Concentration and distribution of parabens, triclosan, and triclocarban in pregnant woman serum in China

Journal Pre-proof Concentrations and distribution of parabens, triclosan, and triclocarban in pregnant woman serum in China

Aijing Li, Taifeng Zhuang, Qingqing Zhu, Maoyong Song, Chunyang Liao, Guibin Jiang PII:

S0048-9697(19)36386-7

DOI:

https://doi.org/10.1016/j.scitotenv.2019.136390

Reference:

STOTEN 136390

To appear in:

Science of the Total Environment

Received date:

23 October 2019

Revised date:

24 December 2019

Accepted date:

26 December 2019

Please cite this article as: A. Li, T. Zhuang, Q. Zhu, et al., Concentrations and distribution of parabens, triclosan, and triclocarban in pregnant woman serum in China, Science of the Total Environment (2019), https://doi.org/10.1016/j.scitotenv.2019.136390

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© 2019 Published by Elsevier.

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Concentrations and distribution of parabens, triclosan, and triclocarban in pregnant woman serum in China

Aijing Lia,c, Taifeng Zhuangb, Qingqing Zhua,c, Maoyong Songa,c,d, Chunyang Liaoa,c,d,*, Guibin Jianga,c

a

State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research

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Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing

Department of Pediatrics, Beijing Obstetrics and Gynecology Hospital, Capital

Medical University, Beijing 100026, China

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b

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100085, China

University of Chinese Academy of Sciences, Beijing 100049, China

d

Institute of Environment and Health, Jianghan University, Wuhan, Hubei 430056,

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c

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China.

*Corresponding author: Dr. Chunyang Liao Research Center for Eco-Environmental Sciences Chinese Academy of Sciences Beijing 100085, China Tel./Fax: 86-10-6291 6113 E-mail: [email protected]

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Abstract Despite mass production and widespread use of parabens, triclosan (TCS), and triclocarban (TCC) in a range of personal care products, little is known about their concentrations and distribution in pregnant woman serum in China. In this study, 5 parabens (methyl- (MeP), ethyl- (EtP), butyl- (BuP), heptyl- (HeP) and benzyl-parabens (BzP)) and 4 their metabolites (methyl protocatechuate (OH-MeP), ethyl protocatechuate (OH-EtP), 3,4-dihydroxybenzoic acid (3,4-DHB) and

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4-hydroxybenzoic acid (4-HB)), TCS, and TCC were measured, by using solid-phase extraction (SPE) and ultra-high performance liquid chromatography-tandem mass

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spectrometry (UPLC-MS/MS) techniques, in pregnant woman serum samples

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collected from 13 provinces in China. Total concentrations of parabens (∑PBs), their metabolites (∑MBs), and TCC and TCS (∑AAs) in serum ranged from 0.221-18.6

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(geometric mean (GM): 2.47), 47.4-598 (212), and 0.101-5.84 (1.01) ng/mL,

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respectively. MeP, EtP, 4-HB and TCS were the dominant compounds, and their GM concentrations were 1.86, 0.239, 211 and 1.00 ng/mL, respectively. Geographical

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distribution of target chemicals in serum was determined. Concentrations of MeP (5.49 ng/mL) and EtP (0.895 ng/mL) in sera from the Northeast China were higher

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than those from other regions (MeP: 0.987-3.54, EtP: 0.07-0.254 ng/mL; p < 0.05). The highest 4-HB concentrations were found in sera from the Southwest China (GM: 286 ng/mL), whereas the TCS concentrations in sera from the North China (1.18 ng/mL) were higher than those found for other regions (p < 0.05). The estimated daily intakes (EDIs; range: 49.5-126 μg/kg body weight (bw)/day) showed that the Chinese women were in a low health risk from exposure to such chemicals. This is the first study to report concentration profiles of parabens, TCS and TCC in pregnant woman serum in China.

