{"paper_id":"4d2e7017-806b-49d8-af55-4c17fb2798fa","body_text":"Serum PBDEs exposure and influence factors in blood donors of Wuxi adults from 2013 to 2016 | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Serum PBDEs exposure and influence factors in blood donors of Wuxi adults from 2013 to 2016 Limei Chen, Qitao Yin, Lu Xu, Minyu Hua, Zhen Zhang, Yuqian Xu, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-2274407/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 14 Apr, 2023 Read the published version in Environmental Science and Pollution Research → Version 1 posted 5 You are reading this latest preprint version Abstract Polybrominated diphenyl ethers (PBDEs) have been used as brominated flame retardants worldwide and are correlated with extensive environmental pollution and human health concerns. This study aims to analyze the concentrations of PBDEs and to evaluate their temporal trends among a population of blood donors over a four-year period. Nine PBDE congeners were quantified in serum samples by gas chromatography with mass spectrometry (GC‒MS). The median concentrations of Σ 9 PBDEs in each year were 33.46, 29.75, 30.85 and 35.02 ng/g lipid, respectively. Most of the PBDE congeners showed a downward trend from 2013 to 2014 and then increased after 2014. No correlations between age and PBDE congener concentrations were observed, while concentrations of each congener and Σ 9 PBDE were nearly always lower in females than in males, especially in BDE-66, BDE-153, BDE-183, BDE-190 and Σ 9 PBDE. We also found that the intake of fish, fruit and eggs in the daily diet was related to the exposure level of PBDEs. Our results suggest that, as deca-BDE is still produced and used in China, diet is an important exposure pathway for PBDEs, and follow-up studies will be required to improve our understanding of the behaviors of PBDE isomers in humans and the exposure levels. Human biomonitoring Polybrominated diphenyl ethers Time trend Human serum Figures Figure 1 Figure 2 Figure 3 1. Introduction Polybrominated diphenyl ethers (PBDEs) are a group of 209 congeners and are used as brominated flame retardants (BFRs) to reduce flammability and the rate of ignition (Sjödin et al., 2019 ). In the past few decades, PBDEs have been widely used in electrical and electronic equipment, furniture and infant products. However, PBDEs are additive BFRs that volatilize or leach from products and cause serious pollution in the environment media and biota (Da et al., 2020 ; Liao et al., 2020 ; Hoang et al., 2020). Considering the extensive environmental pollution and human health concerns regarding the use of PBDEs, Stockholm Convention 2009 listed penta-BDE and octa-BDE as persistent organic pollutants (POPs) and entirely phased out their application. (Stockholm Convention on POPs, 2010). However, the production and application of deca-BDE (mainly composed of BDE-209) are retained in China (Zhao et al., 2020 ; Toms et al., 2018). On the other hand, even when PBDEs are withdrawn from the market, their release from existing products into the indoor environment as well as food may last for a long period of time. As a result, environmental and human exposure to PBDEs is inevitable at present and in the near future (Wu et al., 2020 ). PBDEs are lipophilic and are resistant to metabolism, which allows them to bioaccumulate in the liver and other fatty tissues. They have considerably long half-lives in human bodies, from 0.5 months to 6.5 years, as reported (Sjdin et al., 2020). Both epidemiological studies and animal experiments suggest that PBDEs exposure is associated with endocrine dysfunction, developmental neurotoxicity and reproductive toxicity (Ding et al., 2017 ; Chen et al., 2015 ; Ding et al., 2015 ; Sun et al., 2020 ; Kuriyama et al., 2005 ). Human biomonitoring is an important means to investigate human chemical pollutant exposure, which is useful in the assessment of time- or location-specific exposure trends and in identifying and investigating exposure in vulnerable groups (Knudsen et al., 2017). Despite the increasing evidence that PBDEs are associated with adverse health effects, there are no regulatory human exposure limits until now, which renders the importance of continuous biomonitoring of PBDEs using human blood serum samples. However, most of the continuous biomonitoring research on PBDEs has been conducted in Europe, North America and Australia, while very few Asian studies have been reported. Hurley et al. (2018) found statistically significant increases in the serum concentrations of all PBDEs among 1253 women over the four-year study period based on the California Teachers Study during 2011–2015. Ongoing temporal biomonitoring in the Australian population revealed that the lowest concentrations of PBDEs were detected in young children. In adults, concentrations of PBDEs congeners showed divergent temporal trends: BDE-47 and BDE-99 significantly declined over time, BDE-153 increased and BDE-100 remained the same over the study period (Toms et al., 2018). A study by Kim et al. ( 2018 ) observed a definite decline in PBDE levels in the Korean metropolitan population between 2001 and 2013. A study from China's BFR production area found that the levels of PBDEs in serum samples decreased between 2007 and 2013 (Li et al., 2017 ). However, considering the bioaccumulation and long half-life of PBDEs, as well as the fact that BDE209 is still produced and used in China, it is particularly important to explore the serum temporal trends of PBDEs in the Chinese population. The objective of the present study was to analyze the exposure trend and explore influential factors of PBDEs in blood donors in Wuxi from 2013 to 2016. The results will help to better understand the exposure levels and temporal changes of PBDEs in the population of Wuxi and improve public attention to brominated flame retardants (BFRs) in future surveys. 2. Material And Methods 2.1 Participants and recruitment Our study was performed in Wuxi, which is located in East China, southern Jiangsu Province, with the Yangtze River in the north and Taihu Lake in the south. Wuxi is a famous production base for textiles, clothing and electronic products in China, and BFRs are widely used in these fields. A total of 33 blood donors participated in this study. Each of the participants donated serum samples every year between 2013 and 2016, and the participants had lived in Wuxi for at least ten years. A specially trained investigator administered a 15-min questionnaire to the participants. The questionnaire included the following: demographic and socioeconomic information (age, height, weight, education level, household income) and the volunteer’s characteristics (occupation and the diet related habits). Information about the exposure to PBDEs was also contained in the questionnaire, including the donors’ occupation, whether there were any BFRs production factories near their home, and, if so, the types of BFRs produced. A daily diet including the intake of rice, noodles, eggs, milk, fish, meat, vegetables and fruits was also obtained along with a questionnaire survey of volunteers. All donors reported no chronic diseases, HIV infection or AIDS. Written informed consent was obtained from each participating donor. 2.2 Analysis of PBDEs and QA/QC All blood samples were aliquoted into 4-mL EDTA blood collection tubes. The serum was separated by centrifugation at 3000 rpm for 15 min and was then transferred into new tubes. The samples were transported to the laboratory and stored at − 20°C until they were analyzed. 1-mL serum samples per year were collected from each serum pool from each of the 33 blood donors. Analysis of PBDEs in serum samples was conducted using gas chromatography‒mass spectrometry (GC/MS). PBDE extraction and gravimetric lipid determination procedures have been previously published elsewhere (Hovander et al., 2000; Chen et al., 2018). Briefly, PBDEs were detected by GC/ECNI/MS on an Agilent 5975N mass spectrometer equipped with a 6890Gas Chromatograph. The identification of specific PBDEs was performed by comparing peak retention times with a standard solution containing nine identified tri-BDEs through octa-BDE congeners (BDE-28, -47, -66, -99, -100, -153, -154, -183 and − 190). The internal standard method ( 13 C 12 -BDE-139) is used to correct the error in the detection process. The limit of detection (LOD) is defined as concentrations greater than 3 S/N. Blank control experiments were carried out for each batch of samples, and the concentration of PBDEs in the blank samples were lower than LOD. The LOD ranged from 0.14 to 0.92 ng/g lipid in serum samples. 