• Component Description
• Eligible Sample
• Description of Laboratory Methodology
• Laboratory Method Files
• Laboratory Quality Assurance and Monitoring
• Data Processing and Editing
• Analytic Notes
• References
• Codebook
  • SEQN - Respondent sequence number
  • WTSB2YR - Environmental B 2-year weights
  • URXCNP - Mono(carboxynonyl) phthalate (ng/mL)
  • URDCNPLC - Mono(carboxynonyl) phthalate Comt Code
  • URXCOP - Mono(carboxyoctyl) phthalate (ng/mL)
  • URDCOPLC - Mono(carboxyoctyl) phthalate Comt Code
  • URXECP - MECP phthalate (ng/mL)
  • URDECPLC - MECP phthalate Comment Code
  • URXECPT - ECPT phthalate (ng/mL)
  • URDEPCLC - ECPT phthalate Comment Code
  • URXHIBP - MHIBP phthalate (ng/mL)
  • URDHIBLC - MHIBP phthalate Comment Code
  • URXMBP - Mono-n-butyl phthalate (ng/mL)
  • URDMBPLC - Mono-n-butyl phthalate Comment Code
  • URXMC1 - Mono-(3-carboxypropyl) phthalate (ng/mL)
  • URDMC1LC - Mono-(3-carboxypropyl) phthalate Comt
  • URXMCOH - MCOCH phthalate (ng/mL)
  • URDMCOLC - MCOCH phthalate Comment Code
  • URXMEP - Mono-ethyl phthalate (ng/mL)
  • URDMEPLC - Mono-ethyl phthalate Comment Code
  • URXMHBP - Mono-3-hydroxy-n-butyl phthalate (ng/mL)
  • URDMHBLC - MHBP phthalate Comment Code
  • URXMHH - MEHP phthalate (ng/mL)
  • URDMHHLC - MEHP phthalate Comment Code
  • URXMHHT - MHHT phthalate (ng/mL)
  • URDMHTLC - MHHT phthalate Comment Code
  • URXMHNC - MHNCH (ng/mL)
  • URDMCHLC - MHNCH phthalate Comment Code
  • URXMHP - Mono-(2-ethyl)-hexyl phthalate (ng/mL)
  • URDMHPLC - Mono-(2-ethyl)-hexyl phthalate Comt Code
  • URXMIB - Mono-isobutyl phthalate (ng/mL)
  • URDMIBLC - Mono-isobutyl phthalate Comment Code
  • URXMNP - Mono-isononyl phthalate (ng/mL)
  • URDMNPLC - Mono-isononyl phthalate Comment Code
  • URXMOH - MEOH phthalate (ng/mL)
  • URDMOHLC - MEOH phthalate Comment Code
  • URXMONP - Mono-oxoisononyl phthalate (ng/mL)
  • URDMONLC - Monooxoisononyl phthalate Comment Code
  • URXMZP - Mono-benzyl phthalate (ng/mL)
  • URDMZPLC - Mono-benzyl phthalate Comment Code

National Health and Nutrition Examination Survey

2017-2018 Data Documentation, Codebook, and Frequencies

Phthalates and Plasticizers Metabolites - Urine (PHTHTE_J)

Data File: PHTHTE_J.xpt

First Published: August 2021

Last Revised: NA

Component Description

Phthalates are a group of chemicals used to make plastics more flexible and harder to break. They are often called plasticizers. Some phthalates are used as solvents (dissolving agents) for other materials. They are used in many products, such as vinyl flooring, adhesives, detergents, lubricating oils, automotive plastics, plastic clothes (raincoats), and personal-care products (soaps, shampoos, hair sprays, and nail polishes). Phthalates are used widely in polyvinyl chloride plastics, which are used to make products such as plastic packaging film and sheets, garden hoses, inflatable toys, blood-storage containers, and medical tubing. 1,2-cyclohexane dicarboxylic acid, diisononyl ester (DINCH) is used as a replacement of some high molecular weight phthalates. Once phthalates or DINCH enter a person's body, they are converted into breakdown products (metabolites) that pass out quickly in urine.

Di-2-ethylhexyl phthalate (DEHP) is a commonly used plasticizer. The use of DEHP in the U.S. market appears to be decreasing, at least in part because of legislative efforts, while the use of di-isononyl phthalate (DiNP), one of the replacements of DEHP, and other phthalate alternatives, may be rising (Calafat et al. 2011; Zota et al. 2014). Di-2-ethylhexyl terephthalate (DEHTP), a structural isomer of DEHP and one of such alternatives, has been used as a plasticizer for polymers contained in consumer products (Beeler 1976). To better understand exposure to phthalates alternatives, mono-2-ethyl-5-hydroxyhexyl terephthalate (MEHHTP), mono-2-ethyl-5-carboxypentyl terephthalate (MECPTP), two metabolites of DEHTP, and monooxoisononyl phthalate (MONP), an additional metabolite of DiNP were quantified.