Key words: Pregnant woman serum; Parabens and their metabolites; Triclosan; Triclocarban; Geographical distribution; Human exposure

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1. Introduction Parabens, triclosan (TCS) and triclocarban (TCC) are preservatives and antimicrobial agents added to a range of products including personal care products (PCPs), pharmaceuticals and foodstuffs (Castelain and Castelain, 2012; Wang et al., 2017). The use of these chemicals has resulted in their widespread occurrence in various environment matrices, such as river water (Ramaswamy et al., 2011), sewage sludge (Chen et al., 2019), sediment (Delgado et al., 2012), soil (Pérez et al., 2012),

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air and dust (Rudel et al., 2003). Occurrence of these chemicals in human has been reported, including urine (Shin et al., 2019), serum (Assens et al., 2019), and adipose

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tissue (Artacho-Cordón et al., 2018). Serum is a common matrix used to evaluate

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human exposure to diverse contaminants, since it possesses advantages of stability and precision (Ye et al., 2009). For example, Ye et al. (2009) investigated the stability

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of conjugates of several phenols, parabens and TCS in serum for 30 days at three

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temperatures (4 °C, room temperature, and 37 °C), and found that the percentage of conjugated species of parabens and TCS in serum specimens at 37 °C for 30 days did

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not vary significantly, and phenol conjugates seemed to be more stable in serum than urine. Moreover, serum sample can be used to evaluate the differences between

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regions and years in view of preciousness of the serum sample, and storage in hospital or specimen bank yearly. Therefore, we used serum as a matrix to explore the geographical distribution of target analytes and related exposure in pregnant women in this study.

Pathways of human exposure to parabens, TCS, and TCC mainly include ingestion of foodstuffs and pharmaceuticals (Dodge et al., 2015; Liao et al., 2013a), and dermal absorption of PCPs (Guo and Kannan, 2013). Previous studies showed that parabens were found in 40% - 60% of 170 PCPs and 20 baby care products from the United States (Guo and Kannan, 2013) and in 25% - 77% of 52 PCPs from China (Guo et al., 2014). A recent study reported that human exposure to parabens was much higher from foodstuffs and PCPs than pharmaceuticals (Ma et al., 2016). Parabens, TCS, and TCC are endocrine disrupting chemicals (EDCs), and their 3

Journal Pre-proof estrogenic and/or anti-estrogenic activities have been shown both in vitro and in vivo (Gomez et al., 2005; Henry and Fair, 2013; Pugazhendhi et al., 2005). Exposure to these EDCs has been linked to adverse health outcomes for pregnant women, such as oxidative stress and inflammation (Watkins et al., 2015), decrease in antral follicles count and quality of oocyte and embryo, and lower rate of clinical pregnancy and live births (Karwacka et al., 2019). Owing to their ubiquitous occurrence in the environment and potential adverse health effects to humans, international organizations or countries have proposed regulations or guidelines to limit the

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production and use of these chemicals. For example, in European Union (EU),

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parabens are allowed to use in PCPs at concentration of 0.4% (w/w) for single paraben and 0.8% for mixture of parabens (Błędzka et al., 2014). Food and Drug

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Administration (FDA) in United States implements similar regulations in the use of

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parabens as those of EU (Błędzka et al., 2014). Moreover, FDA prohibited the use of

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TCC and TCS in over-the-counter consumer antiseptic wash products in September 2016 (Halden et al., 2019). Consumption of PCPs in China is rapidly growing (Liu

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and Wong, 2013), which leads to environmental occurrence of and human exposure to parabens, TCS, and TCC (Chen et al., 2019; Zhu et al., 2019; Wang et al., 2015,

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2013).

In this study, 5 parabens (methyl- (MeP), ethyl- (EtP), butyl- (BuP), heptyl- (HeP) and benzyl-parabens (BzP)) and 4 their metabolites (methyl protocatechuate (OH-MeP), ethyl protocatechuate (OH-EtP), 3,4-dihydroxybenzoic acid (3,4-DHB) and 4-hydroxybenzoic acid (4-HB)), TCS, and TCC were measured in pregnant woman sera collected from several provinces, China. The baseline concentrations of these contaminants in serum were established and geographic patterns were assessed. On the basis of the measured concentrations in serum, human exposure doses to such contaminants were further examined.

