Table of Contents

Component Description

Urinary Perchlorate: Perchlorate has been used as an oxidant in solid fuel propellants for rockets and missiles since the 1950s. Lesser amounts of perchlorate are used in matches and fireworks. Perchlorate can also form naturally in the environment and can accumulate in nitrate-rich mineral deposits mined for use in fertilizers. Drinking water, milk, and certain plants with high water content (e.g., lettuce) can be the main sources of perchlorate intake for humans. Perchlorate has been used medically to treat hyperthyroidism. Its inhibitory effect on thyroid hormone production has led to concerns that exposure even to low levels of perchlorate in the environment might affect vulnerable groups, such as pregnant women with inadequate iodine intake and infants for whom thyroid hormone levels must be maintained adequately for normal brain development. Perchlorate taken into the body is rapidly eliminated in the urine, within a matter of hours. Measurement of urinary perchlorate is useful to assess recent human exposure.

Urinary Nitrate and Thiocyanate: Nitrate and thiocyanate are polyatomic anions that can disrupt thyroid function by competitively inhibiting iodide uptake, similar to the action of perchlorate. Nitrate, thiocyanate, and perchlorate can reversibly bind to the sodium-iodide symporter (NIS) protein resulting in reduced iodine absorption by the thyroid. Nitrate, thiocyanate and perchlorate interact additively to impair iodide uptake by the thyroid. Therefore, assessment of the impact of perchlorate exposure on thyroid function should include assessment of nitrate and thiocyanate exposure. By assessing exposure to each of the three physiologically relevant NIS-inhibitors, the relative impact of each chemical on thyroid function can be estimated and appropriate regulatory action taken if exposures are negatively impacting thyroid hormone levels. Impaired thyroid function can lead to hypothyroidism, proliferative thyroid lesions, and impaired neurodevelopment in infants.

Nitrate poisoning can also lead to methemeglobinemia, primarily in infants. The prevalence of nitrate exposure is likely due to nitrate intake from both food and drinking water, with foods (e.g. vegetables, milk, dairy products) thought to account for the majority of nitrate intake for typical American adults. Nitrate anion can also form endogenously. Public health prevention efforts have reduced the prevalence of methemoglobinemia in the United States. A reference range for urinary nitrate will provide useful information relevant to nitrate poisoning and subclinical methemoglobinemia in the US.

Thiocyanate is also a biomarker of cyanide exposure from tobacco smoke or diet. Thiocyanate primarily forms in the body as a metabolite of cyanide from tobacco smoke or cyanogenic foods such as cassava. Exposure to toxic levels of cyanide can result from numerous chemical reactions. Lower levels of thiocyanate can also be found in milk, dairy products and some vegetables. Therefore, a defined reference range for thiocyanate will provide useful benchmark data in case of a cyanide exposure event.

Eligible Sample

Examined participants aged 6 years and older from a one-third sample.

Description of Laboratory Methodology

Urinary Perchlorate, Nitrate, and Thiocyanate: This method is a quantitative procedure for the measurement of nitrate, perchlorate, and thiocyanate in human urine using ion chromatography coupled with electrospray tandem mass spectrometry. Chromatographic separation is achieved using an IonPac AS16 column with sodium hydroxide as the eluent. 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 NHANES 2011-2012 Lab Methods for Perchlorate, Nitrate, and Thiocyanate for detailed description of the laboratory method used.

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 for analysis.

Detailed specimen collection and processing instructions are discussed in the NHANES Laboratory Procedures Manual (LPM). Vials are stored under appropriate frozen (–20°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 Act mandates. Detailed QA/QC instructions are discussed in the NHANES LPM.

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 2011-2012 Laboratory Data Overview for general information on NHANES laboratory data.

Subsample Weights

Urinary Perchlorate, Nitrate, and Thiocyanate were measured in a one third subsample of persons 6 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.

Variance Estimation

The analysis of NHANES laboratory data must be conducted with the key survey design and basic demographic variables. The NHANES Demographic Data File contains demographic and 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.

