection and preparation; testing
procedures and constructive feedback are given to each staff member. Formal
retraining sessions are conducted annually to ensure that required skill levels
were maintained.
Analytical Laboratories
NHANES uses several methods to monitor the
quality of the analyses performed by the CDC and contract laboratories. In the
MEC, these methods include performing blind split samples collected during “dry
run” sessions. In addition, contract laboratories randomly perform repeat
testing on 2% of all specimens.
NCHS developed and distributed a QC protocol for
all CDC and contract laboratories, which outlined the use of Westgard rules
(Westgard, et al., 1981) when testing NHANES specimens. Progress reports
containing any problems encountered during shipping or receipt of specimens,
summary statistics for each control pool, QC graphs, instrument calibration,
reagents, and any special considerations are submitted to NCHS quarterly. The
reports are reviewed for trends or shifts in the data. The laboratories are required
to explain any identified areas of concern.
All QC procedures recommended by the manufacturers were followed.
Reported results for all assays meet the Division of Laboratory Sciences’ QA/QC
performance criteria for accuracy and precision, similar to the Westgard 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
Refer to the 2017-2018 Laboratory Data Overview for
general information on NHANES laboratory data.
There are over 800 laboratory tests performed
on NHANES participants. However, not all participants provided biospecimens or
enough volume for all the tests to be performed. The specimen availability can
also vary by age or other population characteristics. Analysts should
evaluate the extent of missing data in the dataset related to the outcome of
interest as well as any predictor variables used in the analyses to determine
whether additional re-weighting for item non-response is necessary.
Please refer to the NHANES Analytic
Guidelines and the on-line NHANES Tutorial for
further details on the use of sample weights and other analytic issues.
Subsample Weights
The analytes included in this dataset were measured in all examined participants aged 3-5 years, and in a one-third subsample of participants 6 years and older. Special sample weights are required to analyze these data properly. Variable (WTSA2YR) encoding of the specific sample weights for this subsample is included in this data file and should be used when analyzing these data. These special sample weights were created to account for the subsample selection probability, as well as the additional nonresponse to these lab tests. Therefore, if participants were eligible for the subsample, but did not provide a urine specimen, they would have the sample weight value assigned as “0” in their records.
Demographic and Other
Related Variables
The analysis of NHANES laboratory data must be
conducted using the appropriate survey design and demographic variables. The
NHANES 2017-2018 Demographics
File contains demographic data, health indicators, and other related
information collected during household interviews as well as the sample design
variables. The recommended procedure for variance estimation requires use of
stratum and PSU variables (SDMVSTRA and SDMVPSU, respectively) in the
demographic data file.
This laboratory data file can be linked to the
other NHANES data files using the unique survey participant identifier (i.e.,
SEQN).
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. All data are rounded to
three significant figures or three decimal places, whichever is less precise.
The lower limit of detection (LLOD, in ng/mL) for urinary VOC
metabolites:
| VARIABLE NAME |
ANALYTE NAME |
LLOD |
| URXAAM |
N-Acetyl-S-(2-carbamoylethyl)-L-cysteine (ng/mL) |
2.20 |
| URXAMC |
N-Acetyl-S-(N-methylcarbamoyl)-L-cysteine (ng/mL) |
6.26 |
| URXATC |
2-Aminothiazoline-4-carboxylic acid (ng/mL) |
29.5 |
| URXBMA |
N-Acetyl-S-(benzyl)-L-cysteine (ng/mL) |
0.500 |
| URXBPM |
N-Acetyl-S-(n-propyl)-L-cysteine (ng/mL) |
1.20 |
| URXCEM |
N-Acetyl-S-(2-carboxyethyl)-L-cysteine (ng/mL) |
6.96 |
| URXCYHA |
N-Acetyl-S-(1-cyano-2-hydroxyethyl)-L-cysteine (ng/mL) |
2.60 |
| URXCYM |
N-Acetyl-S-(2-cyanoethyl)-L-cysteine (ng/mL) |
0.500 |
| URXDHB |
N-Acetyl-S-(3,4-dihydroxybutyl)-L-cysteine (ng/mL) |
5.25 |
| URXGAM |
N-Acetyl-S-(2-carbamoyl-2-hydroxyethyl)-L-cysteine (ng/mL) |
9.40 |
| URXHEM |
N-Acetyl-S-(2-hydroxyethyl)-L-cysteine (ng/mL) |
0.791 |
| URXHPM |
N-Acetyl-S-(3-hydroxypropyl)-L-cysteine (ng/mL) |
13.0 |
| URXHP2 |
N-Acetyl-S-(2-hydroxypropyl)-L-cysteine (ng/mL) |
5.30 |
| URXIPM3 |
N-Acetyl-S-(4-hydroxy-2-methyl-2-butenyl)-L-cysteine (ng/mL) |
1.20 |
| URXMAD |
Mandelic acid (ng/mL) |
12.0 |
| URX2MH |
2-Methylhippuric acid (ng/mL) |
5.00 |
| URX34M |
3- and 4-Methylhippuric acid (ng/mL) |
8.00 |
| URXMB3 |
N-Acetyl-S-(4-hydroxy-2-butenyl)-L-cysteine (ng/mL) |
0.600 |
| URXPHE |
N-Acetyl-S-(1-phenyl-2-hydroxyethyl)-L-cysteine + N-Acetyl-S-(2-phenyl-2-hydroxyethyl)-L-cysteine (ng/mL) |
1.00 |
| URXPHG |
Phenylglyoxylic acid (ng/mL) |
12.0 |
| URXPMM |
N-Acetyl-S-(3-hydroxypropyl-1-methyl)-L-cysteine (ng/mL) |
1.70 |
| URXTTC |
2-Thioxothiazolidine-4-carboxylic acid |
11.2 |