2. Materials and methods 2.1 Reagents and standards 4

Journal Pre-proof Analytical standards of MeP, EtP, BuP, HeP, BzP, 4-HB and 3,4-DHB were purchased from AccuStandard Inc. (New Haven, CT, USA). OH-MeP, OH-EtP and TCC were purchased from TCI America (Portland, OR, USA), and TCS was from Alfa Aesar (Lancashire, United Kingdom). Deuterated standards of MeP-d4, HeP-d4, BzP-d4, 4-HB-d4, TCS-d3, and TCC-d4 were purchased from CDN Isotopes (Pointe-Claire, Quebec, Canada). HPLC grade acetonitrile and methanol were supplied by Thermo Fisher Scientific (Waltham, MA, USA). Analytical grade ammonium acetate (98%) and formic acid (96%) were purchased from Sinopharm

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Chemical Reagent Co. (Shanghai, China) and Sigma-Aldrich (St. Louis, MO, USA),

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respectively. Ultra-pure water was obtained from Milli-Q system (Millipore, Bedford, MA, USA). Molecular structures of target compounds are shown in Figure S1

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(Supporting Information).

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2.2. Sample collection

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A total of 162 pregnant woman (aged 19-41 years) serum samples were collected with help of the Obstetrics and Gynecology Hospital of the Capital Medical

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University, China, in 2016. Eligible participants were (1) older than 18 years; (2) resident of local city; (3) without pharmaceutical treatment, smoking and alcohol

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drinking during pregnancy; and (4) willing to provide blood samples. All Eligible participants have written the informed content. The research protocol was approved by ethics committees of the hospital. Blood samples were provided by mothers at the second trimester (T2: 19.3 ± 2.2 weeks). Serum samples were obtained by centrifuging the whole blood at 4500 rpm for 10min, and then stored at −80 °C until analysis. 2.3. Sample preparation Serum sample was thawed at room temperature and vortex-mixed, and 0.5 mL serum was transferred to a 15 mL polypropylene (PP) tube. After spiking 10 ng internal standards of MeP-d4, HeP-d4, BzP-d4, 4-HB-d4, TCS-d3, TCC-d4, 2 mL acetonitrile containing 2% formic acid was added. The sample was extracted by sonication (Kedao Ultrasonic Instrument Co., Shanghai, China) for 20min and then 5

Journal Pre-proof centrifuged at 4500 rpm for 10 min. The extraction process was repeated thrice. The combined supernatants were concentrated to 0.5 mL under the gentle stream of nitrogen and diluted to 10 mL with 0.2% formic acid aqueous solution. The sample was further purified by Oasis MCX SPE cartridge (60 mg/3 mL; Waters, Milford, MA, USA). The SPE cartridge was preconditioned with 5 mL methanol and 5 mL ultra-pure water, and then the samples were loaded and eluted with 5 mL methanol. The eluate was concentrated to 1 mL under nitrogen and filtered through 0.45 μm filter membrane before instrumental analysis.

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2.4. Instrumental analysis

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An Exion LC AD ultrahigh performance liquid chromatography coupled with 5500 triple quadrupole mass spectrometry (UPLC-MS/MS; AB Sciex, Framingham, MA,

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USA) was used for identification and quantification of target compounds. Target

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compounds were separated by a Symmetry C18 reversed phase column (2.1 mm×150

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mm, 3.5 µm; Waters). The mobile phase consisted of 2 mM ammonium acetate aqueous solution (A) and methanol (B) at a flow rate of 0.2 mL/min. The injection

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volume was 5 μL. The gradient elution program started from 25% B at 0 min, held for 1 min; increased to 60% B at 2.5min, held for 2 min; then increased to 99% B at 6.5

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min, held for 3 min; finally returned to 25% B at 9.5 min, held for 1.5 min. The ionization source temperature was 550 °C, and the ion spray voltage was set at −4500 V. The MS/MS was operated using multiple reaction monitoring (MRM) in negative ion mode. The optimized MRM transitions of target analytes are shown in Table S1. 2.5. Quality control and quality assurance Three method blank samples (0.5 mL ultra-pure water) and three matrix-spiked samples (0.5 mL pooled serum) were used to check possible contamination induced during the sample pretreatment and to monitor the recoveries of the analytical method. Only trace level of MeP (<0.05 ng/mL) was found in the method blank samples. Mean recoveries of target analytes (spiked with 10 ng standards) ranged from 75.1% (3,4-DHB) to 119% (4-HB). Target analytes were quantified by isotope-dilution method, and reported concentrations were corrected for by the recoveries of internal 6