2.3 Statistical analysis Descriptive statistics were calculated for the demographic characteristics of donors. All congeners with detection frequencies over 70% were considered for the statistical analysis. An aggregate variable (sum of 9 congeners, ∑ 9 PBDE) was generated using the molar sum of these nine congeners. Summary statistics (including medians, minimum, and maximum values) were generated for the lipid-normalized concentration of each congener. For the purpose of statistical analyze, all samples found below the LOD were assigned as LOD/2 values. Initial evaluations of temporal trends were evaluated by plotting the concentration of each PBDE congener versus the year of sample collection. As the data were not normally distributed, relationships of the chemicals investigated with demographic characteristics and temporal trends between survey periods were examined using the Mann–Whitney U test or the Wilcoxon signed-rank test to determine statistically significant differences among categories of variables. All statistical tests were carried out using SPSS 22.0 software (IBM, Armonk, NY, USA) and GraphPad Prism. Statistical significance was determined at p < 0.05. 3. Results The data obtained from 33 blood donors (17 males and 16 females) were analyzed. Approximately two-thirds (22/33) of the donors were over 40 years old, 24 donors had a normal BMI (18.5–23 kg/m 2 ), 76.8% had graduated from high school or college, and 81.8% lived in households with a monthly income of less than RMB (¥) 10,000 Yuan. No one had access to PBDE exposure at work or lived adjacent to any BFR production factories. Detailed information on the sociodemographic characteristics of the donors in 2016 is shown in Table 1 . Serum concentrations of 9 PBDE congeners (BDE-28, BDE-47, BDE-66, BDE-99, BDE-100, BDE-153, BDE-154, BDE-183 and BDE-190) were measured. Table 2 shows the median concentration and range of all PBDE congeners in 132 serum samples collected from 33 blood donors between 2013 and 2016. The median concentrations of Σ 9 PBDEs in each year were 33.46, 29.75, 30.85 and 35.02 ng/g lipid, respectively. The range of concentrations of Σ 9 PBDEs each year was 12.89-100.06, 14.50-58.74, 11.22-105.77 and 11.37–172.10 ng/g lipid, respectively. BDE-190 was the most commonly detected congener with the highest levels, followed by BDE-28 and BDE-99. The distribution of the PBDE congeners in different years is summarized in Tables S1-S4 . All 9 PBDEs encompassing the four survey periods showed a U-shaped curve in concentration, except BDE-183 (Fig. 1 ). The p values for each Wilcoxon signed-rank test conducted between 2013 and 2016 are presented for each PBDE congener in the supporting information ( Tables S5-S13 ). In terms of age, there was no observed relationship between age and the concentration of PBDE congeners. Although not statistically significant, the Σ 9 PBDE concentrations of the 46–60 age group in all years except for 2014 were higher than those of the other two age groups (Fig. 2 .). Concentrations of each congener and Σ 9 PBDE were nearly always lower in females than in males (Table 3 , Fig. 3 ). BDE-66, BDE-153, BDE-183, BDE-190 and Σ 9 PBDE demonstrated a statistically significant difference (p < 0.05) between males (higher) and females (lower) in 2013 and 2016. When we analyzed the daily dietary and serum PBDE levels of the subjects, we found that the intake of eggs, catfish and grass carp in their daily diet was positively correlated with the exposure level of PBDEs, while the intake of fruits and bass was negatively correlated with the exposure level of PBDEs (Table 4 ). 4. Discussion Our study reported a four-year systematic biomonitoring of serum PBDE concentrations in the Wuxi blood donors. Although the present sample size is limited, instead of analyzing the pooled samples, we determined the donor’s serum individually each year to achieve our research objective, i.e., identifying relationships between serum concentrations of the target chemicals and donor ages, gender and daily diet, and explored the change in PBDEs during the investigation. At present, human serum is a crucial standard for estimating internal exposure to PBDEs and their associated health risks. The median Σ9PBDE concentrations (33.46–35.02 ng/g lipid from 2013 to 2016) in the present study are approximately 6 times higher than those reported in other studies performed in general populations in various areas of China, such as Dalian (median: age༜50, 5.08 ng/g lipid, age ≥ 50, 3.45 ng/g lipid) (Liu et al., 2017 ), Hong Kong (median: 5.36 ng/g, lw) (Wang et al., 2013), and Shanghai (median: 1.10 ng/g lw) (Xu et al., 2017). The levels in our study were also higher than those in studies performed in European countries such as the United Kingdom (median: 1.9 ng/g lipid) (Drage et al., 2019), Denmark (median: 7.7 ng/g lipid) (Vorkamp et al., 2014 ) and Norway (median: 2.3 ng/g lipid) (Cequier et al., 2015 ). On the other hand, the exposure level (except BDE-209) of our study population is similar to that of the general population in flame retardant production regions in China (21.68 ng/g lipid) (Chen et al., 2015 ). This is likely because our research site is a relatively developed industrial area with many textile and electronic product manufacturers that have added flame retardants more or less to the production process, which increases the risk of population exposure. Our study population had high exposure levels, but the geometric mean values of Σ 5 PBDEs across Northern California women were 51.6 ng/g lipid in 2011 and 43.6 ng/g lipid in 2014 (Parry et al., 2018 ). The different PBDE exposures are probably attributed to the disparate lifestyle and diet habits in different countries and cities (Akortia et al., 2016 , Wu et al., 2020 ). Several studies have shed light on the trend of PBDEs in human serum. For example, Toms et al. (2018) found that the exposure of PBDEs in young children in Australia decreased between the ten-year period 2002–2012 based on ongoing temporal monitoring. Drage et al. (2019) also found that PBDE levels in Australian children underwent a dramatic year-to-year decrease between 2006 and 2014. Based on the Korean metropolitan population, Kim et al. ( 2018 ) reported that PBDE levels declined between 2001 and 2013. In the PBDE production area in China, serum PBDEs also declined significantly between 2007 and 2013 (Li et al., 2017 ). Similar to the results of most studies, our research found that most PBDE congeners declined to varying degrees from 2013 to 2014. Decreasing concentrations of PBDEs are likely to be the result of a ban on the production and commercial use of penta-BDE since 2007, and the octa-BDE commercial product has never been produced in China (Ma et al., 2017). Nevertheless, our research indicated that the levels of PBDEs have increased again since 2014. A study by Hurley et al. ( 2017 ) also reported a statistically significant increase in PBDE serum levels in middle-aged and older California women from 2011 to 2015. Similarly, BDE-28 has been found to increase among Northern Californian pregnant women between 2008 and 2014 (Parry et al., 2018 ). No convincing explanation could be obtained according to the current data. We posit that the 2007 ban on penta- and octa-BDE in certain fields restrained PBDE exposure for a certain time. However, as deca-BDE was produced and used without any restrictive policy in 2008, population exposure to PBDEs unavoidably increased (Ji et al., 2017 ). In addition, a study also indicates that deca-BDE is likely to undergo rapid metabolism into low-brominated flame retardants such as penta- and octa-BDE in human bodies, which in turn increases the PBDE internal exposure. Our study population was 43.18 ± 8.48 years old on average (range: 26–56 years old), and approximately two-thirds (66.7%) of the donors were over 40 years old, while many other studies were conducted in much younger populations. An age-dependent increase in serum POPs levels has been documented in many studies (Jeon et al., 2021). Australian children’s serum samples collected by Drage et al. (2019) were found a positive association between BDE-47 levels and age (R = 0.41, p = 0.008). Hurley et al. ( 2017 ) also found that older adults had higher PBDE concentrations. Sjodin et al. (2008) analyzed the serum samples of participants over 12 years old for PBDEs in the National Health and Nutrition Examination Survey (NHANES) 2003–2004, stratified and regression analyses were used to examine levels among demographic groups. They found that PBDE concentrations showed both a linear decrease and a positive quadratic