title: Correcting for the influence of sampling conditions on biomarkers of exposure to phenols and phthalates: a 2-step standardization method based on regression residuals.
abstract: BACKGROUND
  Environmental epidemiology and biomonitoring studies typically rely on biological samples to assay the concentration of non-persistent exposure biomarkers. Between-participant variations in sampling conditions of these biological samples constitute a potential source of exposure misclassification. Few studies attempted to correct biomarker levels for this error. We aimed to assess the influence of sampling conditions on concentrations of urinary biomarkers of select phenols and phthalates, two widely-produced families of chemicals, and to standardize biomarker concentrations on sampling conditions.
  
  
  METHODS
  Urine samples were collected between 2002 and 2006 among 287 pregnant women from Eden and Pélagie cohorts, from which phthalates and phenols metabolites levels were assayed. We applied a 2-step standardization method based on regression residuals. First, the influence of sampling conditions (including sampling hour, duration of storage before freezing) and of creatinine levels on biomarker concentrations were characterized using adjusted linear regression models. In the second step, the model estimates were used to remove the variability in biomarker concentrations due to sampling conditions and to standardize concentrations as if all samples had been collected under the same conditions (e.g., same hour of urine collection).
  
  
  RESULTS
  Sampling hour was associated with concentrations of several exposure biomarkers. After standardization for sampling conditions, median concentrations differed by--38% for 2,5-dichlorophenol to +80 % for a metabolite of diisodecyl phthalate. However, at the individual level, standardized biomarker levels were strongly correlated (correlation coefficients above 0.80) with unstandardized measures.
  
  
  CONCLUSIONS
  Sampling conditions, such as sampling hour, should be systematically collected in biomarker-based studies, in particular when the biomarker half-life is short. The 2-step standardization method based on regression residuals that we proposed in order to limit the impact of heterogeneity in sampling conditions could be further tested in studies describing levels of biomarkers or their influence on health.
authors.affiliation: Team of Environmental Epidemiology Applied to Reproduction and Respiratory Health, Inserm, Institut Albert Bonniot (U823), Grenoble, France.
authors.forename: Marion
authors.initials: M
authors.lastname: Mortamais
authors.forename: Cécile
authors.initials: C
authors.lastname: Chevrier
authors.forename: Claire
authors.initials: C
authors.lastname: Philippat
authors.forename: Claire
authors.initials: C
authors.lastname: Petit
authors.forename: Antonia M
authors.initials: AM
authors.lastname: Calafat
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Ye
authors.forename: Manori J
authors.initials: MJ
authors.lastname: Silva
authors.forename: Christian
authors.initials: C
authors.lastname: Brambilla
authors.forename: Marinus J C
authors.initials: MJ
authors.lastname: Eijkemans
authors.forename: Marie-Aline
authors.initials: MA
authors.lastname: Charles
authors.forename: Sylvaine
authors.initials: S
authors.lastname: Cordier
authors.forename: Rémy
authors.initials: R
authors.lastname: Slama
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000652:urine; D052244:Endocrine Disruptors / Q000652:urine*; D004781:Environmental Exposure / Q000032:analysis; D004784:Environmental Monitoring; D005260:Female; D006801:Humans; D016014:Linear Models; D010636:Phenols / Q000652:urine*; D010795:Phthalic Acids / Q000652:urine*; D011247:Pregnancy / Q000652:urine*; D013997:Time Factors; D016482:Urinalysis / Q000379:methods; D055815:Young Adult
chemical_list: D015415:Biomarkers; D052244:Endocrine Disruptors; D010636:Phenols; D010795:Phthalic Acids