Journal Pre-proof standards (MeP-d4 for MeP, EtP and BuP; HeP-d4 for HeP; BzP-d4 for BzP; 4-HB-d4 for 4-HB, 3,4-DHB, OH-MeP and OH-EtP; TCS-d3 for TCS; and TCC-d4 for TCC). The scope of the calibration curves ranged from 0.01-100 ng/mL and the coefficients of determination (r2) were ≥ 0.99. The limit of detection (LOD) and limit of quantitation (LOQ) were calculated by detecting spiked serum samples. LOD and LOQ were defined as the concentrations giving signal-to-noise ratios of 3 and 10, respectively. Details of the recoveries of analytes, LODs and LOQs are presented in Table S2. Two methanol samples and two quality control samples (with known

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concentrations) were detected in parallel with real samples. The methanol samples

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were used to check carry-over every 10 samples, and we did not find any measurable carry-overs. The quality control samples were used to evaluate the reproducibility of

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the analysis method, and results showed a coefficient variation of <10% for

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concentrations.

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2.6. Statistical analysis

Statistical analyses and graphics presentation were conducted using IBM SPSS

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Statistics 24 (International Business Machines Corp., Armonk, NY, USA) and OriginPro 8 software (OriginLab Corp., Northampton, MA, USA). The geometric

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mean (GM), median, minimum (Min), and maximum (Max) values were used to describe the data. Concentration below LOQ was replaced with LOQ divided by the square root of 2 for data analysis. Normality test was performed by plotting a Q-Q plot, and the data did not show normal distribution. Spearman’s test was used to examine the correlation between target compounds. Differences between age groups were tested by a non-parametric test with Mann-Whitney test. Results were considered significant if the two-tailed p-value was <0.05.

3. Results and discussion Participants came from 13 provinces (divided into 5 regions) in China. The mean age of all pregnant women was 31 years, ranging from 19-41 years. The detailed characteristics of pregnant women, including age and residency, are provided in Table 7

Journal Pre-proof S3. 3.1. Concentrations Concentrations of preservatives (parabens and their metabolites) and antibacterial agents (TCC and TCS) in pregnant woman serum samples are summarized in Table 1. On the whole, MeP, EtP, 4-HB, and TCS were the dominant compounds in serum, and their detection rates were in a range of 68.5% (EtP) -100% (4-HB). Concentrations of MeP and EtP ranged from 0.130-14.8 ng/mL (GM: 1.86 ng/mL) and 0.020-9.23 ng/mL (0.239 ng/mL), respectively. The GM 4-HB concentration (211 ng/mL) was

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2-3 orders of magnitude higher than those of MeP and EtP. OH-MeP was only found

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in a few samples (detection rate <5%). The TCS concentrations were in a range of 0.097-5.84 ng/mL (GM: 1.00 ng/mL). Global comparison of reported concentrations

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of parabens, TCS, and TCC in blood samples with those found in this study was

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performed. Our results indicated that the concentrations of MeP, EtP and TCS (median:

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3.08, 0.327, and 1.08 ng/mL) in serum from several Chinese provinces were lower than those found in maternal plasma from India (13.2, 1.01, and 6.19 ng/mL)

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(Shekhar et al., 2017), but higher than those found in pregnant woman blood from Denmark (0.850, not detected, and <0.220 ng/mL) (Assens et al., 2019) and Czech

