Within-person variability in urinary bisphenol A concentrations: Measurements from specimens after long-term frozen storage

Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA.
Environmental Research (Impact Factor: 4.37). 05/2009; 109(6):734-7. DOI: 10.1016/j.envres.2009.04.004
Source: PubMed


Bisphenol A (BPA) is an estrogenic contaminant of food and water associated with adverse developmental effects in laboratory animals. BPA has recently been linked to morbidity in adult humans, but studies of developmental effects in humans are methodologically more difficult. The ability to measure BPA in urine samples after long-term storage could aid in such studies. Because the half-life of BPA is < 6h, a single measurement would be useful only if the environmental exposure is relatively constant over weeks or months. Our aims were to evaluate the stability of BPA in specimens after 22-24 years of storage and to measure within-person temporal variability in urinary BPA.
We measured total BPA concentration by mass spectrometry in first-morning urine samples from 60 premenopausal women. We selected from each woman's stored daily collections three urine samples approximately 2 and 4 weeks apart. Samples were selected from both the follicular and luteal phases of the menstrual cycle to assess cycle effects. Temporal variability was assessed with mixed model regression and correlations.
BPA levels had an inter-quartile range from 1.1 to 3.1 ng/mg creatinine, slightly higher than levels in specimens from NHANES collected 3-11 years later. The Spearman correlation was approximately 0.5 for samples 2 weeks apart and 0.3 for samples 4 weeks apart. Menstrual cycle phase did not influence levels. BPA tended to increase during the three-year collection period, but not significantly.
The similar distribution to NHANES samples and correlation of BPA levels taken at 2-week intervals provide indirect evidence that BPA is relatively stable during long-term freezer storage. The correlations indicate generally stable exposures over periods of weeks. These findings suggest that developmental effects of BPA exposure could be investigated with measurements from stored urine.

