Exposure to Bisphenol A and Triclosan Among Pregnant Women
Exposure to Bisphenol A and Triclosan Among Pregnant Women
Given the potential health concerns of prenatal exposure to BPA and TCS on the developing infant and on the physiological and behavioral changes during pregnancy that can affect exposure to and disposition of chemicals in the body (Moya et al. 2014), it is critical to have biomonitoring data on a large, diverse population of pregnant women for the critical window of development. Furthermore, data on the free and conjugated compounds will contribute to understanding the toxicokinetics and potential health risks of the biologically active compounds.
Total BPA urinary concentrations (unadjusted for urine dilution) have been measured in several cohorts of pregnant women in the United States, with medians ranging from 1.0 to 2.0 μg/L (Braun et al. 2011; Harley et al. 2013; Hoepner et al. 2013; Mortensen et al. 2014; Wolff et al. 2008), somewhat higher than we observed in the MIREC cohort (0.89 μg/L). Urinary concentrations of BPA in U.S. women ≥ 20 years of age (NHANES 2009–2010) [Centers for Disease Control and Prevention (CDC) 2013] were higher at the 50th (1.8 vs. 0.9 μg/L) and 95th (9.6 vs. 6.2 μg/L) percentiles than in MIREC (2008–2011). A previous comparison of U.S. and Canadian urinary concentrations of BPA in the general population was not able to identify any methodological differences to explain the statistically significant lower levels in Canada (LaKind et al. 2012), which might suggest that there are population differences (e.g., consumer product formulations or avoidance of BPA-containing products) in Canada.
Only one study has reported urinary concentrations of free BPA in pregnant women (Vandentorren et al. 2011); however, contamination of the samples from exogenous sources during collection likely occurred. Free BPA has been measured in the urine of nonpregnant adult populations with widely varying detection rates of ≤ 10% (Fox et al. 2011; Völkel et al. 2008; Ye et al. 2005) to > 70% (Liao and Kannan 2012; Schöringhumer and Cichna-Markl 2007). The comparable figure in our study was 43%.
A few studies have measured the conjugated forms of BPA in adult populations (e.g., Kim et al. 2003; Liao and Kannan 2012; Ye et al. 2005). In a study of 163 subjects in France, Harthé et al. (2012) reported a GM urinary concentration of BPAG of 4.64 μg/L (corresponding to 2.62 μg/L BPA), which represented 79% of urinary total BPA. The GM concentration of BPAG in our study was considerably lower at 0.80 μg/L, with a ratio of BPAG to total BPA of 90%.
There are a number of possible explanations for differences between studies in levels or proportions of free and total BPA, including disparities in laboratory methods and their sensitivity, differences in the study populations, hydrolysis of the conjugates, and contamination of the samples. Although free BPA has been measured in several studies (reviewed by Vandenberg et al. 2010), other authors have argued that the detection of free BPA resulted from contamination of the sample or deconjugation of the BPAG during storage or sample preparation (Dekant and Völkel 2008; Teeguarden et al. 2011). Because derivatization with dansyl chloride was the first step of the analytical procedure for free BPA and TCS determination in the present study, contamination by the free forms of these ubiquitous phenols was prevented during the subsequent steps of sample preparation (Provencher et al. 2014). Furthermore, our in-house reference materials showed no decrease in conjugate concentrations after several months of storage at –20°C, and our field blanks and prescreening of collection materials did not provide any evidence of contamination with BPA. Therefore, we believe that we minimized, as much as possible, potential sources of external contamination that could artifactually inflate urinary concentrations of free BPA in our participants. It should be noted, however, that on average, only about 1% of the total BPA was present in the unconjugated form and that the median free BPA was at the method's LOD.
There are some inconsistencies among studies that have identified major predictors of urinary BPA concentrations in pregnant women. For example, whereas our study and one in Spain (Casas et al. 2013) found higher BPA concentrations in younger women, studies in Puerto Rico (Meeker et al. 2013) and the United States (Braun et al. 2011; Quirós-Alcalá et al. 2013; Robledo et al. 2013) reported no significant associations with maternal age. Smoking and low education (< 12 years) were significant predictors of higher BPA concentrations in MIREC and in studies in Cincinnati, Ohio (n = 388; Braun et al. 2011) and Spain (n = 479; Casas et al. 2013), but not in studies in California (n = 470; Quirós-Alcalá et al. 2013), New York City (n = 568; Hoepner et al. 2013), Puerto Rico (n = 105; Meeker et al. 2013), or Korea (n = 757; Lee et al. 2014).
Similar to BPA, the predominant TCS metabolite measured in MIREC was the glucuronide form; however, free TCS was detected in about 80% of the urine samples. The median ratio of free to total TCS (0.57%) is comparable to that reported following oral ingestion of TCS in 10 volunteers, where 0.9% of the TCS excreted was reportedly in the free form 24–48 hr after exposure (Sandborgh-Englund et al. 2006).