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(MeP: 0.573 ng/mL) (Kolatorova et al., 2018). Relatively higher concentrations of MeP, EtP and TCS in maternal plasma from India may be caused by elevated levels of these chemicals in wastewater and river. In India, river water is still the most important drinking water resource, and household sewage and industrial effluents are discharged into river (Ramaswamy et al., 2011). The concentrations (median: 1.08 ng/mL) of TCS in pregnant woman serum were much higher than those of TCC (0.005 ng/mL), which is consistent with those found in serum from Beijing (TCS: 0.215, TCC: 0.048 ng/mL) (Wei et al., 2017) and Denmark (TCS (75th percentile concentration): 6.84 ng/mL, TCC: not detected) (Assens et al., 2019). The similar tendency was found in urine samples, and the urinary concentrations of TCS were considerably higher than those of TCC (Ashrap et al., 2018; Iyer et al., 2018). 3.2. Geographical distribution 8

Journal Pre-proof Serum samples were divided into five groups according to the residencies of pregnant women, including Northeast, North, East, Middle-south, and Southwest China. Concentrations of target analytes in different geographical regions are presented in Table S4 and Figure 1. MeP, EtP, 4-HB, and TCS were the predominant compounds in samples from every region. For parent parabens, the highest concentration of MeP was found in pregnant woman serum from the Northeast China (GM: 5.49 ng/mL), followed by, in a decrease order, the East (3.54 ng/mL), Middle-south (1.48 ng/mL), North (1.33 ng/mL), and Southwest China (0.987 ng/mL)

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(Table S4). The highest and lowest concentrations of EtP in serum were found in the

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Northeast (0.895 ng/mL) and Southwest China (0.070 ng/mL), respectively, suggesting consistency in the geographical distribution of serum parabens. Significant

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difference in paraben concentrations was observed in sera from different regions

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(p<0.05; Figure 1). Interestingly, the geographical distribution of serum parabens is

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consistent with that of sludge parabens from several administrative regions in China (Zhu et al., 2019). For metabolic parabens, the concentration of 4-HB in pregnant

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woman serum from the Northeast China (GM: 241 ng/mL) was significantly higher than that found for the North China (177 ng/mL; p<0.01), but lower than that found

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for the East China (271 ng/mL; p<0.05). For antibacterial agents, TCS was found in sera from all regions, with detection rate above 80%, while TCC was not detected in any samples (Table S4). The highest concentration of TCS was found in the North China (GM: 1.184 ng/mL), followed by the Northeast (1.036 ng/mL), Southwest (1.019 ng/mL), East (0.725 ng/mL), and Middlesouth China (0.714 ng/mL) (Table S4). 3.3. Correlations among target analytes Parabens in single or combination are widely used in food, pharmaceuticals and PCPs (Soni et al., 2005). Parabens are found in approximately 80% of PCPs (Błędzka et al., 2014), and considered the most common ingredient of PCPs, except for water (Cashman and Warshaw, 2005). Pregnant women are in a special period of pregnancy, and the use of PCPs and/or pharmaceuticals may cause adverse health effects to 9

Journal Pre-proof themselves and their fetuses. Therefore, it is important to investigate the sources of pollutants in pregnant women so that policy-makers can take corresponding measures to decrease the environment pollution and prevent human exposure. We analyzed correlations between concentrations of target chemicals in samples from individual regions (Figure 2) to explore whether these chemicals come from similar source or have similar environmental behavior. For serum samples from the Northeast China, a moderate positive correlation was observed between the MeP and 4-HB concentrations (r=0.591, p<0.01), indicating

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that serum 4-HB in pregnant women partly came from the metabolism of MeP.

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Previous studies have shown that 4-HB is a major metabolite of parabens (Aubert et al., 2012; Pugazhendhi et al., 2005). However, no significant correlations among the

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4-HB and other compounds concentrations were found. For serum samples from the

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North China, a strong correlation between the MeP and EtP concentrations was

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observed (r=0.869, p<0.01), indicating the existence of similar source for both chemicals. MeP and EtP can be added, as antimicrobial agents, to PCPs together

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(Haman et al., 2015). For serum samples from the East China, a weak correlation was observed between the MeP and EtP concentrations (r=0.354, p<0.01).

For the

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Middle-south China, a strong correlation between the MeP and EtP concentrations also was observed (r=0.807, p<0.01). Overall, we found that MeP and EtP had significant positive correlation (r= 0.775, p<0.01) in the entire sample set, and 4-HB was significantly positive correlated with MeP and EtP (r=0.316 and 0.216, respectively; p<0.01).

