Bisphenol A and phthalate metabolite urinary concentrations: Daily and across pregnancy variability

Abstract

Phthalates and bisphenol A (BPA) are high production volume and ubiquitous chemicals that are quickly metabolized in the body. Traditionally, studies have relied on single spot urine analyses to assess exposure; ignoring variability in concentrations throughout a day or over a longer period of time. We compared BPA and phthalate metabolite results from urine samples collected at five different time points. Participants (n=80) were asked to collect all voids in a 24 h period on a weekday and then again on a weekend before 20 weeks of pregnancy. During the second and third trimesters and in the postpartum period, single spot urines were collected. Variability over time in urinary concentrations was assessed using intraclass correlation coefficients (ICCs) and the sensitivity to correctly classify a single sample as high or low versus the geometric mean (GM) of all samples was calculated. We found low reproducibility and sensitivity of BPA and all phthalate metabolites throughout pregnancy and into the postpartum period but much higher reproducibility within a day. Time of day when the urine was collected was a significant predictor of specific gravity adjusted exposure levels. We concluded that, if the interest is in average exposures across pregnancy, maternal/fetal exposure estimation may be more accurate if multiple measurements, collected across the course of the entire pregnancy, rather than a single spot measure, are performed.

Temporal variability of urinary concentrations of phthalate metabolites, parabens and benzophenone-3 in a Belgian adult population

“…On the other side, MnBP, MBzP, MEHP, 5-oxo-MEHP and 5-OH-MEHP presented a higher intra-individual variability than the between-subject variability. According to Rosner et al (Rosner, 2011), whereas moderate ICC (Z0.40) could indicate a sufficient reproducibility of biomarker levels to perform epidemiological studies, low ICC affects the exposure classification and proportionally reduces the relative risk (Adibi et al, 2008;Fisher et al, 2015). We observed acceptable levels of reliability for parabens, MiBP, MEP and BP3 allowing the performance of some association studies between pathology and exposure, even for an exposure window of several months, e.g.…”

“…First of all, the majority of the available studies investigating the intra-individual variability of phthalate, paraben and BP3 biomarkers have been carried out in some US populations (Hauser et al, 2004;Smith et al, 2012;Teitelbaum et al, 2008;Braun et al, 2012;Peck et al, 2010;Townsend et al, 2013;Adibi et al, 2008;Hoppin et al, 2002;Marcus et al, 2010;Preau et al, 2010;Baird et al, 2010;Meeker et al, 2011;Meeker et al, 2012;Philippat et al, 2013;Ferguson et al, 2014;Watkins et al, 2014) and only very few were performed outside the USA, for instance in Puerto Rico (Meeker et al, 2013;Cantonwine et al, 2014), Canada (Fisher et al, 2015), Asia (Suzuki et al, 2009;Engel et al, 2014) or in the European Union Koch et al, 2014;Fromme et al, 2007). The level of exposure, the distribution and the correlations between pollutants have already been demonstrated to vary from one country to another, highlighting the dependence of local commercial applications or the legislations in force on the sources and pathways of exposure to these pollutants (Dewalque et al, 2014a;Suzuki et al, 2009;Shirai et al, 2013).…”

Evaluation of Population and Individual Variances of Urinary Phthalate Metabolites in terms of Epidemiological Studies

“…In contrast to persistent organic pollutants with a high bioaccumulation potential, xenobiotic compounds with a large range of exposure levels and short metabolization and excretion rates are especially problematic in this regard. In such cases, instead of trying to increase cohort size, increasing the number of samples per study participant may produce a larger benefit as already stated by Fisher et al since averaging individual concentration values will yield much more reliable estimates of a given person's general exposure and thereby increase the chance of discovering correlations with parameters likely to result from long-term effects such as medical outcomes [21].…”

“…Since urinary phthalate metabolites are among the exposure parameters to be quantified, the question arose to what extent values obtained from individual spot samples at the 36 th week of pregnancy constitutes a representative measure for exposure during the whole pregnancy. Several studies focused on the variability of phthalate and metabolites in human urine even for gestation periods [20][21][22][23][24][25][26]. However still less is known about the common approach to use a single spot urine analysis for correlation to health outcomes in the context of epidemiological studies.…”

The role of human biological monitoring in health risk assessment

“…Several studies have assessed the intra-and inter-individual variability in biomonitoring data collected on volunteers (Li et al, 2010;Preau et al, 2010;Ye et al, 2011;Fisher et al, 2015), general population studies Hays et al, 2015) and occupational health studies (Tardif et al, 2002;Berthet et al, 2009). There are a range of factors which produce variability in the concentration of a biomarker and a clear understanding of these factors is critical for the proper interpretation of HBM data in health-risk context.…”