Metabolites of organophosphate esters in urine from the United States: Concentrations, temporal variability, and exposure assessment

Environ Int. 2019 Jan;122:213-221. doi: 10.1016/j.envint.2018.11.007. Epub 2018 Nov 16.


Organophosphate esters (OPEs) are widely used as flame retardants and plasticizers in consumer products, which contributes to widespread exposure of humans. OPE diester metabolites in urine have been used as biomarkers of human exposure to these chemicals. Little is known, however, about occurrence and temporal variability in urinary concentrations of OPE metabolites in humans. In this study, 11 OPE metabolites were measured in 213 urine samples collected from 19 volunteers from Albany, New York, United States, at 3-day intervals for five weeks to investigate temporal variability in urinary concentrations. Diphenyl phosphate (DPHP) and bis(1,3-dichloro-2-propyl) phosphate (BDCIPP) were the major OPE metabolites, detected in all urine samples at specific gravity (SG)-adjusted concentrations (geometric mean, GM) of 1060 and 414 pg/mL and creatinine (Cr)-adjusted concentration (GM) of 404 and 156 ng/g, respectively. Inter-day variability in urinary OPE metabolite concentrations in 19 individuals was evaluated by intraclass correlation coefficients (ICCs). The inter-day variability in Cr-adjusted OPE metabolite concentrations (ICC: 0.31-0.67) was lower than those of SG-adjusted (ICC: 0.19-0.71) and unadjusted urinary concentrations (ICC: 0.24-0.74). BDCIPP (ICC: 0.68) and bis(2-chloroethyl) phosphate (BCEP) (ICC: 0.67) concentrations showed a moderate-to-high reliability over the sampling period, whereas the other nine OPE metabolites exhibited a moderate reliability (ICC: 0.31-0.55). Urine samples were further stratified by gender, age, ethnicity, and body mass index (BMI). The concentrations of BDCIPP and DPHP were significantly lower in males with normal BMI (BMI: 18.5-25 kg/m2) than in females and other BMI categories (p < 0.01). Relatively high ICCs, indicating low inter-day variability, were observed for males (ICC: 0.35-0.71) of 30-40 years of age (ICC: 0.34-0.87) with normal BMI (ICC: 0.28-0.64). The daily exposure doses to OPEs were estimated from urinary concentrations of corresponding OPE metabolites. The estimated doses of triphenyl phosphate (TPHP) and triethyl phosphate (TEP), based on median urinary concentrations of their metabolites, were 19.4 and 24.0 ng/kg bw/day, and the exposure dose to ∑OPEs was estimated at 65.3 ng/kg bw/day. Overall, our results indicate a high ICC for Cr-adjusted urinary concentrations of 11 OPE metabolites in urine.

Keywords: Exposure assessment; ICC; Organophosphate esters; Temporal variability; Urinary metabolites.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Environmental Exposure* / analysis
  • Environmental Exposure* / statistics & numerical data
  • Esters / urine*
  • Female
  • Humans
  • Male
  • New York / epidemiology
  • Organophosphates / urine*


  • Esters
  • Organophosphates