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. Measurement of metabolite levels in urine is important to understanding exposure to these compounds in the general population.
PPMA (N-Acetyl-S-(6-hydroxy-2,4-cyclohexadien-1-yl)-L-cysteine) is a metabolite of benzene. Benzene is a group 1 carcinogen according to the IARC and is commonly found in crude oil, gasoline, and tobacco smoke.
MMA (N-Acetyl-S-methyl-L-cysteine) is a biomarker of methylating agents. Methylating agents are associated with tumor formation in the lungs, nasal cavity, liver, trachea, and esophagus in animal models (Konstantinou et. al., 2018).
All examined participants age 3 to 5 years and a one-third subsample of examined participants age 6 years and older were eligible.
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.
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.
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 were received after all analyses were complete. The data were not edited.
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. Additionally, availability of specimens for surplus projects is lower than for other laboratory tests performed on NHANES participants. 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 furtherdetails 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. Specific sample weights for this subsample, WTSSAJ2Y, are included in this data file and should be used when analyzing these data. The sample weights created for this file used the examination sample weight, i.e., WTMEC2YR, as the base weight. The base weight was adjusted for additional nonresponse to these lab tests and re-poststratified to the population total using sex, age, and race/Hispanic origin. Participants who were part of the eligible population but who did not provide a urine specimen, or did not have sufficient volume of biospecimens, or who did not give consent for their specimens to be used for future research are included in the file, but they have a sample weight assigned “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).
The variable URXUCR (urine creatinine) will not be reported in this file. URXUCR can be found in the data file titled “Albumin & Creatinine – Urine”.
Detection Limits
The detection limits were constant for all of the analytes in the data set. Two variables are provided for each of these analytes. The variable name ending in “LC” (ex., SSPPMALC) 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. The other variable (ex., SSPPMA) provides the analytic result for that analyte. For analytes with analytic results below the lower limit of detection (ex., SSPPMALC=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]) and rounded to the precision of the LLOD.
The lower limit of detection (LLOD, in ng/mL) for SSPPMA and SSMMAC:
| Variable Name | Analyte Name | LLOD |
|---|---|---|
| SSPPMA | N-Acetyl-S-(6-hydroxy-2,4-cyclohexadien-1-yl)-L-cysteine (ng/mL) | 1.91 |
| SSMMAC | N-Acetyl-S-methyl-L-cysteine (ng/mL) | 5.11 |
| Code or Value | Value Description | Count | Cumulative | Skip to Item |
|---|---|---|---|---|
| 6597.317346 to 1670271.9768 | Range of Values | 2226 | 2226 | |
| 0 | Participants 3+ years with no surplus lab specimen | 753 | 2979 | |
| . | Missing | 0 | 2979 |
| Code or Value | Value Description | Count | Cumulative | Skip to Item |
|---|---|---|---|---|
| 1.35 to 195 | Range of Values | 2225 | 2225 | |
| . | Missing | 754 | 2979 |
| Code or Value | Value Description | Count | Cumulative | Skip to Item |
|---|---|---|---|---|
| 0 | At or above the detection limit | 335 | 335 | |
| 1 | Below lower detection limit | 1890 | 2225 | |
| . | Missing | 754 | 2979 |
| Code or Value | Value Description | Count | Cumulative | Skip to Item |
|---|---|---|---|---|
| 3.61 to 1050 | Range of Values | 2224 | 2224 | |
| . | Missing | 755 | 2979 |
| Code or Value | Value Description | Count | Cumulative | Skip to Item |
|---|---|---|---|---|
| 0 | At or above the detection limit | 1542 | 1542 | |
| 1 | Below lower detection limit | 682 | 2224 | |
| . | Missing | 755 | 2979 |