trend with age. To date, few studies have explored the relationship between the pharmacokinetics of PBDEs and age as well as other physiological reasons. Our study found that the Σ 9 PBDE concentrations of the 46–60 age population were higher than those of the other two younger groups in all years except 2014. In addition, an increase in half-life with age and an aging-related reduction in the elimination rate could be one of the possible reasons for the age-related increase in POPs in humans (Hardell et al., 2010; Porta et al., 2012). We also found that PBDEs were sex- and congener-specific in our study population. Levels of PBDEs were nearly always lower in females than in males. When stratified by sex, BDE-66, BDE-153, BDE-183, BDE-190 and Σ 9 PBDE demonstrated a statistically significant difference (p < 0.05) between males (higher) and females (lower) in 2013 and 2016. Similar results regarding Σ 5 PBDE levels were also found in New Zealand (Coakley et al., 2018 ). Toms et al. (2018) also analyzed PBDE exposure in an Australian population and found that the levels of BDE-47, BDE-99, BDE-100, BDE-153 and Σ 4 PBDE were lower in adult females (aged 31–45) than in males from 2002–2012. One potential explanation may lie in the females' regular menses, which contribute to the excretion of most of the POPs. On the other hand, women tend to have more body fat distribution than men. As PBDEs are lipophilic, they are more inclined to distribute in body fat than in serum, resulting in lower serum levels of PBDEs in females than in males. In addition, lactating women may excrete some PBDEs through breastfeeding, although further proof is needed. This also reminds us of the exposure risk of children to PBDEs, although it is not discussed in this text. PBDEs are a type of POPs that accumulate in organisms and are biomagnified through food chains with elevated levels in top predators (Moon et al. 2010 ). Previous studies have revealed that lipid-rich foods such as eggs, meat and dairy products contribute significantly to human exposure to PBDEs. We found that the intake of eggs, grass carp and catfish in the daily diet of blood donors was positively correlated with PBDEs. Consistent with our research, Chen et al. (2014) found that dietary exposure in their study was a significant route of human PBDE intake and was largely attributed to the consumption of aquatic foods. A study in Korean seafood between 2005 and 2017 also found elevated PBDE concentrations in fatty fish, such as herring, mackerel, and tuna (Choi et al., 2021). This may be because fatty fish are at the upper layer of the food chain, which easily produces a bioamplification effect and causes PBDEs to accumulate in the external environment, thus entering the human body. On the other hand, we also found that daily fruit intake was negatively correlated with PBDE levels. One possibility is that due to lipophilicity, bioaccumulation and biomagnification, PBDEs may accumulate in animals through the food chain, while plants accumulate it to a lesser extent. Most temporal trend studies are performed on samples from different individuals from different years or using pooled samples, which might obscure the variation between individuals and accordingly the temporal trend. To the best of our knowledge, we were the first study that actually able to follow the same donor’s serum PBDEs concentrations over a 4-year period. However, several limitations and considerations apply to the evaluation of our present study. First, BDE-209 was not detected in our study, which is one of the main BFRs still being produced and widely used in China. Therefore, we are unable to obtain the exposure trend of BDE-209 in recent years. Second, we only analyzed 132 serum samples collected from 33 donors (repeated sampling of the same individuals over the last 4 years), and the small sample size may limit our power to detect a significant trend over time. 5. Conclusion Our present study focused on determining the levels of 9 PBDE congeners in individual serum samples collected from 2013 to 2016 from blood donors in the Wuxi area. Based on these results, an overall temporal PBDE trend was observed, demonstrating that PBDE levels in the Wuxi area declined between 2013 and 2014 and then increased again after 2014. We also found that PBDEs were sex- and congener-specific in our study population, especially BDE-66, BDE-153, BDE-183, BDE-190 and Σ 9 PBDE. Moreover, we found that daily dietary intake was related to PBDE exposure. One aspect PBDE congeners are very persistent in the environment and in biota and may negatively affect human health, what is worse, as deca-BDE is still produced and used in China, follow-up studies will be required to improve our understanding of the behaviors of PBDE isomers in humans and the exposure levels. Declarations Acknowledgments We acknowledge the participants for providing serum samples, the staff of Blood Centre for collecting and saving biological samples, and the research team for collecting and analyzing the data. Founding This research was supported by the National Natural Science Foundation of China (Grant No. 81803199), the Project of Wuxi Commission of Health, China (Grant No. Z201813) and the Medical Key Discipline Program of Wuxi Health Commission (LCZX2021006). Competing Interests The authors have no relevant financial or non-financial interests to disclose. Author Contributions All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Limei Chen, Qitao Yin, Lu Xu, Lu Xu, Minyu Hua, Zhen Zhang, Yuqian Xu, Wei Xia, Huizhong Qian, Jun Hong and Jun Jin. The first draft of the manuscript was written by Limei Chen and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript. The authors have no conflicts of interest to declare. References Akortia E, Okonkwo J, Lupankwa M, et al. A review of sources, levels, and toxicity of polybrominated diphenyl ethers (PBDEs) and their transformation and transport in various environmental compartments. Environmental Reviews, 2016, 24(3). Cequier E, RM Marcé, Becher G, et al. Comparing human exposure to emerging and legacy flame retardants from the indoor environment and diet with concentrations measured in serum. Environment International, 2015, 74(jan.):54-59. Chen L, Wang C, Cui C, et al. Prenatal exposure to polybrominated diphenyl ethers and birth outcomes. 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Supplementary Files Tables.docx Supplementarymaterials.docx Cite Share Download PDF Status: Published Journal Publication published 14 Apr, 2023 Read the published version in Environmental Science and Pollution Research → Version 1 posted Reviewers agreed at journal 11 Jan, 2023 Reviewers invited by journal 11 Jan, 2023 Editor invited by journal 03 Jan, 2023 Editor assigned by journal 08 Dec, 2022 First submitted to journal 05 Dec, 2022 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {\"props\":{\"pageProps\":{\"initialData\":{\"identity\":\"rs-2274407\",\"acceptedTermsAndConditions\":true,\"allowDirectSubmit\":false,\"archivedVersions\":[],\"articleType\":\"Research Article\",\"associatedPublications\":[],\"authors\":[{\"id\":166816228,\"identity\":\"166c3fd2-8a39-40ae-98e1-bea1f1b9fcc8\",\"order_by\":0,\"name\":\"Limei Chen\",\"email\":\"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA4UlEQVRIiWNgGAWjYDACCSB+YMDAwMbe2Pjgg4GNHXFaEkBaeA43G84oSEsmUguYkd4mzfPhEGMDIR38s5uPPUgo2CbHJ5HYJm1jcICZgf3w0Q14LblzLN0gweC2MRvPw2brHIM7fAw8aWk38GkxkMgxkwBqSWxjT2y8nWPwjJlBgseMgJb8byAt9W0MiQ3SFgaHGRsIa8lhA2lJYONIbJJmIEaLxI00sMMM23gONhv2GKQlsxHyC/+M5GcSH/7clpdvb3/44McfGzt+9sPH8GrBBGykKR8Fo2AUjIJRgA0AAHs/SeSJSx20AAAAAElFTkSuQmCC\",\"orcid\":\"https://orcid.org/0000-0002-0934-9896\",\"institution\":\"Wuxi Center for Disease Control and Prevention\",\"correspondingAuthor\":true,\"prefix\":\"\",\"firstName\":\"Limei\",\"middleName\":\"\",\"lastName\":\"Chen\",\"suffix\":\"\"},{\"id\":166816229,\"identity\":\"9787fc3a-8f99-4645-9282-7566bd52ea4d\",\"order_by\":1,\"name\":\"Qitao Yin\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Wuxi Maternity and Child Health Care Hospital\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Qitao\",\"middleName\":\"\",\"lastName\":\"Yin\",\"suffix\":\"\"},{\"id\":166816230,\"identity\":\"0aad6d4d-d229-4015-ac59-b748a57905b1\",\"order_by\":2,\"name\":\"Lu Xu\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Wuxi Blood Center\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Lu\",\"middleName\":\"\",\"lastName\":\"Xu\",\"suffix\":\"\"},{\"id\":166816231,\"identity\":\"d01c9de1-bd4f-4fe1-a26c-a613657cfbd0\",\"order_by\":3,\"name\":\"Minyu Hua\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Wuxi