The relationship between the concentrations of four chemicals (MeP, EtP, 4-HB, TCS) and pregnant woman age was investigated (Figure S2). Maternal ages were classified into five age groups (under 25, 25-29, 30-34, 35-39 and above 39 years), according to a previous study (Waldenström and Ekéus, 2017). There were no significant difference in concentrations of MeP, EtP, and 4-HB among five age groups (Figure S2(a)). Significant difference in concentrations of TCS was observed among different age groups (p<0.05). The TCS concentration in serum from the 30-34 years 10

Journal Pre-proof group (GM: 1.11 ng/mL) was significantly higher than those from the <25 years (0.598 ng/mL) and 25-29 years groups (0.899 ng/mL; p<0.05, Figure S2(b)). TCS concentration in the >39 years group was significantly higher than that in the 25-29 years group (p<0.05). These results indicate that TCS body burden is higher in the older pregnant women. Consistent with our study, Arbuckle et al. (2015) and Huo et al. (2018) found higher urinary TCS concentration in women who were older. 3.4. Human exposure assessment Urine is usually used to evaluate human exposure to contaminants that can be

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excreted in the urine rapidly (Arbuckle et al., 2015; Vahedi et al., 2016). In this study,

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we transferred serum concentration to urinary concentration for target compounds to estimate daily intakes (EDI, μg/kg body weight (bw)/day) of parabens, TCS and TCC

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by using eq. 1 (Jin et al., 2018), based on the concentration ratio of contaminants

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between urine and serum (Rurine:serum) (Hines et al., 2015).

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EDI= 50×Rurine:serum× Cserum×V/BW (1)

Where Rurine:serum, the concentration ratio between urine and serum for parabens,

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was calculated according to a previously published study (Hines et al., 2015) and the 25th, 50th, 75th, and 95th percentiles of Rurine:serum were 24, 49, 177.5 and 376.4

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respectively. Cserum is the concentration of parabens in serum and the median and maximum concentrations were used for calculation. V is the urine excretion volume per day (L/day), which is assumed 1.2 L/day for women (Jin et al., 2018). The factor of 50 was used to account for the proportion of total parabens to parent parabens in urine (Ma et al., 2013). BW is the body weight (kg): 69 kg for pregnant women in China. Many studies used the average weight of Chinese women to calculate the EDI for chemical exposure (Jin et al., 2018; Ma et al., 2013), however, the body weight of pregnant women, especially in the second or third trimester, is higher than that of general adult women because of the fetal development. Therefore, we estimated the gestational weight gain (GWG) using eq. 2 (Robillard et al., 2018), and then added up the average weight of woman BW and GWG using eq. 3. opGWG = −1.2 ppBMI + 42 ± 2

(2) 11

Journal Pre-proof BWp= 54.4 + opGWG

(3)

Where opGWG (kg) is optimal gestational weight gain; ppBMI (kg/m2) is maternal pre-pregnancy body mass index, which was set as 22.8 kg/m2. It reported that the average body weight and height of Chinese females were 54.4 kg and 154.4 cm (Robillard et al., 2018), and BMI was calculated via dividing body weight (kg) by height (m2) (Jiang et al., 2015). Three target compounds (MeP, EtP and TCS) with detection rate above 50% were taken into account for calculation of EDIs. The calculated EDI values for MeP, EtP and TCS are shown in Table 2 (based on

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the 50th percentile of Rurine:serum) and Table S5 (based on the 25th, 75th and 95th

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percentiles of Rurine:serum) according to different Rurine:serum values. The median EDI of MeP was 126 μg/kg bw/day (Table 2), which was higher than the values previously

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reported for Chinese women (15.5 μg/kg bw/day) and the United States men and

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women (75.8 μg/kg bw/day) that derived from urinary concentrations (Ma et al., 2013). The median EDI of EtP (23.4 μg/kg bw/day) was higher than the values

