Table of Contents

Component Description

Formaldehyde (FA) is an environmental chemical occurring in tobacco smoke, building materials, and furniture, among other sources (Pala et. al., 2008). FA was classified as carcinogenic to humans by the International Agency for Research in Cancer (IARC, 2006 and Cogliano et. al., 2005). People exposed to high levels of FA are at increased risks of nasopharyngeal cancer and lymphohematopoietic cancer, specifically myeloid leukemia (Clinical Chemistry Branch, 2019). FA is also produced by most living organisms as part of regular metabolic activities.

FA is highly reactive towards biomolecules and can react with proteins to form so called “adducts” (Metz et. al., 2004). Adducts with hemoglobin have successfully been used as biomarkers of exposure for a range of environmental chemicals (Osterman-Golkar et. al., 1976).

Eligible Sample

Examined participants aged 18 years and older from a one-third subsample were eligible. Additionally, to oversample adult smokers, those participants aged 18 years and older, not in the regular one-third subsample, who smoked at least 100 cigarettes in their entire lifetime (SMQ020=1) and now smoke cigarettes every day (SMQ040=1), were also included in this special subsample.

Description of Laboratory Methodology

This procedure describes a method to measure N-terminal hemoglobin adducts of Formaldehyde in human erythrocytes. It consists of 5 parts:

  1. Preparation of the specimen for measurement;
  2. Total hemoglobin measurement in the sample solution used for hemoglobin adduct measurements;
  3. Enzymatic digestion of the sample solution;
  4. Analysis of digested samples by HPLC-MS/MS; and
  5. HPLC-MS/MS data processing and evaluation.

 

Because results are reported in nanomol adduct per gram of hemoglobin used in the measurement, the amount of hemoglobin used for this analysis needs to be determined. Therefore, this procedure includes a commercial method for measuring total hemoglobin in clinical samples (Eilers, 1967).

Refer to the Laboratory Method Files section for a detailed description of the laboratory methods used.

This is a new component in the 2013-2014 survey cycle.

Laboratory Method Files

Formaldehyde Lab Procedure Manual (March 2020)

Laboratory Quality Assurance and Monitoring

Washed-packed red blood cell specimens were 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 the National Center for Environmental Health for testing.

The NHANES quality assurance and quality control (QA/QC) protocols meet the 1988 Clinical Laboratory Improvement Act 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 quality control 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 contract laboratories. In the MEC, these methods include performing blind split samples collected on “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 the contract laboratories, which outlined the use of Westgard rules (Westgard et. al., 1981) 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 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 2013-2014 Laboratory Data Overview for general information on NHANES laboratory data.

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

Formaldehyde was measured in a special smoking subsample of persons 18 years and older. Special sample weights are required to analyze these data properly. Specific sample weights for this subsample are included in this data file and should be used when analyzing these data.

Demographic and Other Related Variables
The analysis of NHANES laboratory data must be conducted using the appropriate survey design and demographic variables. The NHANES 2013-2014 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.

The Fasting Questionnaire File includes auxiliary information, such as fasting status, length of fast, and the time of venipuncture.

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 all of the analytes in the data set. Two variables are provided for each of these analytes. The variable named ended “LC” (ex., LBDFORLC) 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 prefixed LBX (ex., LBXFOR) provides the analytic result for that analyte. For analytes with analytic results below the lower limit of detection (ex., LBDFORLC =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 lower limit of detection (LLOD, in nmol/g HB) for FA is:

Variable Name 

 Analyte Description

 LLOD

LBXFOR

Formaldehyde

0.67

References

Codebook and Frequencies

SEQN - Respondent sequence number

Variable Name:
SEQN
SAS Label:
Respondent sequence number
English Text:
Respondent sequence number.
Target:
Both males and females 18 YEARS - 150 YEARS

WTFSM - Smoking weights

Variable Name:
WTFSM
SAS Label:
Smoking weights
English Text:
Smoking weights
Target:
Both males and females 18 YEARS - 150 YEARS
Code or Value Value Description Count Cumulative Skip to Item
6426.907677 to 456840.9815 Range of Values 2546 2546
0 No Lab Result 59 2605
. Missing 0 2605

LBXFOR - Formaldehyde (nmol/g HB)

Variable Name:
LBXFOR
SAS Label:
Formaldehyde (nmol/g HB)
English Text:
Formaldehyde (nmol/g HB)
Target:
Both males and females 18 YEARS - 150 YEARS
Code or Value Value Description Count Cumulative Skip to Item
12.3 to 236 Range of Values 2049 2049
. Missing 556 2605

LBDFORLC - Formaldehyde comment code

Variable Name:
LBDFORLC
SAS Label:
Formaldehyde comment code
English Text:
Formaldehyde comment code
Target:
Both males and females 18 YEARS - 150 YEARS
Code or Value Value Description Count Cumulative Skip to Item
0 At or above the limit of detection 2049 2049
1 Below limit of detection 0 2049
. Missing 556 2605