Volatile Organic Compounds (Human Blood):
Exposure to volatile organic compounds (VOCs) is ubiquitous. Chronic exposure to extremely high levels of some VOCs can lead to cancer and neurocognitive dysfunction (1,2).
Nearly 200 air toxics 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 levels in blood is essential to determine the need for regulatory mechanisms to reduce the levels of hazardous air pollutants to which the general population is exposed.
Volatile Organic Compounds (Home Tap Water):
In addition to assessing levels of VOCs in blood, VOC levels will be measured in home tap water specimens provided by NHANES participants. Specifically, trihalomethanes (THMs) and the fuel additive methyl tertiary-butyl ether (MTBE) are measured in thesesamples.
In 1999, the eligible sample was a one-fourth subsample of persons 20–59 years; in 2000, it was a one-third subsample of persons 20–59 years. There were no component-specific exclusions.
Description of Laboratory Methodology
Measurements of Trihalomethanes (THMs) and MTBE in Tap
The prevalence of water disinfection by-products in drinking water
supplies has raised concerns about possible health effects from chronic
exposure to these compounds. The objective is to support studies
exploring the relationship between exposure to THMs and health
This automated analytical method uses headspace solid-phase microextraction (SPME) coupled with capillary gas chromatography and mass spectrometry (3). This method quantitates trace levels of THMs (chloroform, bromodichloromethane, dibromochloromethane, and bromoform) and MTBE in tap water. Detection limits of less than 100 pg/mL for all analytes and linear ranges of three orders of magnitude are adequate for measuring the THMs in tap water samples tested from across the United States. THMs are stable for extended periods in tap water samples after quenching of residual chlorine and buffering to pH 6.5, thus enabling larger epidemiologic field studies with simplified sample collection protocols.
Measurements of THMs and MTBE in Whole Blood
The prevalence of water disinfection by-products (e.g. THMs) in tap water has raised concerns about possible health effects from chronic exposure to these compounds. Exposure to the fuel oxygenate MTBE has also raised concerns. People can be exposed to THMs and MTBE through a variety of sources, including use of household tap water that contains these chemicals. The objective of this study is to support studies exploring the relationship between health effects and exposure to THMs and MTBE. THMs and MTBE were quantified in human blood using capillary gas chromatography (GC) and high-resolution mass spectrometry (MS) with selected ion mass detection and isotope-dilution techniques (4). This method quantified trace levels of THMs (chloroform, bromodichloromethane, dibromochloromethane, and bromoform) and MTBE in human blood. Analyte responses were adequate for measuring background levels after extraction of these volatile organic compounds with either purge-and-trap extraction or headspace SPME. Detection limits ranged from 0.3–2.4 pg/mL, with linear ranges of three orders of magnitude. This method provided adequate sensitivity for measuring the THMs and MTBE in most blood samples tested from diverse U.S. reference population.
Measurements of other VOCs in Whole Blood
An additional 11 VOCs were measured in human blood using SPME in conjunction with gas chromatography and bench top quadrupole mass spectrometer (5). A combination of SPME and multiple single-ion monitoring minimizes the interferences and chemical noise associated with whole-blood samples. Detection limits are below 50 ppt (pg/mL) for a majority of the VOCs tested.
Data Processing and Editing
Automated data collection procedures for the survey were introduced in NHANES 1999–2000. In the MECs and analytical laboratories, data for the laboratory component are recorded directly onto a computerized data collection form. The system is centrally integrated, and it allows for ongoing monitoring of much of the data. Although the complete blood count and pregnancy analyses are performed in the MEC laboratory, most analyses are conducted elsewhere by approximately 21 laboratories across the United States.
Guidelines have been developed that provide standards for naming variables, filling missing values, and handling missing records. NCHS staff, assisted by contract staff, has developed data-editing specifications that check data sets for valid codes, ranges, and skip- pattern consistencies and examine the consistency of values between interrelated variables. Comments have been reviewed and recoded. NCHS staff verifies extremely high and low values whenever possible, and numerous consistency checks are performed. Nonetheless, users should examine the range and frequency of values before analyzing data.
The data editing specifications are as follows:
- Age and gender checks
- Total number of observations complete for each field
- No field overlap, truncated values, or weird results
- Direct data entry (DDE) errors
- Abnormal results confirmed by lab
- Test algorithm performed • Checked comment codes to resolve missing results and missing records
- All missing results and missing MEC-examined records are accounted
- Duplicate records were verified and deleted
Laboratory Quality Assurance and Monitoring
Mobile Examination Centers (MECs)
Laboratory team performance is monitored using several techniques.
NCHS and contract consultants use a structured quality assurance evaluation during unscheduled visits to evaluate both the quality of the laboratory work and the quality-control procedures. Each laboratory staff person is observed for equipment operation, specimen collection and preparation; testing procedures and constructive feedback are given to each staff. Formal retraining sessions are conducted annually to ensure that required skill levels were maintained.
The NHANES QA/QC protocols meet the 1988 Clinical Laboratory Improvement Act mandates. Detailed QA/QC instructions are discussed in the NHANES LPM.
NHANES uses several methods to monitor the quality of the analyses performed by the contract laboratories. In the MEC, these methods include performing second examinations on previously examined participants and blind split samples collected on "dry run" sessions. In addition, contract laboratories randomly perform repeat testing on 2.0% of all specimens.
NCHS developed and distributed a quality control protocol for all the contract laboratories which outlined the Westgaard rules used when running 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 and Westat quarterly. The reports are reviewed for trends or shifts in the data. The laboratories are required to explain any identified areas of concern. NCHS/Westat is currently reviewing these reports.
Measures of volatile organic compounds in blood and water were assessed in a subsample of participants aged 20–59. Use the special weights included in this data file when analyzing data. Please refer to the Analytic Guidelines for further details on the use of sample weights and other analytic issues.
The analysis of NHANES 1999-2000 laboratory data must be conducted with the key survey design and basic demographic variables. The recommended procedure for variance estimation requires use of stratum and PSU variables (SDMVSTRA and SDMVPSU, respectively), which are included in the demographic data file for each data release. The NHANES 1999-2000 Household Questionnaire and Demographic Data Files contain demographic data, health indicators, and other related information collected during household interviews. The phlebotomy file includes auxiliary information such as the conditions precluding venipuncture. The demographic, household questionnaire and phlebotomy files may be linked to the laboratory data file using the unique survey participant identifier SEQN.
The detection limit was variable for many of the analytes in the data set. In addition two variables are provided for each of these analytes. The variable named LBD___LC indicates whether the result was below the limit of detection. There are three values: "0", "1", and "2". "0" means that the result was at or above the limit of detection. "1" indicates that the result was below the limit of detection. "2" means the result was above the limit of detection.
The other variable named LBX___ provides the analytic result for that analyte. In cases, where the result was below the limit of detection, the value for that variable is the detection limit divided by the square root of two.