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previously reported for Chinese women (2.5 μg/kg bw/day reported in Ma et al. (2013), and 0.67 μg/kg bw/day reported in Honda et al., (2018) and Korean women

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(7.97 μg/kg bw/day) (Honda et al., 2018). The median EDI of TCS was 49.5 μg/kg

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bw/day, higher than that reported for Greek women (2.4 μg/kg bw/day) (Asimakopoulos et al., 2014). The higher EDIs of parabens and TCS in our study may be due to the higher Rurine:serum values. Overall, the EDI values of parabens for pregnant women were 2-3 orders of magnitude lower than the acceptable daily intake (ADI, 1000 μg/kg bw/day) recommended by the European Food Safety Authority (EFSA, 2006). These results suggest that Chinese pregnant women are in a lower health risk from paraben exposure. We compared the geographical difference of EDIs for pregnant women from five regions of China, and found that the highest median EDIs of MeP and EtP were found both in pregnant women from the Northeast China (260 and 43.2 μg/kg bw/day). And the pregnant women from the North China had the highest median EDIs of TCS (51.5 μg/kg bw/day) (Table 2). Significant differences in EDIs were found for pregnant 12

Journal Pre-proof women from different regions in China (p<0.05). It was reported that Rurine:serum varied widely between different women (Hines et al., 2015). In order to describe the daily intakes more objectively, we calculated the EDIs under different Rurine:serum ratios (Table S5). When the Rurine:serum ratio was 177.5 or 376.4 (the 75th or 95th percentile), the calculated median EDIs of MeP and EtP were lower than the recommended ADI for parabens (1000 μg/kg bw/day; EFSA, 2006). However, the maximum EDIs of MeP, EtP and TCS exceeded the ADI value because of a higher value of R urine:serum (177.5 and 376.4). Although the median EDIs are not over the ADI value, health risks

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caused by intake of various parabens cannot be ignored. There are evidences that

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exposure to such chemicals may cause adverse health outcomes for humans, such as oxidative stress, DNA damage or thyroid hormones (Błędzka et al., 2014), especially

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for susceptible population such as pregnant women and fetuses (Watkins et al., 2015;

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Karwacka et al., 2019). Additionally, the fetuses may be exposed to parabens through

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growth.

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mother-to-fetus transfer, which brings potential health risks to their development and

4. Environmental implications

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We collected pregnant woman serum samples from 13 provinces in China and examined concentration profile and geographical distribution of parabens, TCC, and TCS. The baseline concentrations of these contaminants in pregnant woman serum were established nationwide. Further we attempted to evaluate the EDIs of such chemicals for pregnant women by using serum concentration, and adjusting the body weight of pregnant women instead of using average body weight of adult women. This would be more accurate in assessing real chemical exposure of pregnant woman, which can be used as a reference for pregnant woman exposure to other structurally similar chemicals. There are several limitations in our exposure calculation. First, due to restriction in sampling, the sample size for some regions is small. Further study needs to increase the sample size for investigation of the geographical distribution and corresponding human exposure to these contaminants. Second, some typical regions 13

Journal Pre-proof may be selected to estimate daily intake of chemicals from ingestion (diet), inhalation, and dermal absorption (for example, use of PCPs), which will give a more comprehensive view of human exposure. Third, the calculation of EDI based on Rurine:serum may be not very precise, as the Rurine:serum value is adopted from one previous study and studies are needed to provide a more suitable assumption of chemical concentration ratio between human urine and serum. Despite such limitations, our study provides a preliminary estimate in exposure of pregnant woman

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to several emerging contaminants.

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5. Conclusions

In summary, we detected 5 parabens (MeP, EtP, BuP, HeP and BzP) and 4 their

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metabolites (OH-MeP, OH-EtP, 4-HB and 3,4-DHB), and another two antibacterial

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agents (TCC and TCS) in pregnant woman serum samples from China. MeP, EtP,

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4-HB and TCS were the dominant compounds in serum, and their GM concentrations ranged from 0.239 to 211 ng/mL. Geographical differences in concentrations of these

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chemicals were observed in serum from five administrative regions, China. The median daily intakes of target analytes were estimated in the range of 23.4 (EtP) - 126

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(MeP) μg/kg bw/day, suggesting that the Chinese pregnant women were in a low health risk from exposure to such chemicals. To our knowledge, this is first report on concentration and geographical distribution of parabens, TCS and TCC in pregnant woman serum in China.

