title: Within-person reproducibility of urinary bisphenol A and phthalate metabolites over a 1 to 3 year period among women in the Nurses' Health Studies: a prospective cohort study.
abstract: BACKGROUND
  Associations of bisphenol A and phthalates with chronic disease health outcomes are increasingly being investigated in epidemiologic studies. The majority of previous studies of within-person variability in urinary bisphenol A and phthalate metabolite concentrations have focused on reproducibility over short time periods. Long-term reproducibility data are needed to assess the potential usefulness of these biomarkers for prospective studies, particularly those examining risk of diseases with long latency periods. Low within-person reproducibility may attenuate relative risk estimates and reduce statistical power to detect associations with disease. Therefore, we assessed within-person reproducibility of bisphenol A, eight phthalate metabolites, and phthalic acid in spot urine samples over 1 to 3 years among women enrolled in two large cohort studies.
  
  
  METHODS
  Women in the Nurses' Health Study and Nurses' Health Study II provided two spot urine samples, 1 to 3 years apart (n = 80 women for analyses of bisphenol A; n = 40 women for analyses of phthalate metabolites; n = 34 women for analyses of phthalic acid). To measure within-person reproducibility, we calculated Spearman rank correlation coefficients and intraclass correlation coefficients for creatinine-adjusted concentrations of bisphenol A, phthalate metabolites, and phthalic acid.
  
  
  RESULTS
  Over 1 to 3 years, within-person variability of bisphenol A was high relative to total variability (intraclass correlation coefficient = 0.14) and rankings of bisphenol A levels between time-points were weakly correlated (Spearman correlation = 0.19). Seven of the eight phthalate metabolites and phthalic acid demonstrated moderate within-person stability over time (Spearman correlation or intraclass correlation coefficient = 0.39-0.55). Restricting analyses to first-morning urine samples did not alter results.
  
  
  CONCLUSIONS
  Single measurements of bisphenol A in spot urine samples were highly variable within women over 1 to 3 years, indicating that investigation of associations between a single urinary bisphenol A measurement and disease risk may be challenging in epidemiologic studies. The majority of urinary phthalate metabolites and phthalic acid appeared moderately reproducible within women over time, suggesting single measurements may be useful in epidemiologic studies, although observed relative risks can be substantially attenuated.
authors.affiliation: Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 181 Longwood Ave, Boston, MA 02115, USA. nhmkt@channing.harvard.edu.
authors.forename: Mary K
authors.initials: MK
authors.lastname: Townsend
authors.forename: Adrian A
authors.initials: AA
authors.lastname: Franke
authors.forename: Xingnan
authors.initials: X
authors.lastname: Li
authors.forename: Frank B
authors.initials: FB
authors.lastname: Hu
authors.forename: A Heather
authors.initials: AH
authors.lastname: Eliassen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001559:Benzhydryl Compounds / Q000652:urine*; D015415:Biomarkers / Q000652:urine; D015331:Cohort Studies; D004781:Environmental Exposure; D004784:Environmental Monitoring / Q000379:methods*; D004785:Environmental Pollutants / Q000652:urine*; D006306:Health Surveys; D006801:Humans; D008875:Middle Aged; D010636:Phenols / Q000652:urine*; D010795:Phthalic Acids / Q000652:urine*; D011446:Prospective Studies; D015203:Reproducibility of Results; D012621:Seasons; D014481:United States; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D015415:Biomarkers; D004785:Environmental Pollutants; D010636:Phenols; D010795:Phthalic Acids; C032279:phthalic acid; C006780:bisphenol A; D000098826:Bisphenol A Compounds
references.citation: Environ Res. 2009 Aug;109(6):734-7
references.pmid: 19463991
references.citation: Proc Natl Acad Sci U S A. 2004 Jan 20;101(3):775-80
references.pmid: 14715905
references.citation: Philos Trans R Soc Lond B Biol Sci. 2009 Jul 27;364(1526):2063-78
references.pmid: 19528056
references.citation: J Sep Sci. 2011 Jun;34(11):1268-74
references.pmid: 21506272
references.citation: Environ Res. 2009 Jul;109(5):641-6
references.pmid: 19272594
references.citation: PLoS One. 2010 Jan 13;5(1):e8673
references.pmid: 20084273
references.citation: J Expo Sci Environ Epidemiol. 2012 Jul;22(4):376-85
references.pmid: 22354176
references.citation: Int J Androl. 2006 Feb;29(1):155-65; discussion 181-5
references.pmid: 16466535
references.citation: J Environ Public Health. 2012;2012:481641
references.pmid: 22363351
references.citation: Environ Health Perspect. 2012 Sep;120(9):1307-13
references.pmid: 22796563
references.citation: Fertil Steril. 2013 Jul;100(1):162-9.e1-2
references.pmid: 23579005
references.citation: Environ Health Perspect. 2012 May;120(5):739-45
references.pmid: 22262702
references.citation: PLoS One. 2011;6(10):e26868
references.pmid: 22046388
references.citation: Environ Health Perspect. 2011 Jul;119(7):983-8
references.pmid: 21406337
references.citation: Environ Health Perspect. 2008 Feb;116(2):173-8
references.pmid: 18288314
references.citation: Environ Health Perspect. 2002 May;110(5):515-8
references.pmid: 12003755
references.citation: Toxicol Lett. 2008 Jul 10;179(3):155-62
references.pmid: 18579321
references.citation: J Expo Sci Environ Epidemiol. 2007 Sep;17(6):567-72
references.pmid: 17410114
references.citation: Cancer Causes Control. 2006 Sep;17(7):889-99
references.pmid: 16841256
references.citation: J Expo Sci Environ Epidemiol. 2012 Jul;22(4):398-408
references.pmid: 22588214
references.citation: Circulation. 2012 Mar 27;125(12):1482-90
references.pmid: 22354940
references.citation: Anal Chem. 2005 May 1;77(9):2985-91
references.pmid: 15859620
references.citation: Environ Health Perspect. 2010 Dec;118(12):1748-54
references.pmid: 20797930
references.citation: Environ Health Perspect. 2004 Apr;112(5):571-4
references.pmid: 15064163
references.citation: J Womens Health. 1997 Feb;6(1):49-62
references.pmid: 9065374
references.citation: Environ Health Perspect. 2011 Jan;119(1):131-7
references.pmid: 21205581
references.citation: Environ Health Perspect. 2012 Dec;120(12):1640-4
references.pmid: 23052487
references.citation: Environ Sci Technol. 2013 Jan 15;47(2):958-67
references.pmid: 23234290
references.citation: Environ Health Perspect. 2010 Jun;118(6):825-32
references.pmid: 20185384
references.citation: Occup Environ Med. 2005 Nov;62(11):806-18
references.pmid: 16234408
references.citation: Environ Health Perspect. 2004 Dec;112(17):1734-40
references.pmid: 15579421
references.citation: Cancer Epidemiol Biomarkers Prev. 2010 Apr;19(4):938-46
references.pmid: 20332276