Blood Center\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Minyu\",\"middleName\":\"\",\"lastName\":\"Hua\",\"suffix\":\"\"},{\"id\":166816232,\"identity\":\"2cf7635b-0b7d-4b89-91bb-ed7ec04866e6\",\"order_by\":4,\"name\":\"Zhen Zhang\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Wuxi Blood Center\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Zhen\",\"middleName\":\"\",\"lastName\":\"Zhang\",\"suffix\":\"\"},{\"id\":166816233,\"identity\":\"baaa6dab-c7f7-4906-a658-e0412249c1e6\",\"order_by\":5,\"name\":\"Yuqian Xu\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Wuxi Blood Center\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Yuqian\",\"middleName\":\"\",\"lastName\":\"Xu\",\"suffix\":\"\"},{\"id\":166816234,\"identity\":\"3423e571-6dc6-4b41-9b54-96e27b9178c9\",\"order_by\":6,\"name\":\"Wei Xia\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Wuxi Blood Center\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Wei\",\"middleName\":\"\",\"lastName\":\"Xia\",\"suffix\":\"\"},{\"id\":166816235,\"identity\":\"03937734-3016-4b8c-bf4a-d4f6847e3c26\",\"order_by\":7,\"name\":\"Huizhong Qian\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Wuxi Blood Center\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Huizhong\",\"middleName\":\"\",\"lastName\":\"Qian\",\"suffix\":\"\"},{\"id\":166816236,\"identity\":\"715bf7b9-feed-4563-9bf6-b973eec62962\",\"order_by\":8,\"name\":\"Jun Hong\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Wuxi Blood Center\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Jun\",\"middleName\":\"\",\"lastName\":\"Hong\",\"suffix\":\"\"},{\"id\":166816237,\"identity\":\"52668818-595c-4a4b-82b4-b36f4b00530f\",\"order_by\":9,\"name\":\"Jun Jin\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Minzu University of China\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Jun\",\"middleName\":\"\",\"lastName\":\"Jin\",\"suffix\":\"\"}],\"badges\":[],\"createdAt\":\"2022-11-15 05:06:31\",\"currentVersionCode\":1,\"declarations\":\"\",\"doi\":\"10.21203/rs.3.rs-2274407/v1\",\"doiUrl\":\"https://doi.org/10.21203/rs.3.rs-2274407/v1\",\"draftVersion\":[],\"editorialEvents\":[{\"content\":\"https://doi.org/10.1007/s11356-023-26802-y\",\"type\":\"published\",\"date\":\"2023-04-14T20:26:41+00:00\"}],\"editorialNote\":\"\",\"failedWorkflow\":false,\"files\":[{\"id\":31557717,\"identity\":\"57a4d3eb-ece8-4fb2-b3bc-6a37fac6b01a\",\"added_by\":\"auto\",\"created_at\":\"2023-01-13 20:43:18\",\"extension\":\"png\",\"order_by\":1,\"title\":\"Figure 1\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":27602,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003eChange curve of BDE congeners’ concentrations from 2013 to 2016. (A) The change curve of BDE congeners except BDE-183. (B) Change curve of BDE-183 during 2013 and 2016.\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"Onlinefloatimage1.png\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-2274407/v1/2a487b8bd23cd2ad6cbd279a.png\"},{\"id\":31557152,\"identity\":\"9ebb0b1b-f373-4ae4-ac29-3c22b993d3a0\",\"added_by\":\"auto\",\"created_at\":\"2023-01-13 20:35:18\",\"extension\":\"png\",\"order_by\":2,\"title\":\"Figure 2\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":46741,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003eArithmetic means and standard errors for ∑\\u003csub\\u003e9\\u003c/sub\\u003ePBDEs by age group and sample collection year.\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"2.png\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-2274407/v1/cdfda6ca6d2a811d6abc5fc8.png\"},{\"id\":31557149,\"identity\":\"2fe6b623-8a44-41c4-bf5b-2a08a07f0916\",\"added_by\":\"auto\",\"created_at\":\"2023-01-13 20:35:17\",\"extension\":\"png\",\"order_by\":3,\"title\":\"Figure 3\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":46817,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003eMedian and Range for ∑\\u003csub\\u003e9\\u003c/sub\\u003ePBDEs in males and females.\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"3.png\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-2274407/v1/f525e788ec3059b5ab712011.png\"},{\"id\":44725268,\"identity\":\"ec9cab5a-b6d1-4ab7-be7a-df3463276871\",\"added_by\":\"auto\",\"created_at\":\"2023-10-16 20:40:03\",\"extension\":\"pdf\",\"order_by\":0,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"manuscript-pdf\",\"size\":433579,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"manuscript.pdf\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-2274407/v1/d658d052-841a-4c12-b212-624a23faf98c.pdf\"},{\"id\":31557148,\"identity\":\"816ae8a6-ac27-492c-9585-11f708e48a0e\",\"added_by\":\"auto\",\"created_at\":\"2023-01-13 20:35:17\",\"extension\":\"docx\",\"order_by\":1,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"supplement\",\"size\":59670,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"Tables.docx\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-2274407/v1/9e764e6cad1336e7458eb6ef.docx\"},{\"id\":31557151,\"identity\":\"a0b6bab8-85e6-40ae-b797-27e0226d3939\",\"added_by\":\"auto\",\"created_at\":\"2023-01-13 20:35:18\",\"extension\":\"docx\",\"order_by\":2,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"supplement\",\"size\":28334,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"Supplementarymaterials.docx\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-2274407/v1/1ed2402cdd996b36fed5417c.docx\"}],\"financialInterests\":\"\",\"formattedTitle\":\"Serum PBDEs exposure and influence factors in blood donors of Wuxi adults from 2013 to 2016\",\"fulltext\":[{\"header\":\"1. Introduction\",\"content\":\"\\u003cp\\u003ePolybrominated diphenyl ethers (PBDEs) are a group of 209 congeners and are used as brominated flame retardants (BFRs) to reduce flammability and the rate of ignition (Sj\\u0026ouml;din et al., \\u003cspan citationid=\\\"CR28\\\" class=\\\"CitationRef\\\"\\u003e2019\\u003c/span\\u003e). In the past few decades, PBDEs have been widely used in electrical and electronic equipment, furniture and infant products. However, PBDEs are additive BFRs that volatilize or leach from products and cause serious pollution in the environment media and biota (Da et al., \\u003cspan citationid=\\\"CR7\\\" class=\\\"CitationRef\\\"\\u003e2020\\u003c/span\\u003e; Liao et al., \\u003cspan citationid=\\\"CR21\\\" class=\\\"CitationRef\\\"\\u003e2020\\u003c/span\\u003e; Hoang et al., 2020). Considering the extensive environmental pollution and human health concerns regarding the use of PBDEs, Stockholm Convention 2009 listed penta-BDE and octa-BDE as persistent organic pollutants (POPs) and entirely phased out their application. (Stockholm Convention on POPs, 2010). However, the production and application of deca-BDE (mainly composed of BDE-209) are retained in China (Zhao et al., \\u003cspan citationid=\\\"CR39\\\" class=\\\"CitationRef\\\"\\u003e2020\\u003c/span\\u003e; Toms et al., 2018). On the other hand, even when PBDEs are withdrawn from the market, their release from existing products into the indoor environment as well as food may last for a long period of time. As a result, environmental and human exposure to PBDEs is inevitable at present and in the near future (Wu et al., \\u003cspan citationid=\\\"CR40\\\" class=\\\"CitationRef\\\"\\u003e2020\\u003c/span\\u003e).\\u003c/p\\u003e \\u003cp\\u003ePBDEs are lipophilic and are resistant to metabolism, which allows them to bioaccumulate in the liver and other fatty tissues. They have considerably long half-lives in human bodies, from 0.5 months to 6.5 years, as reported (Sjdin et al., 2020). Both epidemiological studies and animal experiments suggest that PBDEs exposure is associated with endocrine dysfunction, developmental neurotoxicity and reproductive toxicity (Ding et al., \\u003cspan citationid=\\\"CR8\\\" class=\\\"CitationRef\\\"\\u003e2017\\u003c/span\\u003e; Chen et al., \\u003cspan citationid=\\\"CR3\\\" class=\\\"CitationRef\\\"\\u003e2015\\u003c/span\\u003e; Ding et al., \\u003cspan citationid=\\\"CR9\\\" class=\\\"CitationRef\\\"\\u003e2015\\u003c/span\\u003e; Sun et al., \\u003cspan citationid=\\\"CR32\\\" class=\\\"CitationRef\\\"\\u003e2020\\u003c/span\\u003e; Kuriyama et al., \\u003cspan citationid=\\\"CR17\\\" class=\\\"CitationRef\\\"\\u003e2005\\u003c/span\\u003e).