Several studies have measured total TCS in urine from pregnant women (see Supplemental Material, Table S7 http://ehp.niehs.nih.gov/wp-content/uploads/123/4/ehp.1408187.s001.508.pdf). Median urinary concentrations were considerably higher in studies conducted in Puerto Rico (Meeker et al. 2013) and France (Philippat et al. 2012) than in those conducted in California (Biomonitoring California 2013), New York City (Philippat et al. 2013; Wolff et al. 2008), Spain (Casas et al. 2011), or MIREC. Regional and population differences may be related to the use and/or availability of consumer products containing TCS. There was no significant difference between median urinary TCS concentrations in U.S. women in NHANES 2009–2010 (11.1 μg/L; CDC 2013) or Canadian women in the Canadian Health Measures Survey 2009–2011 (16 μg/L; Health Canada 2013) compared with those in MIREC (8.7 μg/L).
Data on major predictors of TCS exposure are limited. In MIREC, urinary TCS concentrations were significantly elevated in women with a university degree (compared with those with less education), > $100,000 compared with ≤ $100,000 household income, ≥ 25 compared with < 25 years of age, and never smokers compared with former or current smokers. In the U.S. general adult population, TCS concentrations were significantly higher in households with income of ≥ $20,000; they appeared to peak in the third decade of life and then decline slowly thereafter (Calafat et al. 2008b). In Puerto Rico, maternal urinary TCS was higher in older pregnant women (> 30 years) but was not associated with maternal education or income (Meeker et al. 2013).
A major concern in conducting biomonitoring studies is potential contamination of biospecimens via materials and processes (Longnecker et al. 2013; Salgueiro-González et al. 2012; Ye et al. 2013), resulting in higher measured concentrations than were actually present. Alternatively, concentrations may be artifactually reduced if, for example, free TCS adheres to the collection containers or other materials (Provencher et al. 2014). In MIREC, the ratio of free to total TCS varied from a minimum of < 1% to 82.5%, indicating that this was likely not a consistent problem. The use of field and laboratory blanks and prescreening of collection materials can assist with identifying potential sources of contamination; we used these QC methods in the present study and found contamination not to be a concern.
Consideration of the ability of a single spot urine sample to predict an individual's exposure over a period of time is especially important for short-lived chemicals such as BPA and TCS. Previous studies have indicated that although the intraclass correlation coefficient (ICC) for BPA is low (< 0.25) across pregnancy (Braun et al. 2011; Fisher et al. 2014; Meeker et al. 2013; Philippat et al. 2013), the ICC for TCS is higher (> 0.47) (Bertelsen et al. 2014; Meeker et al. 2013; Philippat et al. 2013); the results presented here should be interpreted with this potential limitation of spot urine samples in mind.
Discussion
Given the potential health concerns of prenatal exposure to BPA and TCS on the developing infant and on the physiological and behavioral changes during pregnancy that can affect exposure to and disposition of chemicals in the body (Moya et al. 2014), it is critical to have biomonitoring data on a large, diverse population of pregnant women for the critical window of development. Furthermore, data on the free and conjugated compounds will contribute to understanding the toxicokinetics and potential health risks of the biologically active compounds.
Total BPA urinary concentrations (unadjusted for urine dilution) have been measured in several cohorts of pregnant women in the United States, with medians ranging from 1.0 to 2.0 μg/L (Braun et al. 2011; Harley et al. 2013; Hoepner et al. 2013; Mortensen et al. 2014; Wolff et al. 2008), somewhat higher than we observed in the MIREC cohort (0.89 μg/L). Urinary concentrations of BPA in U.S. women ≥ 20 years of age (NHANES 2009–2010) [Centers for Disease Control and Prevention (CDC) 2013] were higher at the 50th (1.8 vs. 0.9 μg/L) and 95th (9.6 vs. 6.2 μg/L) percentiles than in MIREC (2008–2011). A previous comparison of U.S. and Canadian urinary concentrations of BPA in the general population was not able to identify any methodological differences to explain the statistically significant lower levels in Canada (LaKind et al. 2012), which might suggest that there are population differences (e.g., consumer product formulations or avoidance of BPA-containing products) in Canada.
Only one study has reported urinary concentrations of free BPA in pregnant women (Vandentorren et al. 2011); however, contamination of the samples from exogenous sources during collection likely occurred. Free BPA has been measured in the urine of nonpregnant adult populations with widely varying detection rates of ≤ 10% (Fox et al. 2011; Völkel et al. 2008; Ye et al. 2005) to > 70% (Liao and Kannan 2012; Schöringhumer and Cichna-Markl 2007). The comparable figure in our study was 43%.
A few studies have measured the conjugated forms of BPA in adult populations (e.g., Kim et al. 2003; Liao and Kannan 2012; Ye et al. 2005). In a study of 163 subjects in France, Harthé et al. (2012) reported a GM urinary concentration of BPAG of 4.64 μg/L (corresponding to 2.62 μg/L BPA), which represented 79% of urinary total BPA. The GM concentration of BPAG in our study was considerably lower at 0.80 μg/L, with a ratio of BPAG to total BPA of 90%.