Biomeasures of phthalates and phthalates alternatives in humans are necessary to evaluate potential human health effects from exposure to these chemicals.

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

The test principle utilizes high performance liquid chromatography-electrospray ionization-tandem mass spectrometry (HPLC-ESI-MS/MS) for the quantitative detection in urine of the following metabolites: monoethyl phthalate (MEP), monobutyl phthalate (MBP), mono-isobutyl phthalate (MiBP), mono(3-carboxypropyl) phthalate (MCPP), mono(2-ethylhexyl) phthalate (MEHP), monobenzyl phthalate (MBzP), monoisononyl phthalate (MNP), mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono(2-ethyl-5-carboxypentyl) phthalate (MECPP), monocarboxyoctyl phthalate (MCOP), monocarboxynonyl phthalate (MCNP), and cyclohexane-1,2-dicarboxylic acid-mono (hydroxy-isononyl) ester (MHNCH) (Silva et al., 2007). Urinary MEHHTP, MECPTP and MONP were measured by an online solid phase extraction coupled with isotope dilution-high performance liquid chromatography tandem mass spectrometry approach previously described (Silva et al. 2013). Urine samples are processed using enzymatic deconjugation of the glucuronidated metabolites followed by online solid phase extraction (SPE) coupled with reversed phase HPLC-ESI-MS/MS. Assay precision is improved by incorporating isotopically labeled internal standards of the phthalate metabolites and MHNCH. In addition, 4-methyl umbelliferyl glucuronide is used to monitor deconjugation efficiency. This selective method allows for rapid detection of metabolites of commonly used phthalates and DINCH in human urine with limits of detection in the low ng/mL range.

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

There were no changes to the lab method, lab equipment, or lab site for this component in the NHANES 2017-2018 cycle.

Laboratory Method Files

Phthalates and Plasticizers Metabolites Laboratory Procedure Manual (August 2021)

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 were stored under appropriate frozen (-30°C) conditions until they were 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 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 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 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 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

Urinary metals were measured in a full sample of participants ages 3-5 and 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 are included in this data file and should be used when analyzing these data.

The analytes included in this dataset were measured for all examined participants aged 3-5 years, and in a one-third subsample of participants 6 years and older. For participants aged 3-5, their WTSB2YR are equivalent to their MEC exam sample weights. These participants have completed at least one physical exam component in the MEC; therefore, they all have an exam sample weight larger than “0,” regardless of their lab test results. For participants 6 years and older, special sample weights were created for the subsample. These special weights accounted for the additional probability of selection into the subsample, as well as the additional nonresponse to these lab tests. Therefore, if participants 6 years and older were selected as part of the one-third 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 Demographic Data 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 SEQN.

Starting in the 2015-2016 NHANES cycle, 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 the analytes in the data set. Two variables are provided for each of these analytes. The variable named ending in “LC” (ex., URDCNPLC) 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., URDCNPLC=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., URXCNP) provides the analytic result for the analyte.

The lower limit of detection (LLOD, in ng/mL) for the phthalates and plasticizers metabolites:

References

• Beeler AD. 1976. New Terephthalate Plasticizers for PVC. Plastics Engineering 32: 40-41.
• Calafat AM, Wong LY, Silva MJ, Samandar E, Preau JL, Jia LT, et al. 2011. Selecting Adequate Exposure Biomarkers of Diisononyl and Diisodecyl Phthalates: Data from the 2005-2006 National Health and Nutrition Examination Survey. Environ Health Perspect 119: 50-55.
• Caudill, S.P., Schleicher, R.L., Pirkle, J.L. Multi-rule quality control for the age-related eye disease study. Statist. Med. (2008) 27(20):4094-40106.
• Silva MJ, Jia T, Samandar E, Preau JL, Calafat AM. 2013. Environmental exposure to the plasticizer 1,2-cyclohexane dicarboxylic acid, diisononyl ester (DINCH) in US adults (2000-2012). Environ Res 126: 159-163.
• Silva MJ, Samandar E, Preau JL Jr, Reidy JA, Needham LL,Calafat AM. Quantification of 22 phthalate metabolites in human urine. J Chromatogr B Analyt Technol Biomed Life Sci. 2007 Dec 1;860(1):106-12.
• Westgard JO, Barry PL, Hunt MR, Groth T. A multi-rule Shewhart chart for quality control in clinical chemistry. Clin Chem. 1981 Mar;27(3):493-501.
• Zota AR, Calafat AM, Woodruff TJ. 2014. Temporal Trends in Phthalate Exposures: Findings from the National Health and Nutrition Examination Survey, 2001-2010. Environ Health Perspect 122: 235-241.

Codebook and Frequencies