\\u003c/p\\u003e \\u003cp\\u003eHuman biomonitoring is an important means to investigate human chemical pollutant exposure, which is useful in the assessment of time- or location-specific exposure trends and in identifying and investigating exposure in vulnerable groups (Knudsen et al., 2017). Despite the increasing evidence that PBDEs are associated with adverse health effects, there are no regulatory human exposure limits until now, which renders the importance of continuous biomonitoring of PBDEs using human blood serum samples. However, most of the continuous biomonitoring research on PBDEs has been conducted in Europe, North America and Australia, while very few Asian studies have been reported. Hurley et al. (2018) found statistically significant increases in the serum concentrations of all PBDEs among 1253 women over the four-year study period based on the California Teachers Study during 2011\\u0026ndash;2015. Ongoing temporal biomonitoring in the Australian population revealed that the lowest concentrations of PBDEs were detected in young children. In adults, concentrations of PBDEs congeners showed divergent temporal trends: BDE-47 and BDE-99 significantly declined over time, BDE-153 increased and BDE-100 remained the same over the study period (Toms et al., 2018). A study by Kim et al. (\\u003cspan citationid=\\\"CR18\\\" class=\\\"CitationRef\\\"\\u003e2018\\u003c/span\\u003e) observed a definite decline in PBDE levels in the Korean metropolitan population between 2001 and 2013. A study from China's BFR production area found that the levels of PBDEs in serum samples decreased between 2007 and 2013 (Li et al., \\u003cspan citationid=\\\"CR22\\\" class=\\\"CitationRef\\\"\\u003e2017\\u003c/span\\u003e). However, considering the bioaccumulation and long half-life of PBDEs, as well as the fact that BDE209 is still produced and used in China, it is particularly important to explore the serum temporal trends of PBDEs in the Chinese population.\\u003c/p\\u003e \\u003cp\\u003eThe objective of the present study was to analyze the exposure trend and explore influential factors of PBDEs in blood donors in Wuxi from 2013 to 2016. The results will help to better understand the exposure levels and temporal changes of PBDEs in the population of Wuxi and improve public attention to brominated flame retardants (BFRs) in future surveys.\\u003c/p\\u003e\"},{\"header\":\"2. Material And Methods\",\"content\":\"\\u003cdiv id=\\\"Sec3\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003e2.1 Participants and recruitment\\u003c/h2\\u003e \\u003cp\\u003eOur study was performed in Wuxi, which is located in East China, southern Jiangsu Province, with the Yangtze River in the north and Taihu Lake in the south. Wuxi is a famous production base for textiles, clothing and electronic products in China, and BFRs are widely used in these fields. A total of 33 blood donors participated in this study. Each of the participants donated serum samples every year between 2013 and 2016, and the participants had lived in Wuxi for at least ten years. A specially trained investigator administered a 15-min questionnaire to the participants. The questionnaire included the following: demographic and socioeconomic information (age, height, weight, education level, household income) and the volunteer\\u0026rsquo;s characteristics (occupation and the diet related habits). Information about the exposure to PBDEs was also contained in the questionnaire, including the donors\\u0026rsquo; occupation, whether there were any BFRs production factories near their home, and, if so, the types of BFRs produced. A daily diet including the intake of rice, noodles, eggs, milk, fish, meat, vegetables and fruits was also obtained along with a questionnaire survey of volunteers. All donors reported no chronic diseases, HIV infection or AIDS. Written informed consent was obtained from each participating donor.\\u003c/p\\u003e \\u003c/div\\u003e \\u003cdiv id=\\\"Sec4\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003e2.2 Analysis of PBDEs and QA/QC\\u003c/h2\\u003e \\u003cp\\u003eAll blood samples were aliquoted into 4-mL EDTA blood collection tubes. The serum was separated by centrifugation at 3000 rpm for 15 min and was then transferred into new tubes. The samples were transported to the laboratory and stored at \\u0026minus;\\u0026thinsp;20\\u0026deg;C until they were analyzed. 1-mL serum samples per year were collected from each serum pool from each of the 33 blood donors. Analysis of PBDEs in serum samples was conducted using gas chromatography‒mass spectrometry (GC/MS).\\u003c/p\\u003e \\u003cp\\u003ePBDE extraction and gravimetric lipid determination procedures have been previously published elsewhere (Hovander et al., 2000; Chen et al., 2018). Briefly, PBDEs were detected by GC/ECNI/MS on an Agilent 5975N mass spectrometer equipped with a 6890Gas Chromatograph. The identification of specific PBDEs was performed by comparing peak retention times with a standard solution containing nine identified tri-BDEs through octa-BDE congeners (BDE-28, -47, -66, -99, -100, -153, -154, -183 and \\u0026minus;\\u0026thinsp;190). The internal standard method (\\u003csup\\u003e13\\u003c/sup\\u003eC\\u003csub\\u003e12\\u003c/sub\\u003e-BDE-139) is used to correct the error in the detection process. The limit of detection (LOD) is defined as concentrations greater than 3 S/N. Blank control experiments were carried out for each batch of samples, and the concentration of PBDEs in the blank samples were lower than LOD. The LOD ranged from 0.14 to 0.92 ng/g lipid in serum samples.\\u003c/p\\u003e \\u003c/div\\u003e \\u003cdiv id=\\\"Sec5\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003e2.3 Statistical analysis\\u003c/h2\\u003e \\u003cp\\u003eDescriptive statistics were calculated for the demographic characteristics of donors. All congeners with detection frequencies over 70% were considered for the statistical analysis. An aggregate variable (sum of 9 congeners, \\u0026sum;\\u003csub\\u003e9\\u003c/sub\\u003ePBDE) was generated using the molar sum of these nine congeners. Summary statistics (including medians, minimum, and maximum values) were generated for the lipid-normalized concentration of each congener. For the purpose of statistical analyze, all samples found below the LOD were assigned as LOD/2 values.\\u003c/p\\u003e \\u003cp\\u003eInitial evaluations of temporal trends were evaluated by plotting the concentration of each PBDE congener versus the year of sample collection. As the data were not normally distributed, relationships of the chemicals investigated with demographic characteristics and temporal trends between survey periods were examined using the Mann\\u0026ndash;Whitney U test or the Wilcoxon signed-rank test to determine statistically significant differences among categories of variables. All statistical tests were carried out using SPSS 22.0 software (IBM, Armonk, NY, USA) and GraphPad Prism. Statistical significance was determined at p\\u0026thinsp;\\u0026lt;\\u0026thinsp;0.05.\\u003c/p\\u003e \\u003c/div\\u003e\"},{\"header\":\"3. Results\",\"content\":\"\\u003cp\\u003eThe data obtained from 33 blood donors (17 males and 16 females) were analyzed. Approximately two-thirds (22/33) of the donors were over 40 years old, 24 donors had a normal BMI (18.5\\u0026ndash;23 kg/m\\u003csup\\u003e2\\u003c/sup\\u003e), 76.8% had graduated from high school or college, and 81.8% lived in households with a monthly income of less than RMB (\\u0026yen;) 10,000 Yuan. No one had access to PBDE exposure at work or lived adjacent to any BFR production factories. Detailed information on the sociodemographic characteristics of the donors in 2016 is shown in Table \\u003cspan class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003e.\\u003c/p\\u003e\\n\\u003cp\\u003eSerum concentrations of 9 PBDE congeners (BDE-28, BDE-47, BDE-66, BDE-99, BDE-100, BDE-153, BDE-154, BDE-183 and BDE-190) were measured. Table \\u003cspan class=\\\"InternalRef\\\"\\u003e2\\u003c/span\\u003e shows the median concentration and range of all PBDE congeners in 132 serum samples collected from 33 blood donors between 2013 and 2016. The median concentrations of \\u0026Sigma;\\u003csub\\u003e9\\u003c/sub\\u003ePBDEs in each year were 33.46, 29.75, 30.85 and 35.02 ng/g lipid, respectively. The range of concentrations of \\u0026Sigma;\\u003csub\\u003e9\\u003c/sub\\u003ePBDEs each year was 12.89-100.06, 14.50-58.74, 11.22-105.77 and 11.37\\u0026ndash;172.10 ng/g lipid, respectively. BDE-190 was the most commonly detected congener with the highest levels, followed by BDE-28 and BDE-99. The distribution of the PBDE congeners in different years is summarized in \\u003cstrong\\u003eTables S1-S4\\u003c/strong\\u003e.