There are a number of possible explanations for differences between studies in levels or proportions of free and total BPA, including disparities in laboratory methods and their sensitivity, differences in the study populations, hydrolysis of the conjugates, and contamination of the samples. Although free BPA has been measured in several studies (reviewed by Vandenberg et al. 2010), other authors have argued that the detection of free BPA resulted from contamination of the sample or deconjugation of the BPAG during storage or sample preparation (Dekant and Völkel 2008; Teeguarden et al. 2011). Because derivatization with dansyl chloride was the first step of the analytical procedure for free BPA and TCS determination in the present study, contamination by the free forms of these ubiquitous phenols was prevented during the subsequent steps of sample preparation (Provencher et al. 2014). Furthermore, our in-house reference materials showed no decrease in conjugate concentrations after several months of storage at –20°C, and our field blanks and prescreening of collection materials did not provide any evidence of contamination with BPA. Therefore, we believe that we minimized, as much as possible, potential sources of external contamination that could artifactually inflate urinary concentrations of free BPA in our participants. It should be noted, however, that on average, only about 1% of the total BPA was present in the unconjugated form and that the median free BPA was at the method's LOD.
There are some inconsistencies among studies that have identified major predictors of urinary BPA concentrations in pregnant women. For example, whereas our study and one in Spain (Casas et al. 2013) found higher BPA concentrations in younger women, studies in Puerto Rico (Meeker et al. 2013) and the United States (Braun et al. 2011; Quirós-Alcalá et al. 2013; Robledo et al. 2013) reported no significant associations with maternal age. Smoking and low education (< 12 years) were significant predictors of higher BPA concentrations in MIREC and in studies in Cincinnati, Ohio (n = 388; Braun et al. 2011) and Spain (n = 479; Casas et al. 2013), but not in studies in California (n = 470; Quirós-Alcalá et al. 2013), New York City (n = 568; Hoepner et al. 2013), Puerto Rico (n = 105; Meeker et al. 2013), or Korea (n = 757; Lee et al. 2014).
Similar to BPA, the predominant TCS metabolite measured in MIREC was the glucuronide form; however, free TCS was detected in about 80% of the urine samples. The median ratio of free to total TCS (0.57%) is comparable to that reported following oral ingestion of TCS in 10 volunteers, where 0.9% of the TCS excreted was reportedly in the free form 24–48 hr after exposure (Sandborgh-Englund et al. 2006).
Several studies have measured total TCS in urine from pregnant women (see Supplemental Material, Table S7 http://ehp.niehs.nih.gov/wp-content/uploads/123/4/ehp.1408187.s001.508.pdf). Median urinary concentrations were considerably higher in studies conducted in Puerto Rico (Meeker et al. 2013) and France (Philippat et al. 2012) than in those conducted in California (Biomonitoring California 2013), New York City (Philippat et al. 2013; Wolff et al. 2008), Spain (Casas et al. 2011), or MIREC. Regional and population differences may be related to the use and/or availability of consumer products containing TCS. There was no significant difference between median urinary TCS concentrations in U.S. women in NHANES 2009–2010 (11.1 μg/L; CDC 2013) or Canadian women in the Canadian Health Measures Survey 2009–2011 (16 μg/L; Health Canada 2013) compared with those in MIREC (8.7 μg/L).
Data on major predictors of TCS exposure are limited. In MIREC, urinary TCS concentrations were significantly elevated in women with a university degree (compared with those with less education), > $100,000 compared with ≤ $100,000 household income, ≥ 25 compared with < 25 years of age, and never smokers compared with former or current smokers. In the U.S. general adult population, TCS concentrations were significantly higher in households with income of ≥ $20,000; they appeared to peak in the third decade of life and then decline slowly thereafter (Calafat et al. 2008b). In Puerto Rico, maternal urinary TCS was higher in older pregnant women (> 30 years) but was not associated with maternal education or income (Meeker et al. 2013).
A major concern in conducting biomonitoring studies is potential contamination of biospecimens via materials and processes (Longnecker et al. 2013; Salgueiro-González et al. 2012; Ye et al. 2013), resulting in higher measured concentrations than were actually present. Alternatively, concentrations may be artifactually reduced if, for example, free TCS adheres to the collection containers or other materials (Provencher et al. 2014). In MIREC, the ratio of free to total TCS varied from a minimum of < 1% to 82.5%, indicating that this was likely not a consistent problem. The use of field and laboratory blanks and prescreening of collection materials can assist with identifying potential sources of contamination; we used these QC methods in the present study and found contamination not to be a concern.
Consideration of the ability of a single spot urine sample to predict an individual's exposure over a period of time is especially important for short-lived chemicals such as BPA and TCS. Previous studies have indicated that although the intraclass correlation coefficient (ICC) for BPA is low (< 0.25) across pregnancy (Braun et al. 2011; Fisher et al. 2014; Meeker et al. 2013; Philippat et al. 2013), the ICC for TCS is higher (> 0.47) (Bertelsen et al. 2014; Meeker et al. 2013; Philippat et al. 2013); the results presented here should be interpreted with this potential limitation of spot urine samples in mind.
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