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Available from: Pablo A Nepomnaschy,
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    • "In 2003, more than 6 billion pounds of BPA were produced worldwide [5], and production is expected to exceed 5.4 million tons this year (for detailed international market analysis, see Bisphenol A (BPA): 2015 World Market Outlook and Forecast up to 2019 from The United States Environmental Protection Agency (EPA) estimates that over 1 million pounds of BPA leaches into the environment each year and over 90% of tested humans have detectable BPA in their systems with the highest levels found in infants and children [6] [7] [8] [9] [10] [11]. BPA is an estrogenic compound [12]. "
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    ABSTRACT: The estrogenic properties of bisphenol A (BPA), a ubiquitous synthetic monomer that can leach into the food and water supply, have prompted considerable research into exposure-associated health risks in humans. Endocrine-disrupting properties of BPA suggest it may impact developmental plasticity during early life, predisposing individuals to disease at doses below the oral reference dose (RfD) established by the Environmental Protection Agency in 1982. Herein, we review the current in vivo literature evaluating the carcinogenic properties of BPA. We conclude that there is substantial evidence from rodent studies indicating that early-life BPA exposures below the RfD lead to increased susceptibility to mammary and prostate cancer. Based on the definitions of "carcinogen" put forth by the International Agency for Research on Cancer and the National Toxicology Program, we propose that BPA may be reasonably anticipated to be a human carcinogen in the breast and prostate due to its tumor promoting properties.
    Reproductive Toxicology 10/2015; DOI:10.1016/j.reprotox.2015.09.006 · 3.23 Impact Factor
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    • "However, evidence demonstrates that single measurements may reflect chronic exposure if daily exposure is consistent. In fact, moderately high correlations were found for BPA measurements taken 2 weeks apart (Spearman correlation 0.5), as were levels of diethyl phthalate and benzylbutyl phthalate over several weeks, with intraclass correlation coefficients of 0.48 and 0.53, respectively (Nepomnaschy et al., 2009). No phthalates were observed to vary across the menstrual cycle (Baird et al., 2010). "
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    ABSTRACT: Bisphenol A, benzophenone-type UV filters, and phthalates are chemicals in high production and use including in a range of personal care products. Exposure of humans to these chemicals has been shown to affect endocrine function. Although short-lived, widespread exposure may lead to continual opportunity for these chemicals to elicit health effects in humans. The association of these chemicals with incident uterine leiomyoma, an estrogen sensitive disease, is not known. Urinary concentrations of bisphenol A (BPA), five benzophenone-type UV filters (2-hydroxy-4-methoxybenzophenone (2OH-4MeO-BP), 2,4-dihydroxybenzophenone (2,4OH-BP), 2,2׳-dihydroxybenzophenone (2,2׳OH-4MeO-BP), 2,2׳4,4׳-tetrahydroxybenzophenone (2,2׳4,4׳OH-BP), and 4-hydroxybenzophenone (4OH-BP), and 14 phthalate monoesters were quantified in 495 women who later underwent laparoscopy/laparotomy at 14 clinical sites for the diagnosis of fibroids. Significantly higher geometric mean creatinine-corrected concentrations of BPA, 2,4OH-BP, and 2OH-4MeO-BP were observed in women with than without fibroids [BPA: 2.09 µg/g vs. 1.46 µg/g p=0.004; 2,4OH-BP:11.10 µg/g vs. 6.71 µg/g p=0.01; 2OH-4MeO-BP: 11.31 µg/g vs. 6.10 µg/g p=0.01]. Mono-methyl phthalate levels were significantly lower in women with than without fibroids (1.78 µg/g vs. 2.40 µg/g). However, none of the exposures were associated with a significant odds ratio even when adjusting for relevant covariates. There was a lack of an association between select nonpersistent chemicals and the odds of a fibroid diagnosis.
    Environmental Research 02/2015; 137. DOI:10.1016/j.envres.2014.06.028 · 4.37 Impact Factor
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    • "A number of studies have investigated temporal variability of urinary measures of BPA. Most have focussed on adults from the general population (Arakawa et al., 2004) (Christensen et al., 2012a; Lassen et al., 2013; Mahalingaihah et al., 2008; Nepomnaschy et al., 2009; Teitelbaum et al., 2008; Ye et al., 2011) and report large within-and between-individual variation in urinary measures. Few studies have looked at variability during pregnancy (Braun et al., 2011a, 2012; Casas et al., 2013; Meeker et al., 2013), and none have investigated potential variability in children b 6 years. "
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    ABSTRACT: Used frequently in food contact materials, bisphenol A (BPA) has been studied extensively in recent years, and ubiquitous exposure in the general population has been demonstrated worldwide. Characterizing within- and between-individual variability of BPA concentrations is important for characterizing exposure in biomonitoring studies, and this has been investigated previously in adults, but not in children. The aim of this study was to characterize the short-term variability of BPA in spot urine samples in young children. Children aged ≥2-<4years (n=25) were recruited from an existing cohort in Queensland, Australia, and donated four spot urine samples each over a two day period. Samples were analysed for total BPA using isotope dilution online solid phase extraction-liquid chromatography-tandem mass spectrometry, and concentrations ranged from 0.53 to 74.5ng/ml, with geometric mean and standard deviation of 2.70ng/ml and 2.94ng/ml, respectively. Sex and time of sample collection were not significant predictors of BPA concentration. The between-individual variability was approximately equal to the within-individual variability (ICC=0.51), and this ICC is somewhat higher than previously reported literature values. This may be the result of physiological or behavioural differences between children and adults or of the relatively short exposure window assessed. Using a bootstrapping methodology, a single sample resulted in correct tertile classification approximately 70% of the time. This study suggests that single spot samples obtained from young children provide a reliable characterization of absolute and relative exposure over the short time window studied, but this may not hold true over longer timeframes.
    Environment international 04/2014; 68C:139-143. DOI:10.1016/j.envint.2014.03.027 · 5.56 Impact Factor
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