\\u003c/p\\u003e\\n\\u003cp\\u003eAll 9 PBDEs encompassing the four survey periods showed a U-shaped curve in concentration, except BDE-183 (Fig. \\u003cspan class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003e). The p values for each Wilcoxon signed-rank test conducted between 2013 and 2016 are presented for each PBDE congener in the supporting information (\\u003cstrong\\u003eTables S5-S13\\u003c/strong\\u003e). In terms of age, there was no observed relationship between age and the concentration of PBDE congeners. Although not statistically significant, the \\u0026Sigma;\\u003csub\\u003e9\\u003c/sub\\u003ePBDE concentrations of the 46\\u0026ndash;60 age group in all years except for 2014 were higher than those of the other two age groups (Fig. \\u003cspan class=\\\"InternalRef\\\"\\u003e2\\u003c/span\\u003e.). Concentrations of each congener and \\u0026Sigma;\\u003csub\\u003e9\\u003c/sub\\u003ePBDE were nearly always lower in females than in males (Table \\u003cspan class=\\\"InternalRef\\\"\\u003e3\\u003c/span\\u003e, Fig. \\u003cspan class=\\\"InternalRef\\\"\\u003e3\\u003c/span\\u003e). BDE-66, BDE-153, BDE-183, BDE-190 and \\u0026Sigma;\\u003csub\\u003e9\\u003c/sub\\u003ePBDE demonstrated a statistically significant difference (p\\u0026thinsp;\\u0026lt;\\u0026thinsp;0.05) between males (higher) and females (lower) in 2013 and 2016.\\u003c/p\\u003e\\n\\u003cp\\u003eWhen we analyzed the daily dietary and serum PBDE levels of the subjects, we found that the intake of eggs, catfish and grass carp in their daily diet was positively correlated with the exposure level of PBDEs, while the intake of fruits and bass was negatively correlated with the exposure level of PBDEs (Table \\u003cspan class=\\\"InternalRef\\\"\\u003e4\\u003c/span\\u003e).\\u003c/p\\u003e\"},{\"header\":\"4. Discussion\",\"content\":\"\\u003cp\\u003eOur study reported a four-year systematic biomonitoring of serum PBDE concentrations in the Wuxi blood donors. Although the present sample size is limited, instead of analyzing the pooled samples, we determined the donor\\u0026rsquo;s serum individually each year to achieve our research objective, i.e., identifying relationships between serum concentrations of the target chemicals and donor ages, gender and daily diet, and explored the change in PBDEs during the investigation.\\u003c/p\\u003e \\u003cp\\u003eAt present, human serum is a crucial standard for estimating internal exposure to PBDEs and their associated health risks. The median Σ9PBDE concentrations (33.46\\u0026ndash;35.02 ng/g lipid from 2013 to 2016) in the present study are approximately 6 times higher than those reported in other studies performed in general populations in various areas of China, such as Dalian (median: age༜50, 5.08 ng/g lipid, age\\u0026thinsp;\\u0026ge;\\u0026thinsp;50, 3.45 ng/g lipid) (Liu et al., \\u003cspan citationid=\\\"CR20\\\" class=\\\"CitationRef\\\"\\u003e2017\\u003c/span\\u003e), Hong Kong (median: 5.36 ng/g, lw) (Wang et al., 2013), and Shanghai (median: 1.10 ng/g lw) (Xu et al., 2017). The levels in our study were also higher than those in studies performed in European countries such as the United Kingdom (median: 1.9 ng/g lipid) (Drage et al., 2019), Denmark (median: 7.7 ng/g lipid) (Vorkamp et al., \\u003cspan citationid=\\\"CR34\\\" class=\\\"CitationRef\\\"\\u003e2014\\u003c/span\\u003e) and Norway (median: 2.3 ng/g lipid) (Cequier et al., \\u003cspan citationid=\\\"CR2\\\" class=\\\"CitationRef\\\"\\u003e2015\\u003c/span\\u003e). On the other hand, the exposure level (except BDE-209) of our study population is similar to that of the general population in flame retardant production regions in China (21.68 ng/g lipid) (Chen et al., \\u003cspan citationid=\\\"CR3\\\" class=\\\"CitationRef\\\"\\u003e2015\\u003c/span\\u003e). This is likely because our research site is a relatively developed industrial area with many textile and electronic product manufacturers that have added flame retardants more or less to the production process, which increases the risk of population exposure. Our study population had high exposure levels, but the geometric mean values of Σ\\u003csub\\u003e5\\u003c/sub\\u003ePBDEs across Northern California women were 51.6 ng/g lipid in 2011 and 43.6 ng/g lipid in 2014 (Parry et al., \\u003cspan citationid=\\\"CR26\\\" class=\\\"CitationRef\\\"\\u003e2018\\u003c/span\\u003e). The different PBDE exposures are probably attributed to the disparate lifestyle and diet habits in different countries and cities (Akortia et al., \\u003cspan citationid=\\\"CR1\\\" class=\\\"CitationRef\\\"\\u003e2016\\u003c/span\\u003e, Wu et al., \\u003cspan citationid=\\\"CR40\\\" class=\\\"CitationRef\\\"\\u003e2020\\u003c/span\\u003e).\\u003c/p\\u003e \\u003cp\\u003eSeveral studies have shed light on the trend of PBDEs in human serum. For example, Toms et al. (2018) found that the exposure of PBDEs in young children in Australia decreased between the ten-year period 2002\\u0026ndash;2012 based on ongoing temporal monitoring. Drage et al. (2019) also found that PBDE levels in Australian children underwent a dramatic year-to-year decrease between 2006 and 2014. Based on the Korean metropolitan population, Kim et al. (\\u003cspan citationid=\\\"CR18\\\" class=\\\"CitationRef\\\"\\u003e2018\\u003c/span\\u003e) reported that PBDE levels declined between 2001 and 2013. In the PBDE production area in China, serum PBDEs also declined significantly between 2007 and 2013 (Li et al., \\u003cspan citationid=\\\"CR22\\\" class=\\\"CitationRef\\\"\\u003e2017\\u003c/span\\u003e). Similar to the results of most studies, our research found that most PBDE congeners declined to varying degrees from 2013 to 2014. Decreasing concentrations of PBDEs are likely to be the result of a ban on the production and commercial use of penta-BDE since 2007, and the octa-BDE commercial product has never been produced in China (Ma et al., 2017). Nevertheless, our research indicated that the levels of PBDEs have increased again since 2014. A study by Hurley et al. (\\u003cspan citationid=\\\"CR13\\\" class=\\\"CitationRef\\\"\\u003e2017\\u003c/span\\u003e) also reported a statistically significant increase in PBDE serum levels in middle-aged and older California women from 2011 to 2015. Similarly, BDE-28 has been found to increase among Northern Californian pregnant women between 2008 and 2014 (Parry et al., \\u003cspan citationid=\\\"CR26\\\" class=\\\"CitationRef\\\"\\u003e2018\\u003c/span\\u003e). No convincing explanation could be obtained according to the current data. We posit that the 2007 ban on penta- and octa-BDE in certain fields restrained PBDE exposure for a certain time. However, as deca-BDE was produced and used without any restrictive policy in 2008, population exposure to PBDEs unavoidably increased (Ji et al., \\u003cspan citationid=\\\"CR15\\\" class=\\\"CitationRef\\\"\\u003e2017\\u003c/span\\u003e). In addition, a study also indicates that deca-BDE is likely to undergo rapid metabolism into low-brominated flame retardants such as penta- and octa-BDE in human bodies, which in turn increases the PBDE internal exposure.\\u003c/p\\u003e \\u003cp\\u003eOur study population was 43.18\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;8.48 years old on average (range: 26\\u0026ndash;56 years old), and approximately two-thirds (66.7%) of the donors were over 40 years old, while many other studies were conducted in much younger populations. An age-dependent increase in serum POPs levels has been documented in many studies (Jeon et al., 2021). Australian children\\u0026rsquo;s serum samples collected by Drage et al. (2019) were found a positive association between BDE-47 levels and age (R\\u0026thinsp;=\\u0026thinsp;0.41, p\\u0026thinsp;=\\u0026thinsp;0.008). Hurley et al. (\\u003cspan citationid=\\\"CR13\\\" class=\\\"CitationRef\\\"\\u003e2017\\u003c/span\\u003e) also found that older adults had higher PBDE concentrations. Sjodin et al. (2008) analyzed the serum samples of participants over 12 years old for PBDEs in the National Health and Nutrition Examination Survey (NHANES) 2003\\u0026ndash;2004, stratified and regression analyses were used to examine levels among demographic groups. They found that PBDE concentrations showed both a linear decrease and a positive quadratic trend with age. To date, few studies have explored the relationship between the pharmacokinetics of PBDEs and age as well as other physiological reasons. Our study found that the Σ\\u003csub\\u003e9\\u003c/sub\\u003ePBDE concentrations of the 46\\u0026ndash;60 age population were higher than those of the other two younger groups in all years except 2014. In addition, an increase in half-life with age and an aging-related reduction in the elimination rate could be one of the possible reasons for the age-related increase in POPs in humans (Hardell et al., 2010; Porta et al., 2012).