Links to NHANES Data Files

This laboratory data file can be linked to the other NHANES data files using the unique survey participant identifier SEQN.

Detection Limits

The lower detection limits (LLOD) were 0.05 ng/mL for urinary perchlorate, 700 ng/mL for urinary nitrate, and 20 ng/mL for urinary thiocyanate.

Two variables are provided for each of these analytes. The variable named URD___LC indicates whether the result was below the limit of detection. There are two values: “0” and “1””. “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 named URX___ provides the analytic result for that analyte. For analytes with analytic results below the lower limit of detection (i.e., URD___LC=1), an imputed fill value was placed in the analyte results field. This value is the lower limit of detection divided by square root of 2 (LLOD/sqrt(2)).

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.

 

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 6 YEARS - 150 YEARS

WTSA2YR - Subsample A weights

Variable Name:
WTSA2YR
SAS Label:
Subsample A weights
English Text:
Subsample A weights
Target:
Both males and females 6 YEARS - 150 YEARS
Code or Value Value Description Count Cumulative Skip to Item
12199.652219 to 643202.3505 Range of Values 2551 2551
. Missing 43 2594

URXUP8 - Urinary perchlorate (ng/mL)

Variable Name:
URXUP8
SAS Label:
Urinary perchlorate (ng/mL)
English Text:
Urinary perchlorate (ng/mL)
Target:
Both males and females 6 YEARS - 150 YEARS
Code or Value Value Description Count Cumulative Skip to Item
0.0354 to 240 Range of Values 2467 2467
. Missing 127 2594

URDUP8LC - Urinary perchlorate comment code

Variable Name:
URDUP8LC
SAS Label:
Urinary perchlorate comment code
English Text:
Urinary Perchlorate comment code
Target:
Both males and females 6 YEARS - 150 YEARS
Code or Value Value Description Count Cumulative Skip to Item
0 At or above the detection limit 2466 2466
1 Below lower detection limit 1 2467
. Missing 127 2594

URXNO3 - Urinary nitrate (ng/mL)

Variable Name:
URXNO3
SAS Label:
Urinary nitrate (ng/mL)
English Text:
Urinary nitrate (ng/mL)
Target:
Both males and females 6 YEARS - 150 YEARS
Code or Value Value Description Count Cumulative Skip to Item
495 to 1050000 Range of Values 2467 2467
. Missing 127 2594

URDNO3LC - Urinary nitrate comment code

Variable Name:
URDNO3LC
SAS Label:
Urinary nitrate comment code
English Text:
Urinary nitrate comment code
Target:
Both males and females 6 YEARS - 150 YEARS
Code or Value Value Description Count Cumulative Skip to Item
0 At or above the detection limit 2460 2460
1 Below lower detection limit 7 2467
. Missing 127 2594

URXSCN - Urinary thiocyanate (ng/mL)

Variable Name:
URXSCN
SAS Label:
Urinary thiocyanate (ng/mL)
English Text:
Urinary thiocyanate (ng/mL)
Target:
Both males and females 6 YEARS - 150 YEARS
Code or Value Value Description Count Cumulative Skip to Item
14.1421 to 46600 Range of Values 2467 2467
. Missing 127 2594

URDSCNLC - Urinary thiocyanate comment code

Variable Name:
URDSCNLC
SAS Label:
Urinary thiocyanate comment code
English Text:
Urinary thiocyanate comment code
Target:
Both males and females 6 YEARS - 150 YEARS
Code or Value Value Description Count Cumulative Skip to Item
0 At or above the detection limit 2465 2465
1 Below lower detection limit 2 2467
. Missing 127 2594

URXUCR - Urinary creatinine (mg/dL)

Variable Name:
URXUCR
SAS Label:
Urinary creatinine (mg/dL)
English Text:
Urinary creatinine (mg/dL)
Target:
Both males and females 6 YEARS - 150 YEARS
Code or Value Value Description Count Cumulative Skip to Item
4 to 800 Range of Values 2525 2525
. Missing 69 2594