Declaration of interest The authors declare no conflicts of interest.

Acknowledgment This study was financially supported by National Natural Science Foundation of China (21806172 and 21677167), National Key Research and Development Program of China (2018YFC1801600), and the Thousand Young Talents Program of China. 14

Journal Pre-proof Appendix A. Supplementary data Supplementary

data

to

this

article

can

be

found

online

at

http://dx.doi.org/10.1016/j.scitotenv. xxx.

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Zhu, Q., Jia, J., Wang, Y., Zhang, K., Zhang, H., Liao, C., Jiang, G., 2019. Spatial distribution of parabens, triclocarban, triclosan, bisphenols, and

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tetrabromobisphenol A and its alternatives in municipal sewage sludges in China.

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Sci. Total Environ. 679, 61–69. https://doi.org/10.1016/j.scitotenv.2019.05.059

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Journal Pre-proof Table 1. Concentrations of parabens and their metabolites, TCC, and TCS in pregnant woman serum in China (n=162).

GMa

Median

Min

Max

DRb

MeP

1.86

3.08

0.130c

14.8

88.3%

EtP

0.239

0.327

0.020c

9.23

68.5%

BuP

0.014c

0.014c

0.014c

0.053

HeP

c

0.005

c

0.005

0.005

c

BzP

0.063c

0.063c

∑PBs

2.47

Paraben

0.6% 0.0%

0.063c

0.063c

0.0%

3.81

0.221

18.6

Paraben metabolite

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0.005

of

c

211

227

46.2

596

3,4-DHB

1.11c

1.11c

1.11c

1.11c

0.0%

OH-MeP

0.018c

0.018c

0.018c

0.046

1.90%

OH-EtP

0.018c

0.018c

0.018c

∑MBs

212

228

47.4

1.08

TCC

0.005c

0.005c

∑AAs

1.01

1.08

5.84

96.3%

0.005c

0.005c

0.0%

0.101

5.84

0.097c

0.018c 598

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a

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1.00

na

TCS

0.0%

lP

Antibacterial agent

100%

-p

4-HB

GM=geometric mean; bDR= detection rate; cValue= LOQ/√2 Target compounds with DR<50% were not discussed in the following sections.

23

Journal Pre-proof Table 2. Estimated daily intakes (EDIs, μg/kg bw/day) of select chemicals for pregnant woman in China (calculation based on Rurine:serum = 49 (the 50th percentile)). MeP

EtP

TCS

Median

126

23.4

49.5

Max

535

274

99.5

Median

99

15.3

51.5

Max

535

203

99.5

Median

260

43.2

42.2

Max

515

274

249

Median

22

1.0

4.0

Max

151

6.05

Median

134

7.2

45.4

Max

335

393

73.5

All (n=162)

of

North (n=88)

Max

48

0.985

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Median

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Southwest (n=8)

129

re 30.9

lP

Middle-south (n=19)

-p

East (n=28)

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Northeast (n=19)

48.5

43.3 67

24

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ro

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lP

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Figure 1. Geographical distribution of four dominant chemicals in serum from several provinces, China. * means significant differences in concentrations of these chemicals in serum from different regions (p<0.05). Numbers in parentheses represent sample size.

Figure 2. The correlations among chemical concentrations in serum in individual regions, *p<0.05, **p<0.01. Numbers in parentheses represent sample size.

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Graphic Abstract

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Declaration of interest

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The authors declare no conflicts of interest.

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Graphic Abstract

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Highlights: 

Parabens and their metabolites, TCS and TCC were measured in pregnant woman sera in China.



MeP, EtP, 4-HB and TCS were the predominant compounds in serum.



Geographical differences in serum concentrations of MeP, EtP, 4-HB and TCS were observed. Serum TCS concentrations were higher in old than young women.



Exposure to parabens and TCS poses low health risks to Chinese pregnant

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

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women.

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