\\u003c/p\\u003e \\u003cp\\u003eWe also found that PBDEs were sex- and congener-specific in our study population. Levels of PBDEs were nearly always lower in females than in males. When stratified by sex, BDE-66, BDE-153, BDE-183, BDE-190 and Σ\\u003csub\\u003e9\\u003c/sub\\u003ePBDE demonstrated a statistically significant difference (p\\u0026thinsp;\\u0026lt;\\u0026thinsp;0.05) between males (higher) and females (lower) in 2013 and 2016. Similar results regarding Σ\\u003csub\\u003e5\\u003c/sub\\u003ePBDE levels were also found in New Zealand (Coakley et al., \\u003cspan citationid=\\\"CR5\\\" class=\\\"CitationRef\\\"\\u003e2018\\u003c/span\\u003e). Toms et al. (2018) also analyzed PBDE exposure in an Australian population and found that the levels of BDE-47, BDE-99, BDE-100, BDE-153 and Σ\\u003csub\\u003e4\\u003c/sub\\u003ePBDE were lower in adult females (aged 31\\u0026ndash;45) than in males from 2002\\u0026ndash;2012. One potential explanation may lie in the females' regular menses, which contribute to the excretion of most of the POPs. On the other hand, women tend to have more body fat distribution than men. As PBDEs are lipophilic, they are more inclined to distribute in body fat than in serum, resulting in lower serum levels of PBDEs in females than in males. In addition, lactating women may excrete some PBDEs through breastfeeding, although further proof is needed. This also reminds us of the exposure risk of children to PBDEs, although it is not discussed in this text.\\u003c/p\\u003e \\u003cp\\u003ePBDEs are a type of POPs that accumulate in organisms and are biomagnified through food chains with elevated levels in top predators (Moon et al. \\u003cspan citationid=\\\"CR24\\\" class=\\\"CitationRef\\\"\\u003e2010\\u003c/span\\u003e). Previous studies have revealed that lipid-rich foods such as eggs, meat and dairy products contribute significantly to human exposure to PBDEs. We found that the intake of eggs, grass carp and catfish in the daily diet of blood donors was positively correlated with PBDEs. Consistent with our research, Chen et al. (2014) found that dietary exposure in their study was a significant route of human PBDE intake and was largely attributed to the consumption of aquatic foods. A study in Korean seafood between 2005 and 2017 also found elevated PBDE concentrations in fatty fish, such as herring, mackerel, and tuna (Choi et al., 2021). This may be because fatty fish are at the upper layer of the food chain, which easily produces a bioamplification effect and causes PBDEs to accumulate in the external environment, thus entering the human body. On the other hand, we also found that daily fruit intake was negatively correlated with PBDE levels. One possibility is that due to lipophilicity, bioaccumulation and biomagnification, PBDEs may accumulate in animals through the food chain, while plants accumulate it to a lesser extent.\\u003c/p\\u003e \\u003cp\\u003eMost temporal trend studies are performed on samples from different individuals from different years or using pooled samples, which might obscure the variation between individuals and accordingly the temporal trend. To the best of our knowledge, we were the first study that actually able to follow the same donor\\u0026rsquo;s serum PBDEs concentrations over a 4-year period. However, several limitations and considerations apply to the evaluation of our present study. First, BDE-209 was not detected in our study, which is one of the main BFRs still being produced and widely used in China. Therefore, we are unable to obtain the exposure trend of BDE-209 in recent years. Second, we only analyzed 132 serum samples collected from 33 donors (repeated sampling of the same individuals over the last 4 years), and the small sample size may limit our power to detect a significant trend over time.\\u003c/p\\u003e\"},{\"header\":\"5. Conclusion\",\"content\":\"\\u003cp\\u003eOur present study focused on determining the levels of 9 PBDE congeners in individual serum samples collected from 2013 to 2016 from blood donors in the Wuxi area. Based on these results, an overall temporal PBDE trend was observed, demonstrating that PBDE levels in the Wuxi area declined between 2013 and 2014 and then increased again after 2014. We also found that PBDEs were sex- and congener-specific in our study population, especially BDE-66, BDE-153, BDE-183, BDE-190 and Σ\\u003csub\\u003e9\\u003c/sub\\u003ePBDE. Moreover, we found that daily dietary intake was related to PBDE exposure. One aspect PBDE congeners are very persistent in the environment and in biota and may negatively affect human health, what is worse, as deca-BDE is still produced and used in China, follow-up studies will be required to improve our understanding of the behaviors of PBDE isomers in humans and the exposure levels.\\u003c/p\\u003e\"},{\"header\":\"Declarations\",\"content\":\"\\u003cp\\u003e\\u003cstrong\\u003eAcknowledgments\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eWe acknowledge the participants for providing serum samples, the staff of Blood Centre for collecting and saving biological samples, and the research team for collecting and analyzing the data.\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eFounding\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThis research was supported by the National Natural Science Foundation of China (Grant No. 81803199), the\\u0026nbsp;Project of Wuxi Commission of Health, China (Grant No. Z201813)\\u0026nbsp;and the\\u0026nbsp;Medical Key\\u0026nbsp;Discipline Program of Wuxi Health Commission (LCZX2021006).\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eCompeting Interests\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThe authors have no relevant financial or non-financial interests to disclose.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eAuthor Contributions\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eAll authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Limei Chen,\\u0026nbsp;Qitao Yin, Lu Xu,\\u0026nbsp;Lu Xu, Minyu Hua, Zhen Zhang, Yuqian Xu, Wei Xia, Huizhong Qian, Jun Hong\\u0026nbsp;and\\u0026nbsp;Jun Jin. The first draft of the manuscript was written by Limei Chen and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.\\u003c/p\\u003e\\n\\u003cp\\u003eThe authors have no conflicts of interest to declare.\\u003c/p\\u003e\"},{\"header\":\"References\",\"content\":\"\\u003col\\u003e\\n\\u003cli\\u003eAkortia E, Okonkwo J, Lupankwa M, et al. A review of sources, levels, and toxicity of polybrominated diphenyl ethers (PBDEs) and their transformation and transport in various environmental compartments. Environmental Reviews, 2016, 24(3).\\u003c/li\\u003e\\n\\u003cli\\u003eCequier E, RM Marc\\u0026eacute;, Becher G, et al. 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J Hazard Mater. 2010, 179:735\\u0026ndash;741.\\u003c/li\\u003e\\n\\u003cli\\u003ePeng F J, Hardy E M, R B\\u0026eacute;ranger, et al. Human exposure to PCBs, PBDEs and bisphenols revealed by hair analysis: A comparison between two adult female populations in China and France. Environmental Pollution, 2020, 267:115425.\\u003c/li\\u003e\\n\\u003cli\\u003eParry E, Zota A R, Park J S, et al. Polybrominated diphenyl ethers (PBDEs) and hydroxylated PBDE metabolites (OH-PBDEs): A six-year temporal trend in Northern California pregnant women. Chemosphere, 2018, 195(MAR.):777-783.\\u003c/li\\u003e\\n\\u003cli\\u003ePorta M, L\\u0026oacute;pez T, Gasull M, et al. Distribution of blood concentrations of persistent organic pollutants in a representative sample of the population of Barcelona in 2006, and comparison with levels in 2002. Sci Total Environ. 2012 Apr 15; 423:151-61.\\u003c/li\\u003e\\n\\u003cli\\u003eSj\\u0026ouml;din A, Jones R S, Wong L Y, et al. Polybrominated Diphenyl Ethers and Biphenyl in Serum: Time Trend Study from the National Health and Nutrition Examination Survey for Years 2005/06 through 2013/14. Environmental Science and Technology, 2019, 53(10):6018-6024.\\u003c/li\\u003e\\n\\u003cli\\u003eSj\\u0026ouml;din A, Mueller J F, Jones R, et al. Serum elimination half-lives adjusted for ongoing exposure of tri-to hexabrominated diphenyl ethers: Determined in persons moving from North America to Australia. Chemosphere, 2020, 248:125905.\\u003c/li\\u003e\\n\\u003cli\\u003eSj\\u0026ouml;din A, Wong LY, Jones RS, et al. Serum concentrations of polybrominated diphenyl ethers (PBDEs) and polybrominated biphenyl (PBB) in the United States population: 2003-2004. Environ Sci Technol. 2008 Feb 15;42(4):1377-84.\\u003c/li\\u003e\\n\\u003cli\\u003eShi Z, Zhang L, Zhao Y, et al. Dietary exposure assessment of Chinese population to tetrabromobisphenol-A, hexabromocyclododecane and decabrominated diphenyl ether: Results of the 5th Chinese Total Diet Study. Environmental Pollution, 2017, 229(oct.):539-547.\\u003c/li\\u003e\\n\\u003cli\\u003eSun M H, Li X H, Xu Y, et al. Exposure to PBDE47 affects mouse oocyte quality via mitochondria dysfunction-induced oxidative stress and apoptosis. Ecotoxicology and Environmental Safety, 2020, 198:110662.\\u003c/li\\u003e\\n\\u003cli\\u003eToms Leisa-Maree L, Sj\\u0026ouml;din Andreas, Hobson Peter, et al. Temporal trends in serum polybrominated diphenyl ether concentrations in the Australian population, 2002\\u0026ndash;2013. Environment International, 2018, 121:357-364.\\u003c/li\\u003e\\n\\u003cli\\u003eVorkamp K, Nielsen F, Kyhl H B, et al. Polybrominated Diphenyl Ethers and Perfluoroalkyl Substances in Serum of Pregnant Women: Levels, Correlations, and Potential Health Implications. Archives of Environmental Contamination \\u0026amp; Toxicology, 2014, 67(1):9-20.\\u003c/li\\u003e\\n\\u003cli\\u003eWang J D, Li J, Shi Z X. Dietary exposure assessment of a nursing mother-infant cohort to legacy and novel brominated flame retardants: Results of a 3-day duplicate diet study in Beijing, China. Chemosphere, 2020, 254:126843.\\u003c/li\\u003e\\n\\u003cli\\u003eWang Hongsheng, Jiang Guanmin, Chen Zhuojia, et al. Concentrations and congener profiles of polybrominated diphenyl ethers (PBDEs) in blood plasma from Hong Kong: Implications for sources and exposure route - ScienceDirect. Journal of Hazardous Materials, 2013, 261(13):253-259.\\u003c/li\\u003e\\n\\u003cli\\u003eWu Zhineng, He Chang, Han Wei, et al. Exposure pathways, levels and toxicity of polybrominated diphenyl ethers in humans: A review \\u0026ndash; Science Direct. Environmental Research, 2020, Aug;187:109531.\\u003c/li\\u003e\\n\\u003cli\\u003eXu B, Wu M, Wang M, et al. Polybrominated diphenyl ethers (PBDEs) and hydroxylated PBDEs in human serum from Shanghai, China: a study on their presence and correlations. Environmental Science \\u0026amp; Pollution Research, 2018 Feb;25(4):3518-3526.\\u003c/li\\u003e\\n\\u003cli\\u003eZhao XZ, Yang XD, Du YL, et al. Polybrominated diphenyl ethers in serum from residents living in a brominated flame retardant production area: Occurrence, influencing factors, and relationships with thyroid and liver function - ScienceDirect. Environmental Pollution, 2020, 270.\\u003c/li\\u003e\\n\\u003cli\\u003eZhineng Wu, Chang He, Wei Han, et al. Exposure pathways, levels and toxicity of polybrominated diphenyl ethers in humans: A review. Environmental Research, 2020, 187: 109531.\\u003c/li\\u003e\\n\\u003c/ol\\u003e\"},{\"header\":\"Tables\",\"content\":\"\\u003cp\\u003eTables are available in the Supplementary Files section.\\u003c/p\\u003e\"}],\"fulltextSource\":\"\",\"fullText\":\"\",\"funders\":[],\"hasAdminPriorityOnWorkflow\":false,\"hasManuscriptDocX\":true,\"hasOptedInToPreprint\":true,\"hasPassedJournalQc\":\"\",\"hasAnyPriority\":false,\"hideJournal\":false,\"highlight\":\"\",\"institution\":\"\",\"isAcceptedByJournal\":true,\"isAuthorSuppliedPdf\":false,\"isDeskRejected\":\"\",\"isHiddenFromSearch\":false,\"isInQc\":false,\"isInWorkflow\":true,\"isPdf\":false,\"isPdfUpToDate\":true,\"isWithdrawnOrRetracted\":false,\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"environmental-science-and-pollution-research\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":false,\"externalIdentity\":\"espr\",\"sideBox\":\"Learn more about [Environmental Science and Pollution Research](https://www.springer.com/journal/11356)\",\"snPcode\":\"11356\",\"submissionUrl\":\"https://submission.nature.com/new-submission/11356/3\",\"title\":\"Environmental Science and Pollution Research\",\"twitterHandle\":\"\",\"acdcEnabled\":true,\"dfaEnabled\":true,\"editorialSystem\":\"em\",\"reportingPortfolio\":\"Springer Hybrid\",\"inReviewEnabled\":true,\"inReviewRevisionsEnabled\":false},\"keywords\":\"Human biomonitoring, Polybrominated diphenyl ethers, Time trend, Human serum\",\"lastPublishedDoi\":\"10.21203/rs.3.rs-2274407/v1\",\"lastPublishedDoiUrl\":\"https://doi.org/10.21203/rs.3.rs-2274407/v1\",\"license\":{\"name\":\"CC BY 4.0\",\"url\":\"https://creativecommons.org/licenses/by/4.0/\"},\"manuscriptAbstract\":\"\\u003cp\\u003ePolybrominated diphenyl ethers (PBDEs) have been used as brominated flame retardants worldwide and are correlated with extensive environmental pollution and human health concerns. This study aims to analyze the concentrations of PBDEs and to evaluate their temporal trends among a population of blood donors over a four-year period. Nine PBDE congeners were quantified in serum samples by gas chromatography with mass spectrometry (GC‒MS). The median concentrations of Σ\\u003csub\\u003e9\\u003c/sub\\u003ePBDEs in each year were 33.46, 29.75, 30.85 and 35.02 ng/g lipid, respectively. Most of the PBDE congeners showed a downward trend from 2013 to 2014 and then increased after 2014. No correlations between age and PBDE congener concentrations were observed, while concentrations of each congener and Σ\\u003csub\\u003e9\\u003c/sub\\u003ePBDE were nearly always lower in females than in males, especially in BDE-66, BDE-153, BDE-183, BDE-190 and Σ\\u003csub\\u003e9\\u003c/sub\\u003ePBDE. We also found that the intake of fish, fruit and eggs in the daily diet was related to the exposure level of PBDEs. Our results suggest that, as deca-BDE is still produced and used in China, diet is an important exposure pathway for PBDEs, and follow-up studies will be required to improve our understanding of the behaviors of PBDE isomers in humans and the exposure levels.\\u003c/p\\u003e\",\"manuscriptTitle\":\"Serum PBDEs exposure and influence factors in blood donors of Wuxi adults from 2013 to 2016\",\"msid\":\"\",\"msnumber\":\"\",\"nonDraftVersions\":[{\"code\":1,\"date\":\"2023-01-13 20:35:13\",\"doi\":\"10.21203/rs.3.rs-2274407/v1\",\"editorialEvents\":[{\"type\":\"communityComments\",\"content\":0},{\"type\":\"reviewerAgreed\",\"content\":\"\",\"date\":\"2023-01-11T10:00:12+00:00\",\"index\":0,\"fulltext\":\"\"},{\"type\":\"reviewersInvited\",\"content\":\"\",\"date\":\"2023-01-11T09:36:12+00:00\",\"index\":\"\",\"fulltext\":\"\"},{\"type\":\"editorInvited\",\"content\":\"Environmental Science and Pollution Research\",\"date\":\"2023-01-03T15:50:14+00:00\",\"index\":\"\",\"fulltext\":\"\"},{\"type\":\"editorAssigned\",\"content\":\"\",\"date\":\"2022-12-09T04:15:34+00:00\",\"index\":\"\",\"fulltext\":\"\"},{\"type\":\"submitted\",\"content\":\"Environmental Science and Pollution Research\",\"date\":\"2022-12-06T03:26:24+00:00\",\"index\":\"\",\"fulltext\":\"\"}],\"status\":\"published\",\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"environmental-science-and-pollution-research\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":false,\"externalIdentity\":\"espr\",\"sideBox\":\"Learn more about [Environmental Science and Pollution Research](https://www.springer.com/journal/11356)\",\"snPcode\":\"11356\",\"submissionUrl\":\"https://submission.nature.com/new-submission/11356/3\",\"title\":\"Environmental Science and Pollution Research\",\"twitterHandle\":\"\",\"acdcEnabled\":true,\"dfaEnabled\":true,\"editorialSystem\":\"em\",\"reportingPortfolio\":\"Springer Hybrid\",\"inReviewEnabled\":true,\"inReviewRevisionsEnabled\":false}}],\"origin\":\"\",\"ownerIdentity\":\"993a2978-904d-4da4-bac1-f2be1b3b2ed6\",\"owner\":[],\"postedDate\":\"January 13th, 2023\",\"published\":true,\"recentEditorialEvents\":[],\"rejectedJournal\":[],\"revision\":\"\",\"amendment\":\"\",\"status\":\"published-in-journal\",\"subjectAreas\":[],\"tags\":[],\"updatedAt\":\"2023-10-16T20:34:39+00:00\",\"versionOfRecord\":{\"articleIdentity\":\"rs-2274407\",\"link\":\"https://doi.org/10.1007/s11356-023-26802-y\",\"journal\":{\"identity\":\"environmental-science-and-pollution-research\",\"isVorOnly\":false,\"title\":\"Environmental Science and Pollution Research\"},\"publishedOn\":\"2023-04-14 20:26:41\",\"publishedOnDateReadable\":\"April 14th, 2023\"},\"versionCreatedAt\":\"2023-01-13 20:35:13\",\"video\":\"\",\"vorDoi\":\"10.1007/s11356-023-26802-y\",\"vorDoiUrl\":\"https://doi.org/10.1007/s11356-023-26802-y\",\"workflowStages\":[]},\"version\":\"v1\",\"identity\":\"rs-2274407\",\"journalConfig\":\"researchsquare\"},\"__N_SSP\":true},\"page\":\"/article/[identity]/[[...version]]\",\"query\":{\"redirect\":\"/article/rs-2274407\",\"identity\":\"rs-2274407\",\"version\":[\"v1\"]},\"buildId\":\"_2-kVJe1T_tPrBINL-cwx\",\"isFallback\":false,\"isExperimentalCompile\":false,\"dynamicIds\":[84888],\"gssp\":true,\"scriptLoader\":[]}","source_license":"CC-BY-4.0","license_restricted":false}